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The attachment of sugar to proteins and lipids is a basic modification needed for organismal survival, and perturbations in glycosylation cause severe developmental and neurological difficulties. Here, we investigated the neurological consequences of N-glycan populations in the spinal cord of Wt AB and mgat1b mutant zebrafish. Mutant fish have reduced N-acetylglucosaminyltransferase-I (GnT-I) activity as mgat1a remains intact. GnT-I converts oligomannose N-glycans to hybrid N-glycans, which is needed for complex N-glycan production. MALDI-TOF MS profiles identified N-glycans in the spinal cord for the first time and revealed reduced amounts of complex N-glycans in mutant fish, supporting a lesion in mgat1b . Further lectin blotting showed that oligomannose N-glycans were more prevalent in the spinal cord, skeletal muscle, heart, swim bladder, skin, and testis in mutant fish relative to WT AB, supporting lowered GnT- I activity in a global manner. Developmental delays were noted in hatching and in the swim bladder. Microscopic images of caudal primary (CaP) motor neurons of the spinal cord transiently expressing EGFP in mutant fish were abnormal with significant reductions in collateral branches. Further motor coordination skills were impaired in mutant fish. We conclude that identifying the neurological consequences of aberrant N-glycan processing will enhance our understanding of the role of complex N-glycans in development and nervous system health.

Purpose: Ultrasonic propulsion is an investigational procedure for awake patients. Our purpose was to evaluate whether ultrasonic propulsion to facilitate residual kidney stone fragment clearance reduced relapse., Materials and Methods: This multicenter, prospective, open-label, randomized, controlled trial used single block randomization (1:1) without masking. Adults with residual fragments (individually ≤5 mm) were enrolled. Primary outcome was relapse as measured by stone growth, a stone-related urgent medical visit, or surgery by 5 years or study end. Secondary outcomes were fragment passage within 3 weeks and adverse events within 90 days. Cumulative incidence of relapse was estimated using the Kaplan-Meier method. Log-rank test was used to compare the treatment (ultrasonic propulsion) and control (observation) groups., Results: The trial was conducted from May 9, 2015, through April 6, 2024. Median follow-up (interquartile range) was 3.0 (1.8-3.2) years. The treatment group (n = 40) had longer time to relapse than the control group (n = 42; P < .003). The restricted mean time-to-relapse was 52% longer in the treatment group than in the control group (1530 ± 92 days vs 1009 ± 118 days), and the risk of relapse was lower (hazard ratio 0.30, 95% CI 0.13-0.68) with 8 of 40 and 21 of 42 participants, respectively, experiencing relapse. Omitting 3 participants not asked about passage, 24 treatment (63%) and 2 control (5%) participants passed fragments within 3 weeks of treatment. adverse events were mild, transient, and self-resolving, and were reported in 25 treated participants (63%) and 17 controls (40%)., Conclusions: Ultrasonic propulsion reduced relapse and added minimal risk., Clinical Trial Registration No.: NCT02028559.

Purpose: This study reports on a prospective, multicenter, single-arm, clinical trial utilizing the SonoMotion (San Mateo, California) Break Wave lithotripsy (BWL) device to fragment urinary stones., Materials and Methods: Patients with a urinary stone underwent a single treatment of 30 minutes and peak negative pressure of 4.5 to 8 MPa. Subjects were contacted and outcomes assessed at 7, 14, and 35 days after treatment, with clinical follow-up and CT imaging 70 ± 14 days postprocedure. The primary objectives were to assess the safety (hematomas, complications, etc) and effectiveness of BWL (any fragmentation, residual fragments ≤4 mm or ≤2 mm, and completely stone-free rate) as assessed via noncontrast CT-kidneys, ureters, and bladder., Results: Forty-four patients with a ureteral (43%) or renal (57%) stone were treated across 5 centers. Stone fragmentation occurred in 88% of cases; 70% had fragments ≤ 4 and 51% ≤ 2 mm, while 49% were completely stone free on CT; no serious adverse events were reported. Eighty-six percent of patients received either no analgesic medication at all (50%) or minor analgesia (36%). After determining optimal therapy settings, 36 patients were treated and the effectiveness improved exhibiting fragmentation in 92% (33/36), residual fragments ≤ 4 mm in 75% and 58% with fragments ≤ 2 mm with 58% completely stone free. Effectiveness was less in subjects with lower pole stones with 81% fragmentation, 71% having fragments ≤ 4 mm, 29% with fragments ≤ 2 mm, and 29% completely stone free; of distal ureteral stone patients, 89% were completely stone free., Conclusions: BWL offered safe and effective noninvasive stone therapy requiring little to no anesthesia and was carried out successfully in nonoperative environments., Trial Registration: ClinicalTrials.gov identifier: NCT03811171.

Importance: Patients with inequitable access to patient portals frequently present to emergency departments (EDs) for care. Little is known about portal use patterns among ED patients., Objectives: To describe real-time patient portal usage trends among ED patients and compare demographic and clinical characteristics between portal users and nonusers., Design, Setting, and Participants: In this cross-sectional study of 12 teaching and 24 academic-affiliated EDs from 8 health systems in California, Connecticut, Massachusetts, Ohio, Tennessee, Texas, and Washington, patient portal access and usage data were evaluated for all ED patients 18 years or older between April 5, 2021, and April 4, 2022., Exposure: Use of the patient portal during ED visit., Main Outcomes and Measures: The primary outcomes were the weekly proportions of ED patients who logged into the portal, viewed test results, and viewed clinical notes in real time. Pooled random-effects models were used to evaluate temporal trends and demographic and clinical characteristics associated with real-time portal use., Results: The study included 1 280 924 unique patient encounters (53.5% female; 0.6% American Indian or Alaska Native, 3.7% Asian, 18.0% Black, 10.7% Hispanic, 0.4% Native Hawaiian or Pacific Islander, 66.5% White, 10.0% other race, and 4.0% with missing race or ethnicity; 91.2% English-speaking patients; mean [SD] age, 51.9 [19.2] years). During the study, 17.4% of patients logged into the portal while in the ED, whereas 14.1% viewed test results and 2.5% viewed clinical notes. The odds of accessing the portal (odds ratio [OR], 1.36; 95% CI, 1.19-1.56), viewing test results (OR, 1.63; 95% CI, 1.30-2.04), and viewing clinical notes (OR, 1.60; 95% CI, 1.19-2.15) were higher at the end of the study vs the beginning. Patients with active portal accounts at ED arrival had a higher odds of logging into the portal (OR, 17.73; 95% CI, 9.37-33.56), viewing test results (OR, 18.50; 95% CI, 9.62-35.57), and viewing clinical notes (OR, 18.40; 95% CI, 10.31-32.86). Patients who were male, Black, or without commercial insurance had lower odds of logging into the portal, viewing results, and viewing clinical notes., Conclusions and Relevance: These findings suggest that real-time patient portal use during ED encounters has increased over time, but disparities exist in portal access that mirror trends in portal usage more generally. Given emergency medicine's role in caring for medically underserved patients, there are opportunities for EDs to enroll and train patients in using patient portals to promote engagement during and after their visits.

Background: Traditionally, the manufacture of prostheses is time-consuming and labor-intensive. One possible route to improving access and quality of these devices is the digitalizing of the fabrication process, which may reduce the burden of manual labor and bring the potential for automation that could help unblock access to assistive technologies globally., Objectives: To identify where there are gaps in the literature that are creating barriers to decision-making on either appropriate uptake by clinical teams or on the needed next steps in research that mean these technologies can continue on a pathway to maturity., Study Design: Scoping literature review., Methods: A comprehensive search was completed in the following databases: Allied and Complementary Medicine Database, MEDLINE, Embase, Global Health Archive, CINAHL Plus, Cochrane Library, Web of Science, Association for Computing Machinery, Institute of Electrical and Electronics Engineers, and Engineering Village, resulting in 3487 articles to be screened., Results: After screening, 130 lower limb prosthetic articles and 117 upper limb prosthetic articles were included in this review. Multiple limitations in the literature were identified, particularly a lack of long-term, larger-scale studies; research into the training requirements for these technologies and the necessary rectification processes; and a high range of variance of production workflows and materials which makes drawing conclusions difficult., Conclusions: These limitations create a barrier to adequate evidence-based decision-making for clinicians, technology developers, and wider policymakers. Increased collaboration between academia, industry, and clinical teams across more of the pathway to market for new technologies could be a route to addressing these gaps., (Copyright © 2024 International Society for Prosthetics and Orthotics.)

