The need for ambulatory emergency oncology: exemplified by the management of immune checkpoint inhibitor toxicity.

Cancer patients seeking emergency care can be vulnerable in increasingly overcrowded Emergency Departments and timely delivery of care is often aspirational rather than reality in many acute care systems. Ambulatory emergency care and its various international models are recognized as contributing to the safety and sustainability of emergency care services. This schema can logically be extended to the emergency oncology setting. The recent proliferation of immune checkpoint inhibitors (ICIs) has led to another opportunity for the management of oncologic complications in the ambulatory emergency care setting. More nuanced risk stratification of currently perceived high-risk toxicities may also afford the opportunity to personalize acute management. Virtual wards, which predominantly provide virtual monitoring only, and hospital at home services, which provide more comprehensive in-person assessment and interventions, may be well suited to supporting care for ICI toxicity alongside hospital-based assessment. Emergency management guidelines for immune-mediated toxicities will increasingly need to be both pragmatic and deliverable, especially as larger numbers of patients will present outside cancer centers. Identifying and modelling those suitable for emergency ambulatory care is integral to achieving this.

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.

Characterization of older adults with cancer seeking acute emergency department care: A prospective observational study.

INTRODUCTION: Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED with active cancer. MATERIALS AND METHODS: Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017. RESULTS: Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics. DISCUSSION: We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.

Palliative Care Needs and Clinical Outcomes of Patients with Advanced Cancer in the Emergency Department.

Background: Older adults with cancer use the emergency department (ED) for acute concerns. Objectives: Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED. Design: A planned secondary data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data. Settings/Subjects: Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States. Measurements: Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status. Results: Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54-71) years. A small proportion of them were receiving palliative (6.5% [95% confidence interval; CI 3.0-7.6]; p = 0.005) and hospice (1.3% [95% CI 1.0-3.2]; p = 0.52) care and had a higher 30-day mortality rate (8.3%, [95% CI 6.2-10.4]). Conclusions: Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care.

Outcomes of Patients with COVID-19 from a Specialized Cancer Care Emergency Room.

PURPOSE: Our goal was to identify discrete clinical characteristics associated with safe discharge from an emergency department/urgent care for patients with a history of cancer and concurrent COVID-19 infection during the SARS-CoV-2 pandemic and prior to widespread vaccination. PATIENTS AND METHODS: We retrospectively analyzed 255 adult patients with a history of cancer who presented to Memorial Sloan Kettering Cancer Center (MSKCC) urgent care center (UCC) from March 1, 2020 to May 31, 2020 with concurrent COVID-19 infection. We evaluated associations between patient characteristics and 30-day mortality from initial emergency department (ED) or urgent care center (UCC) visit and the absence of a severe event within 30 days. External validation was performed on a retrospective data from 29 patients followed at Fred Hutchinson Cancer Research Center that presented to the local emergency department. A late cohort of 108 additional patients at MSKCC from June 1, 2020 to January 31, 2021 was utilized for further validation. RESULTS: In the MSKCC cohort, 30-day mortality and severe event rate was 15% and 32% respectively. Using stepwise regression analysis, elevated BUN and glucose, anemia, and tachypnea were selected as the main predictors of 30-day mortality. Conversely, normal albumin, BUN, calcium, and glucose, neutrophil-lymphocyte ratio <3, lack of (severe) hypoxia, lack of bradycardia or tachypnea, and negative imaging were selected as the main predictors of an uneventful course as defined as a Lack Of a Severe Event within Thirty Days (LOSETD). Utilizing this information, we devised a tool to predict 30-day mortality and LOSETD which achieved an area under the operating curve (AUC) of 79% and 74% respectively. Similar estimates of AUC were obtained in an external validation cohort. A late cohort at MSKCC was consistent with the prior, albeit with a lower AUC. CONCLUSION: We identified easily obtainable variables that predict 30-day mortality and the absence of a severe event for patients with a history of cancer and concurrent COVID-19. This has been translated into a bedside tool that the clinician may utilize to assist disposition of this group of patients from the emergency department or urgent care setting.

