Inter-rater reliability of optic nerve sheath diameter measurement using real-time ultrasonography.

OBJECTIVES: Ultrasound measurement of the optic nerve sheath diameter (ONSD) is a rapid, non-invasive means to indirectly assess intracranial pressure. Previous research has demonstrated the ability of emergency physicians to measure ONSD accurately with bedside ultrasound when compared to CT scan or MRI, however the reliability of this measurement between two or more operators has been called into question (Hassen et al. in J Emerg Med 48:450-457, 2015; Shirodkar et al. in Ind J Crit Care Med 19:466-470, 2015). Given the need for accurate and precise measurement to use this as a screening exam, we sought to determine the inter-rater reliability between ONSD measurements obtained in real time by fellowship-trained emergency ultrasound physicians. METHODS: Three ultrasound fellowship-trained emergency physicians measured bilateral ONSD of 10 healthy volunteers using a high-frequency linear transducer. The physicians were blinded to the other scanners' measurements, and no instructions were given other than to obtain the ONSD. Each sonographer measured the ONSD in real time and it was recorded by a research coordinator. All measurements were recorded in millimeters. Intraclass correlation coefficients (ICCs) were calculated to estimate the inter-rater reliability. RESULTS: A total of 60 measurements of ONSD were obtained. The average measurement was 4.3 mm (3.83-4.77). Very little variation was found between the three physicians, with a calculated ICC of 0.82 (95% confidence interval 0.63-0.92). CONCLUSIONS: ONSD measurement obtained by ultrasound fellowship-trained emergency medicine physicians is a reliable measurement with a high degree of correlation between scanners.

Novel Approach to Ultrasound-Guided Thoracostomy.

OBJECTIVES: Thoracostomy is often a required treatment in patients with thoracic trauma; however, performing a thoracostomy using traditional techniques can have complications. Ultrasound can be a beneficial tool for identifying the correct thoracostomy insertion site. We designed a randomized prospective study to assess if ultrasound guidance can improve thoracostomy site identification over traditional techniques. METHODS: Emergency medicine residents were randomly assigned to use palpation or ultrasound to identify a safe insertion site for thoracostomy placement. The target population comprised of hemodynamically stable trauma patients who received an extended focused assessment with sonography for trauma (EFAST) and a chest computed tomography (CT) exam. The resident placed a radiopaque marker on the skin of the patient where a safe intercostal space was believed to be located, either by palpation or ultrasound. Clinical ultrasound faculty reviewed the CT to confirm marker placement relative to the diaphragm. A Fischer's exact test was used to analyze the groups. RESULTS: One hundred and forty-seven patients were enrolled in the study, 75 in the ultrasound group and 72 in the landmark group. This resulted in the placement of 271 total thoracostomy site markers, 142 by ultrasound and 129 by palpation and landmarks. The ultrasound group correctly identified thoracostomy insertion sites above the diaphragm in 97.2% (138/142) of patients, while the palpation group identified a safe insertion site in 88.4% (114/129) of patients (P = .0073). CONCLUSION: This study found that emergency medicine residents are more likely to identify a safe tube thoracostomy insertion site in trauma patients by using ultrasound, as compared to using landmarks and palpation.

A retrospective evaluation of point of care ultrasound for acute cholecystitis in a tertiary academic hospital setting.

BACKGROUND: In 2008 the Council of Emergency Medicine Residency Directors delineated consensus recommendations for training in biliary ultrasound for the "detection of biliary pathology". OBJECTIVES: While studies have looked at the accuracy of emergency provider performed clinical ultrasound (ECUS), we sought to evaluated if ECUS could be diagnostic for acute cholecystitis and thus obviate the need for follow-up imaging. METHOD: We reviewed all ECUS performed between 2012 and 2017 that had a matching radiology performed ultrasound (RADUS) and a discharge diagnosis. 332 studies were identified. The sensitivity and specificity of both ECUS and RADUS were compared to the patient's discharge diagnosis. The agreement between the ECUS and RADUS was assessed using an unweighted Cohen's Kappa. The time from patient arrival to diagnosis by ECUS and RADUS was also compared. RESULTS: Using discharge diagnosis as the gold standard ECUS was 67% (56-78%) sensitive, 88% (84-92%) specific, NPV 90% (87-95%), PPV 60% (50-71%), +LR 5.6 (3.9-8.2), -LR 0.37 (0.27-0.52) for acute cholecystitis. RADUS was 76% (66-87%) sensitive, 97% (95-99%) specific, NPV 95% (092-97%), PPV 86% (76-95%), +LR 25.6 (12.8-51.4), and -LR 0.24 (0.15-0.38). ECUS was able to detect gallstones with 93% (89-96%) sensitivity and 94% (90-98%) specificity leading to a NPV 90% (85-95%), PPV of 95% (92-98%), +LR 14.5 (7.7-27.4), -LR 0.08 (0.05-0.13). The unweighted kappa between ECUS and RADUS was 0.57. The median time between obtaining ECUS vs. RADUS diagnosis was 124 min. CONCLUSIONS: ECUS can be beneficial in ruling out acute cholecystitis, but lacks the test characteristics to be diagnostic for acute cholecystitis.

Central Venous Catheter Confirmation by Ultrasonography: A Novel Instructional Protocol.