Objectives: The number and distribution of lung ultrasound (LUS) imaging artifacts termed B-lines correlate with the presence of acute lung disease such as infection, acute respiratory distress syndrome (ARDS), and pulmonary edema. Detection and interpretation of B-lines require dedicated training and is machine and operator-dependent. The goal of this study was to identify radio frequency (RF) signal features associated with B-lines in a cohort of patients with cardiogenic pulmonary edema. A quantitative signal indicator could then be used in a single-element, non-imaging, wearable, automated lung ultrasound sensor (LUSS) for continuous hands-free monitoring of lung fluid., Methods: In this prospective study a 10-zone LUS exam was performed in 16 participants, including 12 patients admitted with acute cardiogenic pulmonary edema (mean age 60 ± 12 years) and 4 healthy controls (mean age 44 ± 21). Overall,160 individual LUS video clips were recorded. The LUS exams were performed with a phased array probe driven by an open-platform ultrasound system with simultaneous RF signal collection. RF data were analyzed offline for candidate B-line indicators based on signal amplitude, temporal variability, and frequency spectrum; blinded independent review of LUS images for the presence or absence of B-lines served as ground truth. Predictive performance of the signal indicators was determined with receiving operator characteristic (ROC) analysis with k-fold cross-validation., Results: Two RF signal features-temporal variability of signal amplitude at large depths and at the pleural line-were strongly associated with B-line presence. The sensitivity and specificity of a combinatorial indicator were 93.2 and 58.5%, respectively, with cross-validated area under the ROC curve (AUC) of 0.91 (95% CI = 0.80-0.94)., Conclusion: A combinatorial signal indicator for use with single-element non-imaging LUSS was developed to facilitate continuous monitoring of lung fluid in patients with respiratory illness., (© 2023 American Institute of Ultrasound in Medicine.)

Introduction: Ultrasound-guided peripheral IV catheter (USGIV) insertion is as an effective procedure to establish access in patients with difficult intravenous access (DIVA), a condition frequently encountered in the Emergency Department (ED). This study describes a DIVA quality improvement program focusing on rapid identification of DIVA patients and emergency nurse USGIV training and evaluates its impact on overall frequency of USGIV use and process measures related to quality of patient care., Methods: This is a retrospective cohort study of patients over 18 years of age, presenting to a single, tertiary care hospital between September 1, 2018 and September 30, 2020. Difference-in-difference analysis was used to compare ED process measures pre- and post-implementation of the DIVA Program, and multivariate logistic regression was used to identify associations between patient characteristics and difficult IV access., Results: The frequency of ED encounters associated with USGIV placement more than doubled post-implementation of the DIVA Program, rising from 606 to 1323. There were improved covariate-adjusted time estimates of core ED process measures for encounters associated with USGIV placement post-implementation, including decreases in time to CT with contrast from 4.8 h (95% CI = 4.4-5.2) to 4.1 h (95% CI = 3.8-4.4), pain medications from 2.4 h (95% CI = 2.1-2.6) to 1.8 h (95% CI = 1.6-2.0), IV antibiotics from 3.0 h (95% CI = 2.4-3.7) to 2.1 h (95% CI = 1.5-2.6), and ED length of stay from 6.4 h (95% CI = 6.2-6.6) to 6.0 h (95% CI = 5.9-6.2)., Conclusion: A nurse-focused quality improvement program focused on teaching and promoting USGIV as a modality for managing difficult IV access was associated with increases in USGIV placement and improvements in core process measures related to quality of patient care., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Evidence continues to accumulate that select patients with acute low-risk pulmonary embolism (PE) can be safely discharged from the emergency department. Despite this, outpatient management continues to be uncommon. We report changes in emergency providers' stated preferences on low-risk acute PE management before and after the development and implementation of an institutional clinical pathway and decision tool., Methods: We performed an observational analysis of attending emergency physicians' stated preferences towards the management of low-risk acute PE using survey results before and after the development and implementation of an electronic health record-embedded institutional low-risk acute PE pathway., Results: Attending emergency medicine providers reported feeling more comfortable using PE risk stratification scores to identify dischargeable low-risk PE patients and also reported that they would be more likely to discharge a hypothetical patient with low-risk acute PE., Conclusion: Our results suggest that the implementation of an institutional clinical pathway with integration into the electronic health record was associated with a change in emergency physicians' stated preferences for managing patients with acute low-risk PE in the emergency department. Implementation of an evidence-based standard pathway was associated with increased comfort and familiarity with PE risk stratification, and an increased comfort with and preference for early outpatient management of low-risk PE., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A lack of complex and hybrid types of N-glycans in mice is embryonically lethal due to neural tube maldevelopment. N-acetylglucosaminyltransferase-I (GnT-I; Mgat1 ) catalyzes a required step for converting oligomannose N-glycans into hybrid and complex N-glycans. Unlike mice, zebrafish have two Mgat1a/b genes. Herein, CRISPR/Cas9 technology was used to knockdown GnT-Ib activity in zebrafish, referred to as Mgat1b - / - , to examine the impact of a decrease in complex types of N-glycans on survival and development, and sensory and motor functions. Genotyping verified the occurrence of edited Mgat1b , and LC-ESI-MS and lectin blotting identified higher levels of oligomannose and lower levels of complex N-glycans in Mgat1b - / - relative to Wt AB. The microscopic visualization of developmental stages and locomotor studies using an automated tracking unit and manual touch assays revealed reduced survivability, and delayed motor and sensory functions in Mgat1b - / - . Moreover, embryonic staging linked reduced survivability of Mgat1b - / - to disruption in brain anlagen formation. Birefringence measurements supported delayed skeletal muscle development, which corresponded with motor and sensory function impediments in Mgat1b - / - . Furthermore, GnT-Ib knockdown hindered cardiac activity onset. Collectively, Mgat1b - / - displayed incomplete penetrance and variable expressivity, such that some died in early embryonic development, while others survived to adulthood, albeit, with developmental delays. Thus, the results reveal that reducing the amount of complex-type N-glycans is unfavorable for zebrafish survival and development. Moreover, our results support a better understanding of human congenital disorders of glycosylation.

Enhanced N-glycan branching is associated with cancer, but recent investigations supported the involvement of less processed N-glycans. Herein, we investigated how changes in N-glycosylation influence cellular properties in neuroblastoma (NB) using rat N-glycan mutant cell lines, NB&#95;1(- Mgat1 ), NB&#95;1(- Mgat2 ) and NB&#95;1(- Mgat3 ), as well as the parental cell line NB&#95;1. The two earlier mutant cells have compromised N-acetylglucosaminyltransferase-I (GnT-I) and GnT-II activities. Lectin blotting showed that NB&#95;1(- Mgat3 ) cells had decreased activity of GnT-III compared to NB&#95;1. ESI-MS profiles identified N-glycan structures in NB cells, supporting genetic edits. NB&#95;1(- Mgat1 ) had the most oligomannose N-glycans and the greatest cell invasiveness, while NB&#95;1(- Mgat2 ) had the fewest and least cell invasiveness. The proliferation rate of NB&#95;1 was slightly slower than NB&#95;1(- Mgat3 ), but faster than NB&#95;1(- Mgat1 ) and NB&#95;1(- Mgat2 ). Faster proliferation rates were due to the faster progression of those cells through the G1 phase of the cell cycle. Further higher levels of oligomannose with 6-9 Man residues indicated faster proliferating cells. Human NB cells with higher oligomannose N-glycans were more invasive and had slower proliferation rates. Both rat and human NB cells revealed modified levels of ER chaperones. Thus, our results support a role of oligomannose N-glycans in NB progression; furthermore, perturbations in the N-glycosylation pathway can impact chaperone systems.