Observation unit use among patients with cancer following emergency department visits: Results of a multicenter prospective cohort from CONCERN.

PURPOSE: Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED. METHODS: We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay. RESULTS: Of 1051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6-19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 h. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index. CONCLUSION: In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.

Cancer pain management in the emergency department: a multicenter prospective observational trial of the Comprehensive Oncologic Emergencies Research Network (CONCERN).

PURPOSE: Many patients with cancer seek care for pain in the emergency department (ED). Prospective research on cancer pain in this setting has historically been insufficient. We conducted this study to describe the reported pain among cancer patients presenting to the ED, how pain is managed, and how pain may be associated with clinical outcomes. METHODS: We conducted a multicenter cohort study on adult patients with active cancer presenting to 18 EDs in the USA. We reported pain scores, response to medication, and analgesic utilization. We estimated the associations between pain severity, medication utilization, and the following outcomes: 30-day mortality, 30-day hospital readmission, and ED disposition. RESULTS: The study population included 1075 participants. Those who received an opioid in the ED were more likely to be admitted to the hospital and were more likely to be readmitted within 30 days (OR 1.4 (95% CI: 1.11, 1.88) and OR 1.56 (95% CI: 1.17, 2.07)), respectively. Severe pain at ED presentation was associated with increased 30-day mortality (OR 2.30, 95% CI: 1.05, 5.02), though this risk was attenuated when adjusting for clinical factors (most notably functional status). CONCLUSIONS: Patients with severe pain had a higher risk of mortality, which was attenuated when correcting for clinical characteristics. Those patients who required opioid analgesics in the ED were more likely to require admission and were more at risk of 30-day hospital readmission. Future efforts should focus on these at-risk groups, who may benefit from additional services including palliative care, hospice, or home-health services.

Emergency management of immune-related toxicity.

PURPOSE OF REVIEW: Emergency presentations in patients treated with immune checkpoint inhibitors (ICIs) are a clinical challenge. Clinicians need to be vigilant in diagnosing and treating immune-mediated toxicities. In this review, we consider the approach to managing an acutely unwell patient being treated with ICIs presenting as an emergency. RECENT FINDINGS: A minority of acutely unwell patients treated with ICIs will have an immune-mediated toxicity. Early recognition and intervention in those with immune-mediated toxicity can reduce the duration and severity of the complications. The use of early immunosuppressive agents along corticosteroid therapy may improve outcomes in patients with life-threatening immune-mediated toxicity. SUMMARY: Individualized management of immune-mediated toxicities is a key challenge for emergency oncology services; this has become part of routine cancer care.

Ambulatory emergency oncology: A key tenet of future emergency oncology care.

Ambulatory emergency oncology The challenges of emergency oncology alongside its increasing financial burden have led to an interest in developing optimal care models for meeting patients' needs. Ambulatory care is recognised as a key tenet in ensuring the safety and sustainability of acute care services. Increased access to ambulatory care has successfully reduced ED utilisation and improved clinical outcomes in high-risk non-oncological populations. Individualised management of acute cancer presentations is a key challenge for emergency oncology services so that it can mirror routine cancer care. There are an increasing number of acute cancer presentations, such as low-risk febrile neutropenia and incidental pulmonary embolism, that can be risk assessed for care in an emergency ambulatory setting. Modelling of ambulatory emergency oncology services will be dependent on local service deliveries and pathways, but are key for providing high quality, personalised and sustainable emergency oncology care. These services will also be at the forefront of much needed emergency oncology to define the optimal management of ambulatory-sensitive presentations.

Validation of the Emergency Severity Index (Version 4) for the Triage of Adult Emergency Department Patients With Active Cancer.

