Implementation of a Front-End Split-Flow Model to Promote Performance in an Urban Academic Emergency Department.

BACKGROUND: In an urban academic emergency department (ED), a front-end split-flow model, which entailed deployment of an attending-physician intake model, implementation of a 16-bed clinic decision unit, expanded point-of-care (POC) testing, and dedicated ED transportation services, was created. METHODS: A retrospective, observational, pre-post intervention comparison study was conducted at a large academic urban hospital with 74,000 ED annual visits that serves as a Level 2 Trauma Center. The new flow model was implemented in April 2013, coincident with the opening of a new ED space. RESULTS: During the six-month pre- (July 2012-December 2012) and postimplementation (July 2013-December 2013) periods, there were 17,307 and 27,443, respectively, walk-in encounters during the intake times. Despite this 59% increase and a 35% increase in overall ED patient census, implementation of the innovative novel process redesign resulted in a clinically meaningful reduction (median minutes pre vs. post and one-year post) in (1) overall length of stay (LOS) for all walk-ins (220 vs. 175 and 140), discharged (216 vs. 170 and 140), and inpatient admissions (249 vs. 217 and 181); (2) door-to-physician time (minutes) (54 vs. 15 and 12); and (3) left without being seen (LWBS) rates (5.5% vs. 0.5% and 0.0%). The left before visit complete (LBVC) rates were 0.8% vs. 1.1% and 0.6%. The average total relative value unit (RVU) per patient discharged from intake was 2.31. During the pre-post analysis periods, no significant increase in reported safety events were identified (10 vs. 9 per 1,000 patient encounters). CONCLUSION: Implementation of a novel multifaceted process redesign including an attending physician-driven intake model had a clinically positive impact on ED flow. Validation of this model should be conducted in other practice settings.

Synergistic Toxicities from Multiple Therapies for Synchronous Malignancies.

Patients may present with multiple malignancies in the setting of particular environmental and occupational exposures. These patients often require combination systemic therapy, which has not yet been studied for concurrent use. While toxicities for specific chemotherapies and immunotherapies may be well known, the possibility of exaggerated toxicity due to combination therapy exists and is understudied. Several trials are underway that may shed further light on how combination therapies affect patient toxicity. This case report outlines the unfortunate development of severe edema and rash, refractory to traditional methods of management, from combining immunotherapy and chemotherapy.

NKX3.1 homeodomain protein binds to topoisomerase I and enhances its activity.

The prostate-specific homeodomain protein NKX3.1 is a tumor suppressor that is commonly down-regulated in human prostate cancer. Using an NKX3.1 affinity column, we isolated topoisomerase I (Topo I) from a PC-3 prostate cancer cell extract. Topo I is a class 1B DNA-resolving enzyme that is ubiquitously expressed in higher organisms and many prokaryotes. NKX3.1 interacts with Topo I to enhance formation of the Topo I-DNA complex and to increase Topo I cleavage of DNA. The two proteins interacted in affinity pull-down experiments in the presence of either DNase or RNase. The NKX3.1 homeodomain was essential, but not sufficient, for the interaction with Topo I. NKX3.1 binding to Topo I occurred independently of the Topo I NH2-terminal domain. The binding of equimolar amounts of Topo I to NKX3.1 caused displacement of NKX3.1 from its cognate DNA recognition sequence. Topo I activity in prostates of Nkx3.1+/- and Nkx3.1-/- mice was reduced compared with wild-type mice, whereas Topo I activity in livers, where no NKX3.1 is expressed, was independent of Nkx3.1 genotype. Endogenous Topo I and NKX3.1 could be coimmunoprecipitated from LNCaP cells, where NKX3.1 and Topo I were found to colocalize in the nucleus and comigrate within the nucleus in response to either gamma-irradiation or mitomycin C exposure, two DNA-damaging agents. This is the first report that a homeodomain protein can modify the activity of Topo I and may have implications for organ-specific DNA replication, transcription, or DNA repair.

Cardiac sodium channel blockade after an intentional ingestion of lacosamide, cyclobenzaprine, and levetiracetam: Case report.

CONTEXT: Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose. CASE DETAILS: A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 µg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam concentration was 22.7 µg/mL (therapeutic: 12-46 µg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae. DISCUSSION: The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity.

Tumor cells thrive in a hypoxic microenvironment with an acidic extracellular pH. To survive in this harsh environment, tumor cells must exhibit a dynamic cytosolic pH regulatory system. We hypothesize that vacuolar H(+)-ATPases (V-ATPases) that normally reside in acidic organelles are also located at the cell surface, thus regulating cytosolic pH and exacerbating the migratory ability of metastatic cells. Immunocytochemical data revealed for the first time that V-ATPase is located at the plasma membrane of human breast cancer cells: prominent in the highly metastatic and inconspicuous in the lowly metastatic cells. The V-ATPase activities in isolated plasma membranes were greater in highly than in lowly metastatic cells. The proton fluxes via V-ATPase evaluated by fluorescence spectroscopy in living cells were greater in highly than in lowly metastatic cells. Interestingly, lowly metastatic cells preferentially used the ubiquitous Na(+)/H(+) exchanger and HCO(3)(-)-based H(+)-transporting mechanisms, whereas highly metastatic cells used plasma membrane V-ATPases. The highly metastatic cells were more invasive and migratory than the lowly metastatic cells. V-ATPase inhibitors decreased the invasion and migration in the highly metastatic cells. Altogether, these data indicate that V-ATPases located at the plasma membrane are involved in the acquisition of a more metastatic phenotype.