Purpose: Advanced imaging examinations of emergently transferred patients (ETPs) are overread to various degrees by receiving institutions. The practical clinical impact of these second opinions has not been studied in the past. The purpose of this study is to determine if emergency radiology overreads change emergency medicine decision making on ETPs in the emergency department (ED)., Methods: All CT and MRI examinations on patients transferred to a level I trauma center during calendar year 2018 were routinely overread by emergency radiologists and discrepancies with the outside report electronically flagged. All discrepant reports compared with the outside interpretations were reviewed by one of four emergency medicine physicians. Comparing the original and final reports, reviewers identified changes in patient management that could be attributed to the additional information contained in the final report. Changes in patient care were categorized as affecting ED management, disposition, follow-up, or consulting services., Results: Over a 12-month period, 5,834 patients were accepted in transfer. Among 5,631 CT or MRI examinations with outside reports available, 669 examinations (12%) had at least one discrepancy in the corresponding outside report. In 219 examinations (33%), ED management was changed by discrepancies noted on the final report; patient disposition was affected in 84 (13%), outpatient follow-up in 54 (8%), and selection of consulting services in 411 (61%), and ED stay was extended in 544 (81%). Discrepant findings affected decision making in 613 of 669 of examinations (92%)., Conclusion: Emergency radiology overreading of transferred patients' advanced imaging examinations provided actionable additional information to emergency medicine physicians in the care of 613 of 669 (92%) examinations with discrepant findings. This added value is worth the effort to design workflows to routinely overread CT and MRI examinations of ETPs., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Our goal was to test transcutaneous focused ultrasound in the form of ultrasonic propulsion and burst wave lithotripsy to reposition ureteral stones and facilitate passage in awake subjects., Materials and Methods: Adult subjects with a diagnosed proximal or distal ureteral stone were prospectively recruited. Ultrasonic propulsion alone or with burst wave lithotripsy was administered by a handheld transducer to awake, unanesthetized subjects. Efficacy outcomes included stone motion, stone passage, and pain relief. Safety outcome was the reporting of associated anticipated or adverse events., Results: Twenty-nine subjects received either ultrasonic propulsion alone (n = 16) or with burst wave lithotripsy bursts (n = 13), and stone motion was observed in 19 (66%). The stone passed in 18 (86%) of the 21 distal ureteral stone cases with at least 2 weeks follow-up in an average of 3.9±4.9 days post-procedure. Fragmentation was observed in 7 of the burst wave lithotripsy cases. All subjects tolerated the procedure with average pain scores (0-10) dropping from 2.1±2.3 to 1.6±2.0 ( P = .03). Anticipated events were limited to hematuria on initial urination post-procedure and mild pain. In total, 7 subjects had associated discomfort with only 2.2% (18 of 820) propulsion bursts., Conclusions: This study supports the efficacy and safety of using ultrasonic propulsion and burst wave lithotripsy in awake subjects to reposition and break ureteral stones to relieve pain and facilitate passage.

Objective: To convene a multi-disciplinary panel to develop a pathway for Emergency Department (ED) patients with suspected nephrolithiasis and then prospectively evaluate its effect on patient care., Materials and Methods: The STONE Pathway was developed and linked to order sets within our Electronic Health Record in April 2019. Records were prospectively reviewed for ED patients who underwent ultrasound or Computerized Tomography (CT) to evaluate suspected nephrolithiasis between January 2019 and August 2019 within our institution. The primary outcome measure was the proportion of patients whose ED CT was low dose (<4 mSv). Secondary outcome measures included receipt of pathway-concordant pain medications and urine strainers. Order set utilization was evaluated as a process measure. Balance measures assessed included repeat ED visits, imaging, hospitalizations, and a urologic clinic visit or surgery within 30 days of discharge., Results: 441 patients underwent ED imaging, of whom 261 (59%) were evaluated for suspected nephrolithiasis. The STONE Pathway was used in 50 (30%) eligible patients. Patients treated with the Pathway were more likely to undergo low-dose CTs (49% vs 23%, P <.001), and receive guideline-concordant pain medications such as NSAIDs (90% vs 62%, P <.001), and were less likely to return to the ED within 30 days (13% vs 2%, P = .01). These measures demonstrated special cause variation following Pathway release., Conclusion: Clinical pathways increase compliance with evidence-based practices for pain control and imaging in nephrolithiasis emergency care and may improve the delivery of value-based care., Competing Interests: DECLARATION OF COMPETING INTEREST Please copy this Conflict-of-Interest form and paste into your word processing software, type in each author and either indicate "no conflict" or specify any conflicts; it will be required that you submit the completed form (with all authors indicated) with the revised manuscript. Please list only conflicts of interest specific to this manuscript., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Tumor development can be promoted/suppressed by certain N-glycans attached to proteins at the cell surface. Here we examined aberrant neuronal properties in 2D and 3D rat neuroblastoma (NB) cell cultures with different N-glycan populations. Lectin binding studies revealed that the engineered N-glycosylation mutant cell line, NB&#95;1(-Mgat1), expressed solely oligomannose N-glycans, and verified that the parental cell line, NB&#95;1, and a previous engineered N-glycosylation mutant, NB&#95;1(-Mgat2), expressed significant levels of higher order N-glycans, complex and hybrid N-glycans, respectively. NB&#95;1 grew faster than mutant cell lines in monolayer and spheroid cell cultures. A 2-fold difference in growth between NB&#95;1 and mutants occurred much sooner in 2D cultures relative to that observed in 3D cultures. Neurites and spheroid cell sizes were reduced in mutant NB cells of 2D and 3D cultures, respectively. Cell invasiveness was highest in 2D cultures of NB&#95;1 cells compared to that of NB&#95;1(-Mgat1). In contrast, NB&#95;1 spheroid cells were much less invasive relative to NB&#95;1(-Mgat1) spheroid cells while they were more invasive than NB&#95;1(-Mgat2). Gelatinase activities supported the ranking of cell invasiveness in various cell lines. Both palladin and HK2 were more abundant in 3D than 2D cultures. Levels of palladin, vimentin and EGFR were modified in a different manner under 2D and 3D cultures. Thus, our results support variations in the N-glycosylation pathway and in cell culturing to more resemble in vivo tumor environments can impact the aberrant cellular properties, particularly cell invasiveness, of NB., Competing Interests: The authors have declared that no competing interest exist.

Objectives:  Traumatic hand injuries present to emergency departments frequently. Pain secondary to these injuries is typically managed with opioids, which may be inadequate and have side effects. Ultrasound (US)-guided forearm nerve blocks have emerged as an alternative modality for patients with acute pain from isolated extremity injuries., Methods:  We performed a non-blinded, consecutive, randomized pragmatic trial of US-guided forearm nerve blocks using medium and long-acting anesthetic versus usual care for a six-day period around July 4th, 2017. Adults who sustained a traumatic or blast injury of their hands were considered. Consecutive emergency department patients were consented, enrolled and randomized into a study group (block) or control (standard care). The study group received a US-guided forearm block using a 50/50 mix of 1% lidocaine and 0.5% bupivacaine. The primary outcome was median pain scores via a 100-point visual analog scale at 15, 60, and 120 minutes after the nerve block compared to the baseline pain score. The secondary outcome was mean morphine equivalents administered., Results:  Sixteen patients were screened and 12 were randomized: six to the treatment group and six to the control group. Median pain reduction from baseline at 15, 60, and 120 minutes in the forearm block group was -35 (IQR=10), -30 (IQR=50), and -20 (IQR=70, versus -5 (IQR=10), -20.5 (IQR=20), -20 (IQR=70) in the control group. At all time points, patient-reported pain scores decreased significantly over baseline in the forearm block group, whereas non-significant reductions in pain scores occurred in the control group., Conclusion: US-guided forearm blocks for acute traumatic hand injuries resulted in greater pain relief when compared to usual care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Vrablik et al.)

Neurological difficulties commonly accompany individuals suffering from congenital disorders of glycosylation, resulting from defects in the N-glycosylation pathway. Vacant N-glycosylation sites (N220 and N229) of Kv3, voltage-gated K+ channels of high-firing neurons, deeply perturb channel activity in neuroblastoma (NB) cells. Here we examined neuron development, localization, and activity of Kv3 channels in wildtype AB zebrafish and CRISPR/Cas9 engineered NB cells, due to perturbations in N-glycosylation processing of Kv3.1b. We showed that caudal primary (CaP) motor neurons of zebrafish spinal cord transiently expressing fully glycosylated (WT) Kv3.1b have stereotypical morphology, while CaP neurons expressing partially glycosylated (N220Q) Kv3.1b showed severe maldevelopment with incomplete axonal branching and extension around the ventral musculature. Consequently, larvae expressing N220Q in CaP neurons had impaired swimming locomotor activity. We showed that replacement of complex N-glycans with oligomannose attached to Kv3.1b and at cell surface lessened Kv3.1b dispersal to outgrowths by altering the number, size, and density of Kv3.1b-containing particles in membranes of rat neuroblastoma cells. Opening and closing rates were slowed in Kv3 channels containing Kv3.1b with oligomannose, instead of complex N-glycans, which suggested a reduction in the intrinsic dynamics of the Kv3.1b α-subunit. Thus, N-glycosylation processing of Kv3.1b regulates neuronal development and excitability, thereby controlling motor activity.

Purpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first-in-human trial of a new technology, burst-wave lithotripsy (BWL). Materials and Methods: An investigational BWL and ultrasonic propulsion system was used to target a 7-mm kidney stone in the operating room before ureteroscopy (Participant A). The same system was used to target a 7.5 mm ureterovesical junction stone in clinic without anesthesia (Participant B). Results: For Participant A, a ureteroscope inserted after 9 minutes of BWL observed fragmentation of the stone to <2 mm fragments. Participant B tolerated the procedure without pain from BWL, required no anesthesia, and passed the stone on day 15. Conclusions: The first-in-human tests of BWL pulses were successful in that a renal stone was comminuted in <10 minutes, and BWL was also tolerated by an awake subject for a distal ureteral stone. Clinical Trial NCT03873259 and NCT02028559.

Background: Presence of ethanol (EtOH) may alter the relationship between blood lactate concentrations and mortality. This study compares lactate-associated mortality risk in the presence and absence of EtOH., Methods: We performed a retrospective cohort study including all patients, age >17 years, presenting from January 2012-December 2018, to an urban, academic emergency department, with a clinically measured lactate. Data were electronically abstracted from the medical record. The primary outcome was 28-day in-hospital mortality. Patients were grouped by EtOH test results as follows: 1) present (any EtOH detected), 2) absent (EtOH concentration measured and not detected), or 3) not ordered. Marginal analysis was used to calculated probability of mortality for fixed values of lactate and model covariates., Results: Of 40,956 adult emergency department patients with measured lactate, we excluded 768 (1.89%) for lactate >10.0 mmol/L, leaving 40,240 for analysis: 4,066 (10.1%) EtOH present, 10,819 (26.9%) EtOH absent, 25,355 (63%) EtOH not ordered. Of these, 1790 (4.4%) had 28-day in-hospital mortality. Marginal probability of mortality calculated for specific lactate values found less risk for EtOH Present patients versus EtOH absent patients at lactate 0.0 mmol/L (0.8% [95%CI: 0.5-1.2%] vs 3.2% [2.8-3.6%]), 2.0 mmol/L (1.5% [1.1-1.9%] vs 4.0% [3.7-4.3%]), 4.0 mmol/L (2.6% [2.2-3.1%] vs 5.0% [4.6-5.4%]), until 6.0 mmol/L (4.5% [3.7-5.4%] vs 6.2% [5.4-7.0%])., Conclusion: EtOH presence significantly alters lactate-associated mortality risk when lactate <6.0 mmol/L. Emergency department clinicians should interpret these lactate values with caution and consider other data for risk stratification when EtOH is present., Competing Interests: ARA, NJJ, BF, JH, KJ, and MKH report no conflicts of interest. DJH reports research funding from Baxter and provides research consulting to Cytoval., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Study Objective: Point-of-care ultrasonography allows rapid diagnosis in the emergency department. A previous study found that a low prevalence of emergency medicine clinicians received point-of-care ultrasonography reimbursement in 2012 (0.7%). We determine nationwide point-of-care ultrasonography reimbursement patterns for 4 subsequent years., Methods: We performed a cross-sectional study using 2012 to 2016 data from the Centers for Medicare & Medicaid Fee-for-Service Provider Utilization and Payment Data Part B, defining point-of-care ultrasonographic examinations using Current Procedural Terminology codes. The emergency medicine workforce was defined by emergency medicine, family medicine, internal medicine, critical care, and advanced practice providers who received emergency medicine-specific reimbursements. We compared patterns of point-of-care ultrasonography reimbursement among emergency physicians in 2012 versus 2016 through a 2-sample test of proportions., Results: In 2012, 342 (0.7% of total) emergency medicine workforce clinicians were reimbursed for diagnostic point-of-care ultrasonography versus 801 (1.3%) in 2016. Emergency physicians represented an increasing proportion of the total workforce, increasing from 86.0% (95% confidence interval 82.3% to 89.6%) in 2012 (N=294) to 94.6% (95% confidence interval 93.1% to 96.2%) in 2016 (N=758). From 2012 to 2016, total point-of-care ultrasonography reimbursements increased from 13,697 to 31,717, with significant growth from echocardiograms (4,127 to 14,978), abdominal examinations (3,682 to 7,140), and thoracic examinations (801 to 5,278)., Conclusion: The proportion of emergency medicine workforce clinicians receiving diagnostic point-of-care ultrasonography reimbursements, as well as the number of point-of-care ultrasonographic studies, more than doubled from 2012 to 2016. Efforts are needed to understand barriers to adoption of point-of-care ultrasonography because only a small proportion of the emergency medicine clinician workforce was reimbursed in any year., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Study Objective: The quick sequential organ failure assessment (qSOFA) was proposed to identify infected patients at risk for mortality, an indication of sepsis, in nonintensive care unit settings. This study tests whether qSOFA improves physician prediction of mortality among infected Emergency Department (ED) patients., Methods: We performed a secondary analysis of a prospective, observational study of potentially septic ED patients, conducted between two urban, academic medical centers, from July 2016 to December 2017. We enrolled ED patients with two or more systemic inflammatory response syndrome criteria and severe sepsis qualifying organ dysfunction, systolic blood pressure <90 mm Hg, or lactate ≥ 4.0 mmol/L. Infectious etiology was adjudicated retrospectively by paired physician review. We excluded noninfected patients. Treating ED physicians submitted judgment for in-hospital mortality (0%-100%) at hospital admission, and qSOFA was calculated retrospectively using ED data. The primary outcome was in-hospital mortality within 28 days. We used logistic regression to predict mortality using physician judgment, qSOFA, and combined physician judgment and qSOFA. To assess differences between models, 95% confidence intervals for area under the curve (AUC) were derived by bootstrapping with 1,000 iterations., Results: Of 405 patients meeting inclusion criteria, 195 (48.1%) were determined to have infection and analyzed. Of analyzed patients, 16 (8.2%) suffered in-hospital mortality within 28 days. Analyzed patients had a mean age of 58.3 (SD 16.5) years and 78 (40%) were female. qSOFA alone (AUC 0.63; 95% CI: 0.53-0.73) was not superior to unstructured physician judgment (AUC 0.80; 0.70-0.89) when predicting 28-day in-hospital mortality with mean AUC difference 0.17 (0.07-0.28) across bootstrapped datasets. Combining qSOFA with physician judgment (AUC 0.79; 0.69-0.89) did not improve performance compared with physician judgment alone., Conclusion: When predicting 28-day in-hospital mortality among infected ED patients, qSOFA did not outperform or improve physician judgment.

Renal colic encounters are common; in the United States alone, they represent greater than one million annual emergency department (ED) visits. Most of these stones are managed conservatively with a trial of passage. However, some lead to repeat colic episodes, secondary ED visits, increased anxiety, and increased cost. Of the 5%-10% of symptomatic stones that become lodged at the ureteropelvic junction and are larger than 5 mm, most require operative intervention. In the process of executing a NASA-funded study of ultrasonic repositioning of kidney stones, the subject was administered fluid to dilate the collecting system, placed in Trendelenburg bed positioning, and rolled to both sides. During this process a symptomatic, obstructing 9-mm ureteropelvic junction stone moved back into the kidney's lower pole/infundibulum and symptoms were immediately resolved. The patient remained asymptomatic for a period of 5 weeks at which point elective intervention was scheduled. This case demonstrates that ureteropelvic junction stones may be repositioned in a non-invasive manner, turning a stone that requires urgent intervention into one that can be managed electively.