BACKGROUND: Patients with active cancer account for a growing percentage of all emergency department (ED) visits and have a unique set of risks related to their disease and its treatments. Effective triage for this population is fundamental to facilitating their emergency care. OBJECTIVES: We evaluated the validity of the Emergency Severity Index (ESI; version 4) triage tool to predict ED-relevant outcomes among adult patients with active cancer. METHODS: We conducted a prespecified analysis of the observational cohort established by the National Cancer Institute-supported Comprehensive Oncologic Emergencies Research Network's multicenter (18 sites) study of ED visits by patients with active cancer (N = 1075). We used a series of χ2 tests for independence to relate ESI scores with 1) disposition, 2) ED resource use, 3) hospital length of stay, and 4) 30-day mortality. RESULTS: Among the 1008 subjects included in this analysis, the ESI distribution skewed heavily toward high acuity (>95% of subjects had an ESI level of 1, 2, or 3). ESI was significantly associated with patient disposition and ED resource use (p values < 0.05). No significant associations were observed between ESI and the non-ED based outcomes of hospital length of stay or 30-day mortality. CONCLUSION: ESI scores among ED patients with active cancer indicate higher acuity than the general ED population and are predictive of disposition and ED resource use. These findings show that the ESI is a valid triage tool for use in this population for outcomes directly relevant to ED care.

Analysis of Diagnoses, Symptoms, Medications, and Admissions Among Patients With Cancer Presenting to Emergency Departments.

Importance: Better understanding of the emergency care needs of patients with cancer will inform outpatient and emergency department (ED) management. Objective: To provide a benchmark description of patients who present to the ED with active cancer. Design, Setting, and Participants: This multicenter prospective cohort study included 18 EDs affiliated with the Comprehensive Oncologic Emergencies Research Network (CONCERN). Of 1564 eligible patients, 1075 adults with active cancer were included from February 1, 2016, through January 30, 2017. Data were analyzed from February 1 through August 1, 2018. Main Outcomes and Measures: The proportion of patients reporting symptoms (eg, pain, nausea) before and during the ED visit, ED and outpatient medications, most common diagnoses, and suspected infection as indicated by ED antibiotic administration. The proportions observed, admitted, and with a hospital length of stay (LOS) of no more than 2 days were identified. Results: Of 1075 participants, mean (SD) age was 62 (14) years, and 51.8% were female. Seven hundred ninety-four participants (73.9%; 95% CI, 71.1%-76.5%) had undergone cancer treatment in the preceding 30 days; 674 (62.7%; 95% CI, 59.7%-65.6%) had advanced or metastatic cancer; and 505 (47.0%; 95% CI, 43.9%-50.0%) were 65 years or older. The 5 most common ED diagnoses were symptom related. Of all participants, 82 (7.6%; 95% CI, 6.1%-9.4%) were placed in observation and 615 (57.2%; 95% CI, 54.2%-60.2%) were admitted; 154 of 615 admissions (25.0%; 95% CI, 21.7%-28.7%) had an LOS of 2 days or less (median, 3 days; interquartile range, 2-6 days). Pain during the ED visit was present in 668 patients (62.1%; 95% CI, 59.2%-65.0%; mean [SD] pain score, 6.4 [2.6] of 10.0) and in 776 (72.2%) during the prior week. Opioids were administered in the ED to 228 of 386 patients (59.1%; 95% CI, 18.8%-23.8%) with moderate to severe ED pain. Outpatient opioids were prescribed to 368 patients (47.4%; 95% CI, 3.14%-37.2%) of those with pre-ED pain, including 244 of 428 (57.0%; 95% CI, 52.2%-61.8%) who reported quite a bit or very much pain. Nausea in the ED was present in 336 (31.3%; 95% CI, 28.5%-34.1%); of these, 160 (47.6%; 95% CI, 12.8%-17.1%) received antiemetics in the ED. Antibiotics were administered in the ED to 285 patients (26.5%; 95% CI, 23.9%-29.2%). Of these, 209 patients (73.3%; 95% CI, 17.1%-21.9%) were admitted compared with 427 of 790 (54.1%; 95% CI, 50.5%-57.6%) not receiving antibiotics. Conclusions and Relevance: This initial prospective, multicenter study profiling patients with cancer who were treated in the ED identifies common characteristics in this patient population and suggests opportunities to optimize care before, during, and after the ED visit. Improvement requires collaboration between specialists and emergency physicians optimizing ED use, improving symptom control, avoiding unnecessary hospitalizations, and appropriately stratifying risk to ensure safe ED treatment and disposition of patients with cancer.

