Rapid Response EEG: Current State and Future Directions.

PURPOSE OF REVIEW: To critically appraise the literature on the application, methods, and advances in emergency electroencephalography (EEG). RECENT FINDINGS: The development of rapid EEG (rEEG) technologies and other reduced montage approaches, along with advances in machine learning over the past decade, has increased the rate and access to EEG acquisition. These achievements have made EEG in the emergency setting a practical diagnostic technique for detecting seizures, suspected nonconvulsive status epilepticus (NCSE), altered mental status, stroke, and in the setting of sedation. Growing evidence supports using EEG to expedite medical decision-making in the setting of suspected acute neurological injury. This review covers approaches to acquiring EEG in the emergency setting in the adult and pediatric populations. We also cover the clinical impact of this data, the time associated with emergency EEG, and the costs of acquiring EEG in these settings. Finally, we discuss the advances in artificial intelligence for rapid electrophysiological interpretation.

Evaluating Cancer Pain Characteristics and Treatment Factors in the Emergency Department: A Retrospective Cohort Study.

Objectives: To identify patient characteristics and treatment factors of patients presenting to the emergency department (ED) with cancer-related pain that may affect patient outcomes. Methods: We conducted a retrospective cohort study to evaluate adult patients with active cancer, who presented to the ED with a chief complaint of pain between June first, 2012 and January first, 2016. We utilized multivariable logistic regression to evaluate the association of several exposure variables, including disease and demographic characteristics, primary pain site, and treatment methods, on ED disposition and revisit rate. Results: We included 483 patients with active cancer with a chief complaint of pain. Patients with severe pain on arrival tended to be younger than those who did not present with severe pain (median: 58 vs 62 respectively, OR 8.0 p < 0.01). Patients with high ECOG scores (3-4) with severe pain on arrival (≥7 out of 10) had less improvement in their pain than the rest of our cohort (OR 8.4, p < 0.01). Also, those with musculoskeletal pain had significantly less improvement in reported pain than all other pain types (delta pain -2.1 vs -3.4, OR 2.3, p = 0.025) Long delays in initial analgesic administration were associated with increased rates of subsequent admission (OR 3.4) [p = 0.014]. Although opioid analgesics led to greater decreases in pain than non-opioid analgesics, patients treated with opioids were more likely to be admitted (43% vs 34.5% AOR 1.51, p = 0.048). Conclusion: Our study showed that delays in analgesic administration, poor functional status, and the presence of musculoskeletal (MSK) pain significantly influenced outcomes for this patient cohort. These findings suggest the development of specific protocols and tools to address cancer-related pain in the ED may be necessary.

Patients Who Leave the Emergency Department Without Being Seen and Their Follow-Up Behavior: A Retrospective Descriptive Analysis.

BACKGROUND: Past studies suggest that patients who leave without being seen (LWBS) by a physician from a hospital's emergency department (ED) represent a quality and safety concern, and thus LWBS rates have often been used as an ED performance metric. There are few recent studies, however, that have examined the characteristics of the LWBS population at hospitals in the United States. OBJECTIVE: This study describes the LWBS population at a multi-hospital academic health system. METHODS: This was a retrospective study of electronic medical record data from EDs at two academic hospitals with a shared patient population that analyzed all LWBS visits during the 45-month period between July 2012 and March 2016. Demographic and clinical variables, including patient characteristics, chief complaint, acuity, and evidence of ongoing medical care, were assessed. RESULTS: During the study period, 2.4% of patients presenting to the study EDs left without being seen. This population tended to have lower-acuity chief complaints and nearly triple the number of ED visits as the general ED patient; 7.8% sought follow-up care from outpatient clinics and 24.8% returned to the ED within 7 days. Of this latter group, 11.5% were subsequently admitted for inpatient care, representing 0.068% of the total ED census during the study period. CONCLUSIONS: LWBS patients are high ED utilizers who may be effectively targeted by "hotspotting." Our 11.5% admission rate at return after LWBS compares favorably with the overall 20.9% admission rate at the study EDs and represents a small minority of all LWBS visits. Given the paucity of return ED visits after interval clinic encounters, our data suggest that patients who were seen in clinic had their medical complaint adequately resolved on a non-emergent outpatient basis, and that increased LWBS rates may reflect poor access to timely clinic-based care rather than intrinsic systemic issues within the ED.

Systematic Review: Rectal Administration of Medications for Pediatric Procedural Sedation.