Introduction: A considerable publication record exists comparing sensitivity and specificity of radiological ultrasound (including point of care ultrasound) to computerized tomography for stone disease. However, the practical application of in-office ultrasound to support the growing number of kidney stone centers around the world represents a nuanced topic that is ripe for study and discussion., Methods: We provide a descriptive analysis of how in-office ultrasound is being used as an adjunct to clinical care based on our experience during 50 days in clinic at an institutionally affiliated, multidisciplinary kidney stone center. Clinic subjects gave consent and underwent ultrasound as part of research studies. Ultrasonograms were shared with and verified by the treating physician before the patient was discharged from care. We counted the number of times research imaging altered the care plan., Results: Of the 60 patients enrolled the clinician used the information obtained from the studies in 20 (33%) to determine the course of clinical care that resulted in a change in treatment or process., Conclusions: Ultrasound has the potential to be a cost-effective and valuable tool that can provide more efficient workflow within a kidney stone center or urology clinic.

Background: Identifying infection is critical in early sepsis screening. This study assessed whether biomarkers of endothelial activation and/or inflammation could improve identification of infection among Emergency Department (ED) patients with organ dysfunction., Methods: We performed a prospective, observational study at two urban, academic EDs, between June 2016 and December 2017. We included admitted adults with 1) two systemic inflammatory response syndrome criteria and organ dysfunction, 2) systolic blood pressure < 90 mmHg, or 3) lactate ≥4.0 mmol/L. We excluded patients with trauma, transferred for intracranial hemorrhage, or without available blood samples. Treating ED physicians reported presence of infection (yes/no) at inpatient admission. Assays for angiopoietin-1, angiopoietin-2, soluble tumor necrosis factor receptor-1, interleukin-6, and interleukin-8 were performed using ED blood samples. The primary outcome was infection, adjudicated by paired physician review. Using logistic regression, we compared the performance of physician judgment, biomarkers, and physician judgment-biomarkers combination to predict infection. Area under the curve (AUC) and AUC 95% confidence intervals were estimated by bootstrap procedure., Results: Of 421 patients enrolled, 306 patients met final study criteria. Of these, 154(50.3%) patients had infectious etiologies. Physicians correctly discriminated infectious from non-infectious etiologies in 239 (78.1%). Physician judgment performed moderately when discriminating infection (AUC 0.78, 95% CI: 0.74-0.82) and outperformed the best biomarker model, interleukin-6 alone, (AUC 0.71, 0.66-0.76). Physician judgment improved when including interleukin-6 (AUC 0.84, 0.79-0.87), with modest AUC improvement: 0.06 (0.03-0.08)., Conclusions: In ED patients with organ dysfunction, plasma interleukin-6 may improve infection discrimination when added to physician judgment., Competing Interests: Declaration of Competing Interest DH reports providing consultation to the Washington State Hospital Association and research grant support from Baxter. NS reports his involvement in the data and safety monitoring board of Cumberland Pharmaceuticals and grant support from Cheetah Medical, Thermo-Fischer, Rapid Pathogen Screening, and Baxter. WCL is an inventor on US Patent Application No. US61/603,765 and US Patent Application No. US14/019,447, both regarding use of Ang-1 and Ang-2 as prognostic biomarkers in critical illness. No other authors have conflicts of interest to report., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Neuroblastoma (NB) development and progression are accompanied by changes in N-glycans attached to proteins. Here, we investigated the role of N-acetylglucosaminyltransferase-II (GnTII, MGAT2 ) protein substrates in neuroblastoma (NB) cells. MGAT2 was silenced in human BE(2)-C NB (HuNB) cells to generate a novel cell line, HuNB(- MGAT2 ), lacking complex type N-glycans, as in rat B35 NB cells. Changes in N-glycan types were confirmed by lectin binding assays in both cell lines, and the rescued cell line, HuNB(-/+ MGAT2 ). Western blotting of cells heterologously expressing a voltage-gated K+ channel (Kv3.1b) showed that some hybrid N-glycans of Kv3.1b could be processed to complex type in HuNB(-/+ MGAT2 ) cells. In comparing HuNB and HuNB(- MGAT2 ) cells, decreased complex N-glycans reduced anchorage-independent cell growth, cell proliferation, and cell invasiveness, while they enhanced cell-cell interactions. Cell proliferation, invasiveness and adhesion of the HuNB(-/+ MGAT2 ) cells were more like the HuNB than HuNB(- MGAT2 ). Western blotting revealed lower protein levels of MMP-2, EGFR and Gab2 in glycosylation mutant cells relative to parental cells. Gelatin zymography demonstrated that decreased MMP-2 protein activity was related to lowered MMP-2 protein levels. Thus, our results support that decreased complex type N-glycans suppress cell proliferation and cell invasiveness in both NB cell lines via remodeling ECM.

Background: Sepsis risk stratification tools typically predict mortality, although stays in the intensive care unit (ICU) of 24 hours or longer may be more clinically relevant for emergency department disposition., Objective: To explore predictors of ICU stay of 24 hours or longer among infected, hypotensive emergency department patients., Methods: A secondary analysis of 2 prospective, observational studies of adult patients with severe sepsis or an infection with a systolic blood pressure less than 90 mm Hg in 3 urban, academic emergency departments was performed. Patients with hypotension and infection were included. Patients with emergency department intubation, vasopressor administration, and/or death were excluded. The primary outcome was ICU stay of 24 hours or longer or death in less than 24 hours. Multivariable logistic regression was used to predict ICU stay of 24 hours or longer., Results: Of 233 patients, 108 (46.4%) had ICU stays of 24 hours or longer. History of heart failure (odds ratio, 3.6; 95% CI, 1.5-8.3), bicarbonate level less than 20 mEq/L (odds ratio, 2.0; 95% CI, 1.1-3.8), respiratory rate greater than 20/min (odds ratio, 2.0; 95% CI, 1.1-3.7), and creatinine level greater than 2.0 mg/dL (odds ratio, 3.6; 95% CI, 1.9-6.7) were independent predictors of ICU stay of 24 hours or longer (area under curve, 0.74). The presence of 1 of these factors predicted ICU stay of 24 hours or longer (area under curve, 0.74) with 82.4% sensitivity and 49.6% specificity., Conclusions: These exploratory results show that heart failure, bicarbonate level of less than 20 mEq/L, tachypnea, or creatinine level greater than 2.0 mg/dL increases the likelihood of an ICU stay of 24 hours or longer among infected, hypotensive emergency department patients., (©2019 American Association of Critical-Care Nurses.)