A Population-Based Assessment of Emergency Department Observation Status for Older Adults With Cancer.

Background: Hospitals' use of observation status for patients with cancer presenting to the emergency department (ED) is not well understood. This model of care delivery may be a viable alternative to inpatient admission for patients with cancer presenting with certain conditions. Our objective was to assess the use of observation status among Medicare beneficiaries with and without cancer. Methods: Population-based SEER-Medicare data were used to assess differences in the use of observation status between Medicare beneficiaries aged ≥66 years with and without cancer using a matched analysis (n=151,183 per cohort). We assessed the ratio of observation unit use to inpatient admission, between cancer and noncancer cohorts, and for patients diagnosed with breast, colon, lung, and prostate cancers. Poisson regression models were used to calculate observation rate estimates and 95% CIs while adjusting for selected patient characteristics. Results: When considering the volume of hospitalizations, observation status is used less frequently among beneficiaries with cancer than those without (43 vs 69 observation status visits per 1,000 inpatient admissions, respectively). The estimated observation rate per 1,000 inpatient admissions was higher for beneficiaries aged <75 years versus those aged ≥75 years, those with a Charlson comorbidity index of 0 vs 1 or ≥2, and those without a prior hospitalization versus those with ≥1 prior hospitalizations. Patients with breast and prostate cancers had higher adjusted and unadjusted observation rates per 1,000 inpatient admissions compared with those with colon and lung cancers. Conclusions: Observation status is used proportionately less for beneficiaries with cancer than those without. There may be opportunities to develop standards for ED staff to manage certain conditions for patients with cancer in observation status, and to reserve hospital resources for those who need it most.

Impact of observation status on hospital use for patients with cancer.

PURPOSE: For patients with cancer, the impact of observation status on hospital and patient outcomes is not well understood. Our objective was to assess the impact that an observation unit had on hospital use for patients with cancer who presented to the Urgent Care Center at a comprehensive cancer center. METHODS: We assessed the proportion of Urgent Care Center visits that resulted in an admission to the hospital at a comprehensive cancer center, before (July 9, 2012-December 31, 2012) versus after (July 9, 2013-December 31, 2013) implementation of the observation unit. We also assessed differences in length of stay and stratified the data by presenting complaint. RESULTS: During each 6-month study interval, there were more than 10,000 patient visits to the Urgent Care Center, representing approximately 6,000 unique patients. Fewer visits resulted in an inpatient admission postimplementation (47%) compared with preimplementation (50%). The duration of hospital stay for admitted patients was higher in the post period (median 108 hours) than in the pre period (median 96 hours). Alternatively, the proportion of hospital admissions with a length of stay less than 24 hours was lower in the post period (pre: 7%; post: 5%). Lower admission rates postimplementation were observed for patients who presented with fluid and electrolyte disorders, nausea and vomiting, syncope, and chest pain. CONCLUSION: We observed reductions in hospital use for patients with cancer related to an observation unit in a comprehensive cancer center. Adoption of this approach for this patient population has the potential to reduce hospital use, which is of interest to hospitals, payers, and patients.

ß-Amyloid inhibits E-S potentiation through suppression of cannabinoid receptor 1-dependent synaptic disinhibition.

It has been widely reported that ß-amyloid peptide (Aß) blocks long-term potentiation (LTP) of hippocampal synapses. Here, we show evidence that Aß more potently blocks the potentiation of excitatory postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition. During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aß prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aß can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.