BACKGROUND: Per rectum (PR) medication delivery is an alternative to traditional oral (PO), intravenous (IV), or intramuscular (IM) administration of medication for procedural sedation of pediatric emergency department patients. However, many emergency physicians are unfamiliar with its use, and there are no widely adopted guidelines or reviews dedicated to this topic. OBJECTIVE: Our aim was to provide emergency physicians with an overview of PR procedural sedation medications in pediatric patients. METHODS: We performed a PubMed literature search of relevant keywords limited to studies of human subjects published in English between January 1, 1990 and December 31, 2017. We excluded case reports, general review articles, editorial/opinion pieces, correspondence, and abstracts. Two of the authors then conducted a structured review of the selected studies. RESULTS: A total of 315 PubMed citations meeting the search criteria were found. Twenty-eight articles were included for final detailed review. Only 4 of the 28 included studies were conducted in the emergency department setting. A total of 9 different medications have been studied for PR procedural sedation. Sedation effectiveness ranged from 40% to 98%. No life-threatening complications were reported in any of the included clinical trials. Hypoxia was found to occur in up to 10% of those receiving PR sedation. CONCLUSIONS: Pediatric procedural sedation with PR medications appears to be feasible, moderately effective, and safe based on our review of the current literature. However, further studies on its applicability in the emergency department setting are needed.

Synergy of Histone-Deacetylase Inhibitor AR-42 with Cisplatin in Bladder Cancer.

PURPOSE: Cisplatin based chemotherapy regimens form the basis of systemic bladder cancer treatment, although they show limited response rates and efficacy. Recent molecular analysis of bladder cancer revealed a high incidence of mutations in chromatin regulatory genes, suggesting a therapeutic avenue for histone deacetylase inhibitors. We investigated the ability of the novel histone deacetylase inhibitor AR-42 to synergize with cisplatin in preclinical models of bladder cancer. MATERIALS AND METHODS: We assessed the ability of the pan-histone deacetylase inhibitor AR-42 with and without cisplatin to destroy bladder cancer cells by survival and apoptosis assays in vitro, and by growth and differentiation in an in vivo xenograft model. We also assessed the response to the bladder cancer stem cell population by examining the effect of AR-42 on the CD44(+)CD49f(+) population with and without cisplatin. Synergy was calculated using combination indexes. RESULTS: The AR-42 and cisplatin combination synergistically destroyed bladder cancer cells via apoptosis and it influenced tumor growth and differentiation in vivo. When tested in the CD44(+)CD49f(+) bladder cancer stem cell population, AR-42 showed greater efficacy with and without cisplatin. CONCLUSIONS: AR-42 may be an attractive novel histone deacetylase inhibitor with activity against bladder cancer. Its efficacy in bladder cancer stem cells and synergy with cisplatin warrant further clinical investigation. Our in vitro and animal model studies provide preclinical evidence that AR-42 may be administered in conjunction with cisplatin based chemotherapy to improve the treatment of bladder cancer in patients.

Stromal modulation of bladder cancer-initiating cells in a subcutaneous tumor model.

The development of new cancer therapeutics would benefit from incorporating efficient tumor models that mimic human disease. We have developed a subcutaneous bladder tumor regeneration system that recapitulates primary human bladder tumor architecture by recombining benign human fetal bladder stromal cells with SW780 bladder carcinoma cells. As a first step, SW780 cells were seeded in ultra low attachment cultures in order to select for sphere-forming cells, the putative cancer stem cell (CSC) phenotype. Spheroids were combined with primary human fetal stromal cells or vehicle control and injected subcutaneously with Matrigel into NSG mice. SW780 bladder tumors that formed in the presence of stroma showed accelerated growth, muscle invasion, epithelial to mesenchymal transition (EMT), decreased differentiation, and greater activation of growth pathways compared to tumors formed in the absence of fetal stroma. Tumors grown with stroma also demonstrated a greater similarity to typical malignant bladder architecture, including the formation of papillary structures. In an effort to determine if cancer cells from primary tumors could form similar structures in vivo using this recombinatorial approach, putative CSCs, sorted based on the CD44(+)CD49f(+) antigenic profile, were collected and recombined with fetal bladder stromal cells and Matrigel prior to subcutaneous implantation. Retrieved grafts contained tumors that exhibited the same structure as the original primary human tumor. Primary bladder tumor regeneration using human fetal bladder stroma may help elucidate the influences of stroma on tumor growth and development, as well as provide an efficient and accessible system for therapeutic testing.