Study Objective: Observation stays are composing an increasing proportion of unscheduled hospitalizations in the United States, with unclear consequences for the quality of care. This study used a nationally representative data set of commercially insured patients hospitalized from the emergency department (ED) to compare 30-day postdischarge unplanned care events after an observation stay versus a short inpatient admission., Methods: This was a retrospective analysis of ED hospitalizations using the 2015 Truven MarketScan Commercial Claims and Encounters data set. Adult observation stays and short inpatient hospitalizations of 2 days or less were identified and followed for 30 days from hospital discharge to identify unplanned care events, defined as a subsequent inpatient admission, observation stay, or return ED visit. A propensity score analysis was used to compare rates of unplanned events after each type of index hospitalization., Results: Among the propensity-weighted cohorts, patients with an index observation stay were 28% more likely to experience any unplanned care event within 30 days of discharge compared with those with a short inpatient admission (20.4% versus 15.9%; risk ratio 1.28; 95% confidence interval [CI] 1.21 to 1.34). Specifically, patients in the observation stay group had substantially higher rates of postdischarge observation stays (4.8% versus 1.9%; odds ratio 2.60; 95% CI 2.15 to 3.16) and ED revisits with discharge (11.1% versus 8.8%; odds ratio 1.26; 95% CI 1.21 to 1.44) compared with those in the inpatient group, but were less likely to be readmitted as inpatients (6.4% versus 7.2%; odds ratio 0.90; 95% CI 0.83 to 0.96)., Conclusion: Commercially insured patients with an observation stay from the ED have a higher risk of postdischarge acute care events compared with similar patients with a short inpatient admission. Additional research is necessary to determine the extent to which quality of care, including care transitions, may differ between these 2 groups., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Study Objective: We describe the current US emergency medicine workforce in terms of clinician type and examine rural and urban emergency medicine workforce differences., Methods: Using the 2014 Medicare Public Use Files, we performed a cross-sectional study of all clinicians receiving reimbursement for evaluation and management (E/M) services (levels 1 to 5) to Medicare fee-for-service Part B beneficiaries in the emergency department. Providers were defined as emergency physicians, nonemergency physicians, or advanced practice providers, corresponding with the Medicare Public Use Files data set. The primary outcome was the number of clinicians providing greater than 10 E/M claims tabulated as a distinct encounter. Urbanicity data were obtained from the National Bureau of Economic Research., Results: Of 58,641 unique emergency medicine clinicians, 35,856 (61.1%) were classified as emergency physicians, 8,397 (14.3%) as nonemergency physicians, and 14,360 (24.5%) as advanced practice providers. Among nonemergency physicians categorized as emergency medicine clinicians, family practice and internal medicine predominated (41.7% and 19.9%, respectively). Among advanced practice providers, physician assistants (68.4%) and nurse practitioners (31.5%) predominated. A total of 58,565 emergency medicine clinicians were mapped to 2,291 US counties or equivalents. Urban counties had a higher proportion of emergency physicians (63.9%) compared with rural counties (44.8%); 27.1% of counties had no emergency medicine clinicians and 41.4% of counties had no emergency physicians reimbursed by Medicare fee-for-service Part B., Conclusion: This work establishes a new baseline estimate of the emergency care workforce, encompassing nearly 60,000 emergency medicine clinicians, of whom fewer than 2 in 3 were emergency physicians. Notable differences exist in the type of clinician staffing of emergency care between urban and rural communities., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To examine trends in the use of ED observation stays among a national sample of patients with commercial insurance, and assess the patient cost-burden of an observation stay relative to an short inpatient hospitalization from the ED., Methods: Retrospective analysis of ED observation stays and inpatient hospitalizations from 2008 to 2015 using the Truven MarketScan® Commercial Claims and Encounters database. Index ED visits were identified from claims files and assessed for evidence of an observation or inpatient hospitalization. Total and out-of-pocket costs were calculated for the index hospitalization and a 30-day episode of care and standardized to 2015 $USD. Costs for ED patients with an observation stay were compared to a similar, propensity-matched cohort of ED patients hospitalized as inpatients., Results: Over the 8 year period, observation stay admissions increased from 4.3% to 6.8% of total ED visits (60.5% relative increase) while inpatient admissions fell from 10.8% to 8.9% (16.6% relative decrease). In 2015, the mean total cost was $8162 for an observation stay and $22,865 for an inpatient hospitalization. Patient out-of-pocket costs were $962 and $1403, respectively. Among the propensity-matched cohorts, relative mean costs for the index hospitalization were 41% higher and patient out-of-pocket costs were 33% higher if the patient was admitted as an inpatient from the ED versus observation during their hospitalization., Conclusions: Observation hospitalizations are an increasingly common disposition for patients entering the hospital through the ED. Both total and patient out-of-pocket costs are lower, on average, for an observation stay compared with a similar inpatient admission for ED patients requiring hospitalization., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Modifications in surface glycans attached to proteins via N-acetylglucosamine-β1-N-asparagine linkage have been linked to tumor development and progression. These modifications include complex N-glycans with high levels of branching, fucose and sialic acid residues. Previously, we silenced Mgat2 in neuroblastoma (NB) cells, which halted the conversion of hybrid type N-glycans to complex type, to generate a novel cell line, NB&#95;1(-Mgat2). By comparing the aberrant cell properties of the NB&#95;1(-Mgat2) cell line to the parental cell line (NB&#95;1), we investigated the impact of eliminating complex type N-glycans on NB cell behavior. Further, the N-glycosylation pathway in the NB&#95;1(-Mgat2) cell line was rescued by transiently transfecting cells with Mgat2, thus creating the NB&#95;1(-/+Mgat2) cell line. Changes in the N-glycosylation pathway were verified by enhanced binding of E-PHA and L-PHA to proteins in the rescued cell line relative to those of the NB&#95;1(-Mgat2) cell line. Also, western blotting of total membranes from the rescued cell line ectopically expressing a voltage-gated K+ channel (Kv3.1b) revealed that N-glycans of Kv3.1b were processed to complex type. By employment of various cell lines, we demonstrated that reduction of the complex type N-glycans diminished anchorage-independent cell growth, and enhanced cell-cell interactions. Two independent cell invasion assays showed that cell invasiveness was markedly lessened by lowering the levels of complex type N-glycans while cell mobility was only slightly modified. Neurites of NB cells were shortened by the absence of complex type N-glycans. Cell proliferation was reduced in NB cells with lowered levels of complex type N-glycans which resulted from hindered progression through G1+Go phases of the cell cycle. Overall, our results illustrate that reducing the ratio of complex to hybrid types of N-glycans diminishes aberrant NB cell behavior and thereby has a suppressive effect in cell proliferation, and cell dissociation and invasion phases of NB., Competing Interests: The authors have declared that no competing interests exist.

Objective: Identify predictors of cardiogenic etiology among emergency department (ED) patients with hypotension, and use these predictors to create a clinical tool to discern cardiogenic etiology of hypotension., Methods: This secondary analysis evaluated a prospective cohort of consecutive patients with hypotension in an urban, academic, tertiary care ED from November 2012 to September 2013. We included adults with hypotension, defined as a new vasopressor requirement, systolic blood pressure (SBP) < 90 mm Hg after at least 1 L of crystalloid or 2 units packed red blood cells, or SBP < 90 mm Hg and fluids withheld due to concern for fluid overload. The primary outcome was cardiogenic etiology, adjudicated by two physician chart review, with 25% paired chart review (kappa = 0.92). We used multivariable logistic regression to predict cardiogenic etiology, utilizing clinical data abstracted from the electronic medical record. We created a prediction score from significant covariates and calculated its test characteristics for cardiogenic hypotension., Results: Of 700 patients with hypotension, 107 (15.3%, 95% CI: 12.6%-18.0%) had cardiogenic etiology. Independent predictors of cardiogenic etiology were shortness of breath (OR 4.1, 95% CI: 2.5-6.7), troponin > 0.1 ng/mL (37.5, 7.1-198.2), electrocardiographic ischemia (8.9, 4.0-19.8), history of heart failure (2.0, 1.1-3.3), and absence of fever (4.5, 2.3-8.7) (area under the curve [AUC] = 0.83). The prediction score created from these predictors yielded 78% sensitivity and 77% specificity for cardiogenic etiology (AUC = 0.827)., Conclusions: Clinical predictors offer reasonable ED screening sensitivity for cardiogenic hypotension, while demonstrating sufficient specificity to facilitate early cardiac interventions.

Objectives: We compared cost-effectiveness of cranial computed tomography (CT), fast sequence magnetic resonance imaging (fsMRI), and ultrasonography measurement of optic nerve sheath diameter (ONSD) for suspected acute shunt failure from the perspective of a health care organization., Methods: We modeled 4 diagnostic imaging strategies: (1) CT scan, (2) fsMRI, (3) screening ONSD by using point of care ultrasound (POCUS) first, combined with CT, and (4) screening ONSD by using POCUS first, combined with fsMRI. All patients received an initial plain radiographic shunt series (SS). Short- and long-term costs of radiation-induced cancer were assessed with a Markov model. Effectiveness was measured as quality-adjusted life-years. Utilities and inputs for clinical variables were obtained from published literature. Sensitivity analyses were performed to evaluate the effects of parameter uncertainty., Results: At a previous probability of shunt failure of 30%, a screening POCUS in patients with a normal SS was the most cost-effective. For children with abnormal SS or ONSD measurement, fsMRI was the preferred option over CT. Performing fsMRI on all patients would cost $269 770 to gain 1 additional quality-adjusted life-year compared with POCUS. An imaging pathway that involves CT alone was dominated by ONSD and fsMRI because it was more expensive and less effective., Conclusions: In children with low pretest probability of cranial shunt failure, an ultrasonographic measurement of ONSD is the preferred initial screening test. fsMRI is the more cost-effective, definitive imaging test when compared with cranial CT., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Objective: Routine CT for patients with acute flank pain has not been shown to improve patient outcomes, and it may unnecessarily expose patients to radiation and increased costs. As preliminary steps toward the development of a guideline for selective CT, we sought to determine the prevalence of clinically important outcomes in patients with acute flank pain and derive preliminary decision rules., Methods: We analyzed data from a randomized trial of CT vs. ultrasonography for patients with acute flank pain from 15 EDs between October 2011 and February 2013. Clinically important outcomes were defined as inpatient admission for ureteral stones and alternative diagnoses. Clinically important stones were defined as stones requiring urologic intervention. We sought to derive highly sensitive decision rules for both outcomes., Results: Of 2759 participants, 236 (8.6%) had a clinically important outcome and 143 (5.2%) had a clinically important stone. A CDR including anemia (hemoglobin <13.2g/dl), WBC count >11000/μl, age>42years, and the absence of CVAT had a sensitivity of 97.9% (95% CI 94.8-99.2%) and specificity of 18.7% (95% 17.2-20.2%) for clinically important outcome. A CDR including hydronephrosis, prior history of stone, and WBC count <8300/μl had a sensitivity of 98.6% (95% CI 94.5-99.7%) and specificity of 26.0% (95% 24.2-27.7%) for clinically important stone., Conclusions: We determined the prevalence of clinically important outcomes in patients with acute flank pain, and derived preliminary high sensitivity CDRs that predict them. Validation of CDRs with similar test characteristics would require prospective enrollment of 2100 patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Abnormal modifications in N-glycosylation processing are commonly associated with neurological disorders, although the impact of specific N-glycans on neuronal excitability is unknown. By replacement of complex types of N-glycans with hybrid types in neuroblastoma cells, we provide the first study that addresses how distinct N-glycan types impact neuronal excitability. Using CRISPR/Cas9 technology, NB&#95;1, a clonal cell line derived from rat neuroblastoma cells (NB), was modified to create an N-glycosylation mutant cell line, NB&#95;1 (-Mgat2), which expresses predominantly hybrid type N-glycans. Western and lectin blotting, flow cytometry, TIRF and DIC microscopy, and patch clamp studies were conducted. Lectin binding revealed the predominant type of N-glycans expressed in NB&#95;1 (-Mgat2) is hybrid while those of NB and NB&#95;1 are complex. Kv3.1 b-expressing cells with complex N-glycans localized more glycosylated Kv3.1b to the neurites than cells with hybrid N-glycans. Further the absence of N-glycan attachment to Kv3.1b was critical for sub-plasma distribution of Kv3.1b to neurites in primary adult mammalian neurons, along with NB cells. Replacement of complex type N-glycans with hybrid type hindered the opening and closing rates of outward ionic currents of Kv3.1 b-expressing NB cells. The lacks of N-glycan attachment hindered the rates even more but were not significantly different between the NB cell lines. Taken together, our evidence supports N-glycosylation impacts the sub-plasma membrane localization and activity of Kv3.1 b-containing channels. We propose that N-glycosylation processing of Kv3.1 b-containing channels contributes to neuronal excitability, and abnormal modifications in N-glycosylation processing of Kv3.1b could contribute to neurological diseases.

Objectives: The primary objectives were to describe the diagnostic characteristics tricuspid annular plane systolic excursion (TAPSE) for pulmonary embolism (PE) and to optimize the measurement cutoff of TAPSE for the diagnosis of PE. Secondary objectives included assessment of interrater reliability and the quantitative visual estimation of TAPSE., Methods: This is a prospective observational cohort study involving a convenience sample of patients at an urban academic emergency department. Patients underwent focused right heart echocardiogram (FOCUS) before computed tomographic angiography (CTA) for suspected PE., Results: A total of 150 patients were enrolled, 32 of whom (21.3%) were diagnosed as having a PE. A receiver operating characteristic curve analysis yielded 2.0 cm as the optimal cutoff for TAPSE in the diagnosis of PE, with a sensitivity of 72% (95% confidence interval [CI], 53-86), a specificity of 66% (95% CI, 57-75), and an area under the curve of 0.73 (95% CI, 0.65-0.83). In patients with tachycardia or hypotension, post hoc analysis demonstrated that FOCUS is 100% (95% CI, 80-100) sensitive for PE, whereas TAPSE is 94% (95% CI, 71-99) sensitive for PE. The intraclass correlation coefficient was 0.87 (95% CI, 0.79-0.93). Emergency physicians with training in echocardiography accurately visually estimated TAPSE, with a κ statistic of 0.94 (95% CI, 0.87-0.98)., Conclusions: Emergency physicians with training in echocardiography can reliably measure TAPSE and are able to accurately visually estimate TAPSE as either normal or abnormal. When using an abnormal cutoff of less than 2.0 cm, TAPSE has moderate diagnostic value in patients with suspected PE. On post hoc analysis, TAPSE and FOCUS appear to be highly sensitive for PE in patients with tachycardia or hypotension., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Diagnostic testing is an integral component of patient evaluation in the emergency department (ED). Emergency clinicians frequently use diagnostic testing to more confidently exclude "worst-case" diagnoses rather than to determine the most likely etiology for a presenting complaint. Increased utilization of diagnostic testing has not been associated with reductions in disease-related mortality but has led to increased overall healthcare costs and other unintended consequences (e.g., incidental findings requiring further workup, unnecessary exposure to ionizing radiation or potentially nephrotoxic contrast). Shared decision making (SDM) presents an opportunity for clinicians to discuss the benefits and harms associated with diagnostic testing with patients to more closely tailor testing to patient risk. This article introduces the challenges and opportunities associated with incorporating SDM into emergency care by summarizing the conclusions of the diagnostic testing group at the 2016 Academic Emergency Medicine Consensus Conference on SDM. Three primary domains emerged: 1) characteristics of a condition or test appropriate for SDM, 2) critical elements of and potential barriers to SDM discussions on diagnostic testing, and 3) financial aspects of SDM applied to diagnostic testing. The most critical research questions to improve engagement of patients in their acute care diagnostic decisions were determined by consensus., Competing Interests: Conflicts of Interests/Disclosures: There are no conflicts of interest in connection with this submission nor are there any copyright constraints. No industry financial support or compensation has been or will be received for conducting this study. Barrett: Consultant, Red Bull GmbH, Fuschl am See, Salzburg and Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, Connecticut; Research Support as Site Principal Investigator: Janssen Pharmaceuticals, Raritan, NJ; Alere, San Diego, CA; Others: None, (© 2016 by the Society for Academic Emergency Medicine.)

Objectives: Point-of-care ultrasound is a valuable tool with potential to expedite diagnoses and improve patient outcomes in the emergency department. However, little is known about national patterns of adoption. This study examined nationwide point-of-care ultrasound reimbursement among emergency medicine (EM) practitioners and examined regional and practitioner level variations., Methods: Data from the 2012 Center for Medicare and Medicaid Services Fee-for-Service Provider Utilization and Payment Data include all practitioners who received more than 10 Medicare Part B fee-for-service reimbursements for any Healthcare Common Procedure Coding System code in 2012. Odds ratios (ORs) and descriptive statistics were calculated to assess relationships between ultrasound reimbursement and practice location, nearby presence of an EM residency, and time elapsed since practitioner graduation., Results: Of 52,928 unique EM practitioners, 391 (0.7%) received limited ultrasound reimbursements for a total of 16,389 scans in 2012. Urban counties had an OR of 5.4 (95% confidence interval, 3.8-7.8) for receiving point-of-care ultrasound reimbursements compared to rural counties. Counties with an EM residency had an OR of 84.7 (95% confidence interval, 42.6-178.8) for reimbursement compared to counties without. The OR for receiving reimbursement was independent of medical school graduation year (P = .83); however, recent graduates performed more scans (P = .02)., Conclusions: A small minority of EM practitioners received reimbursements for point-of-care ultrasound from Medicare beneficiaries. These practitioners were more likely to reside in urban and academic settings. Future efforts should assess the degree to which our findings reflect either low point-of-care ultrasound use or low rates of billing for ultrasound examinations that are performed., (© 2016 by the American Institute of Ultrasound in Medicine.)

Glycosylation modulates growth, maintenance, and stress signaling processes. Consequently, altered N-glycosylation is associated with reduced fitness and disease. Therefore, expanding our understanding of N-glycans in altering biological processes is of utmost interest. Herein, clustered regularly interspaced short palindromic repeats/caspase9 (CRISPR/Cas9) technology was employed to engineer a glycosylation mutant Chinese Hamster Ovary (CHO) cell line, K16, which expresses predominantly hybrid type N-glycans. This newly engineered cell line enabled us to compare N-glycan effects on cellular properties of hybrid type N-glycans, to the well-established Pro(-)5 and Lec1 cell lines, which express complex and oligomannose types of N-glycans, respectively. Lectin binding studies revealed the predominant N-glycan expressed in K16 is hybrid type. Cell dissociation and migration assays demonstrated the greatest strength of cell-cell adhesion and fastest migratory rates for oligomannose N-glycans, and these properties decreased as oligomannose type were converted to hybrid type, and further decreased upon conversion to complex type. Next, we examined the roles of three general types of N-glycans on ectopic expression of E-cadherin, a cell-cell adhesion protein. Microscopy revealed more functional E-cadherin at the cell-cell border when N-glycans were oligomannose and these levels decreased as the oligomannose N-glycans were processed to hybrid and then to complex. Thus, we provide evidence that all three general types of N-glycans impact plasma membrane architecture and cellular properties.

Study Objective: Nontraumatic shock in the emergency department (ED) has multiple causes and carries in-hospital mortality approaching 20%, underscoring the need for prompt diagnosis and treatment. Diagnostic ultrasonography at the point of care is one method that may improve the ability of ED physicians to quickly diagnose and treat. This study assesses the effect of the use and timing of point-of-care (POC) ultrasonography on time to disposition request., Methods: This retrospective study across 4 Connecticut EDs compared propensity score matched shock patients who did and did not receive POC ultrasonography. Two propensity score matches were performed: the first using covariates of time to disposition from previous literature and the second using 25 novel covariates identified from electronic health records using machine learning to reduce variable selection biases., Results: A total of 3834 unique patients presented with shock during an 18-month period, and 703 (18.3%) patients received POC ultrasonography. Mean time to disposition for all patients was 255.4minutes (interquartile range, 163.8). After propensity score matching, patients had a mean reduction of 26.7minutes (95% confidence interval [CI], 2.8-58.3) in time to disposition when POC ultrasonography was performed within 1hour of ED arrival and a lesser reduction of 16.7minutes (95% CI, -2.8 to 35.5) when POC ultrasonography was performed within 2hours. There was no evidence of reduction in time to disposition when ultrasonography was performed after 2hours (16.7minutes; 95% CI, -14.3 to 29.9). Propensity score models using machine learning-selected variables yielded similar results., Conclusion: Performance of POC ultrasonography likely improves time to disposition when performed early on ED patients with shock., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Early evidence suggests that provisions of the Food and Drug Administration Safety and Innovation Act of 2012 are associated with reductions in the total number of new national drug shortages. However, drugs frequently used in acute unscheduled care such as the care delivered in emergency departments may be increasingly affected by shortages. Our estimates, based on reported national drug shortages from 2001 to 2014 collected by the University of Utah's Drug Information Service, show that although the number of new annual shortages has decreased since the act's passage, half of all drug shortages in the study period involved acute care drugs. Shortages affecting acute care drugs became increasingly frequent and prolonged compared with non-acute care drugs (median duration of 242 versus 173 days, respectively). These results suggest that the drug supply for many acutely and critically ill patients in the United States remains vulnerable despite federal efforts., (Project HOPE—The People-to-People Health Foundation, Inc.)

Background: Blunt cardiac injury severe enough to require surgical intervention (sBCI) is an exceedingly rare event occurring in approximately 1 out of every 1600 trauma patients. While performing the cardiac component of the Focused Assessment of Sonography in Trauma (cFAST) exam is effective in penetrating trauma, it is unclear whether it is of value in blunt trauma given the low prevalence of sBCI, the imperfect test characteristics of the FAST exam, and the rate of incidental pericardial effusion., Objective: The objective was to determine through decision analysis whether performing the cFAST exam is cost-effective in the evaluation of hypotensive and normotensive blunt trauma patients., Methods: We created two decision analytic models using commercially available software (TreeAgePro2011) to evaluate the cost-effectiveness of the cFAST in hypotensive (systolic blood pressure <90 mm Hg) and normotensive blunt trauma patients. Clinical probabilities were obtained from published data. Costs were estimated from Medicare reimbursement and charge data. The willingness-to-pay threshold was $50,000/quality-adjusted life-years (QALYs). Sensitivity analyses were performed over plausible ranges using available literature., Results: In hypotensive patients, for the base case scenario of a 34-year-old with blunt trauma, the cFAST strategy had a cost of $42,882.70 and an effectiveness of 25.3597 QALYs, whereas the no cFAST strategy had a cost of $42,753.52 and an effectiveness of 25.3532 QALYs. The incremental cost-effectiveness ratio (ICER) was $19,918/QALY. For normotensive patients the cFAST strategy had a cost of $18,331.03 and an effectiveness of 23.2817 QALYs, whereas the no cFAST strategy had a cost of $18,207.58 and an effectiveness of 23.2814 QALYs. The ICER was $465,867/QALY. In the sensitivity analyses, age, probability of death from sBCI with prompt treatment, and probability of sBCI were the main drivers of variability in the model outcomes., Conclusions: The cFAST for blunt trauma is cost-effective for hypotensive but not for normotensive patients. The ICER for hypotensive patients was more than 20 times higher than the ICER for normotensive patients. Our results suggest that performing the cFAST exam may not be an effective use of resources in normotensive blunt trauma patients., (© 2016 by the Society for Academic Emergency Medicine.)

Objectives: Predictive analytics in emergency care has mostly been limited to the use of clinical decision rules (CDRs) in the form of simple heuristics and scoring systems. In the development of CDRs, limitations in analytic methods and concerns with usability have generally constrained models to a preselected small set of variables judged to be clinically relevant and to rules that are easily calculated. Furthermore, CDRs frequently suffer from questions of generalizability, take years to develop, and lack the ability to be updated as new information becomes available. Newer analytic and machine learning techniques capable of harnessing the large number of variables that are already available through electronic health records (EHRs) may better predict patient outcomes and facilitate automation and deployment within clinical decision support systems. In this proof-of-concept study, a local, big data-driven, machine learning approach is compared to existing CDRs and traditional analytic methods using the prediction of sepsis in-hospital mortality as the use case., Methods: This was a retrospective study of adult ED visits admitted to the hospital meeting criteria for sepsis from October 2013 to October 2014. Sepsis was defined as meeting criteria for systemic inflammatory response syndrome with an infectious admitting diagnosis in the ED. ED visits were randomly partitioned into an 80%/20% split for training and validation. A random forest model (machine learning approach) was constructed using over 500 clinical variables from data available within the EHRs of four hospitals to predict in-hospital mortality. The machine learning prediction model was then compared to a classification and regression tree (CART) model, logistic regression model, and previously developed prediction tools on the validation data set using area under the receiver operating characteristic curve (AUC) and chi-square statistics., Results: There were 5,278 visits among 4,676 unique patients who met criteria for sepsis. Of the 4,222 patients in the training group, 210 (5.0%) died during hospitalization, and of the 1,056 patients in the validation group, 50 (4.7%) died during hospitalization. The AUCs with 95% confidence intervals (CIs) for the different models were as follows: random forest model, 0.86 (95% CI = 0.82 to 0.90); CART model, 0.69 (95% CI = 0.62 to 0.77); logistic regression model, 0.76 (95% CI = 0.69 to 0.82); CURB-65, 0.73 (95% CI = 0.67 to 0.80); MEDS, 0.71 (95% CI = 0.63 to 0.77); and mREMS, 0.72 (95% CI = 0.65 to 0.79). The random forest model AUC was statistically different from all other models (p ≤ 0.003 for all comparisons)., Conclusions: In this proof-of-concept study, a local big data-driven, machine learning approach outperformed existing CDRs as well as traditional analytic techniques for predicting in-hospital mortality of ED patients with sepsis. Future research should prospectively evaluate the effectiveness of this approach and whether it translates into improved clinical outcomes for high-risk sepsis patients. The methods developed serve as an example of a new model for predictive analytics in emergency care that can be automated, applied to other clinical outcomes of interest, and deployed in EHRs to enable locally relevant clinical predictions., (© 2015 by the Society for Academic Emergency Medicine.)

Priorities in health care delivery are shifting, with a greater focus on enhancing value, incentivizing quality, and advancing population health. While measurement of quality in emergency department (ED) care is still in its infancy, performance measures are increasingly being linked to reimbursement to encourage the delivery of high-value care. With such changes, there will be growing oversight of diagnostic imaging in all clinical settings, including the ED. Here, the authors examine the current state of quality measurement as it pertains to ED imaging. The authors review relevant policies and discuss both the associated challenges and the facilitators of using quality measures to help optimize ED imaging. Understanding such factors will help ensure the delivery of diagnostic imaging that is appropriate, high-quality, and patient-centered., (© 2015 by the Society for Academic Emergency Medicine.)