OBJECTIVES: Ultrasound (US)-only confirmation of central venous catheter (CVC) placement has proven to be accurate and fast when compared with the current standard chest radiograph. This procedure depends on the detection of appropriately timed atrial bubbles during central line flushing, called the rapid atrial swirl sign (RASS). The most obvious barrier to increasing the use of this technique is appropriate education and training; therefore, we proposed a novel educational approach to training emergency department (ED) physicians in the confirmation of CVC location using US and then tested its effectiveness. METHODS: Using an online educational model, participants were taught the background and procedural steps to confirm CVC placement using US. Subsequently, they were asked to use this knowledge to place central lines in simulation and confirm them using US. They were tested with various scenarios, including correctly and incorrectly placed lines. Their accuracy was measured, and a survey was used to assess their satisfaction with the training and applicability to practice. RESULTS: A total of 47 ED physicians completed the online training module and 24 completed the simulation testing that followed. Results showed 100% accuracy in detecting appropriately timed RASS (<2 seconds), delayed RASS (>2 seconds), and no RASS in simulation. All of the participants "agreed" or "strongly agreed" that the didactic and simulation sessions improved their understanding of US confirmation of central line placement. CONCLUSIONS: The use of US to confirm central line placement can be effectively taught to ED physicians using short didactic and simulation-based training. This is a reasonable approach to integrate this protocol into practice, and allow for more widespread use of this emerging technique.

Patient Safety Event Reporting and Opportunities for Emergency Medicine Resident Education.

INTRODUCTION: Healthcare systems often expose patients to significant, preventable harm causing an estimated 44,000 to 98,000 deaths or more annually. This has propelled patient safety to the forefront, with reporting systems allowing for the review of local events to determine their root causes. As residents engage in a substantial amount of patient care in academic emergency departments, it is critical to use these safety event reports for resident-focused interventions and educational initiatives. This study analyzes reports from the Virginia Commonwealth University Health System to understand how the reports are categorized and how it relates to opportunities for resident education. METHODS: Identifying categories from the literature, three subject matter experts (attending physician, nursing director, registered nurse) categorized an initial 20 reports to resolve category gaps and then 100 reports to determine inter-rater reliability. Given sufficient agreement, the remaining 400 reports were coded individually for type of event and education among other categories. RESULTS: After reviewing 513 events, we found that the most common event types were issues related to staff and resident training (25%) and communication (18%), with 31% requiring no education, 46% requiring directed educational feedback to an individual or group, 20% requiring education through monthly safety updates or meetings, 3% requiring urgent communication by email or in-person, and <1% requiring simulation. CONCLUSION: Twenty years after the publication of To Err is Human, gains have been made integrating quality assurance and patient safety within medical education and hospital systems, but there remains extensive work to be done. Through a review and analysis of our patient safety event reporting system, we were able to gain a better understanding of the events that are submitted, including the types of events and their severity, and how these relate to the types of educational interventions provided (eg, feedback, simulation). We also determined that these events can help inform resident education and learning using various types of education. Additionally, incorporating residents in the review process, such as through root cause analyses, can provide residents with high-quality, engaging learning opportunities and useful, lifelong skills, which is invaluable to our learners and future physicians.

Detecting direct oral anticoagulants in trauma patients using liquid chromatography-mass spectrometry: A novel approach to medication reconciliation.

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSION: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. LEVEL OF EVIDENCE: Diagnostic Test, level III.

Medications and patient safety in the trauma setting: a systematic review.

Background: Medication errors account for the most common adverse events and a significant cause of mortality in the USA. The Joint Commission has required medication reconciliation since 2006. We aimed to survey the literature and determine the challenges and effectiveness of medication reconciliation in the trauma patient population. Materials and methods: We conducted a systematic review of the literature to determine the effectiveness of medication reconciliation in trauma patients. English language articles were retrieved from PubMed/Medline, CINAHL, and Cochrane Review databases with search terms "trauma OR injury, AND medication reconciliation OR med rec OR med rek, AND effectiveness OR errors OR intervention OR improvements." Results: The search resulted in 82 articles. After screening for relevance and duplicates, the 43 remaining were further reviewed, and only four articles, which presented results on medication reconciliation in 3041 trauma patients, were included. Two were retrospective and two were prospective. Two showed only 4% accuracy at time of admission with 48% of medication reconciliations having at least one medication discrepancy. There were major differences across the studies prohibiting comparative statistical analysis. Conclusions: Trauma medication reconciliation is important because of the potential for adverse outcomes given the emergent nature of the illness. The few articles published at this time on medication reconciliation in trauma suggest poor accuracy. Numerous strategies have been implemented in general medicine to improve its accuracy, but these have not yet been studied in trauma. This topic is an important but unrecognized area of research in this field.

Comparison of Ultrasound-Guided and Landmark-Based Lumbar Punctures in Inexperienced Resident Physicians.

OBJECTIVES: We sought to determine whether US-guided lumbar puncture reduced the rate of lumbar puncture failures for providers at an academic teaching hospital with variable lumbar puncture and US experience compared to the traditional landmark-based technique. METHODS: We conducted a prospective randomized controlled trial to compare US-guided lumbar puncture to the traditional landmark technique in an academic emergency department. Thirty-five patients were randomized to either have their lumbar puncture performed either via the landmark or US-guided technique. All procedures were completed by an emergency medicine resident with variable lumbar puncture and US experience. Procedural failures, the number of attempts, the time to completion, and patient pain scores were all recorded. RESULTS: The adjusted odds ratio of successfully obtaining cerebrospinal fluid (CSF) in the US-guided lumbar puncture group was 2.31 compared to the landmark-based lumbar puncture group (P = .377). It took 1.54 times more attempts to obtain CSF in the landmark group as it did in the US group (P = .046). It seemed to have no effect on postprocedural pain or the time to obtain CSF. CONCLUSIONS: The use of US guidance to assist in lumbar punctures did not improve the procedural success rate over traditional landmark techniques in an academic setting with novice providers. Although using US for procedural guidance significantly decreased the number of attempts, it seemed to have no effect on postprocedural pain or the time to obtain CSF.

Ultrasound-guided thoracostomy site identification in healthy volunteers.

BACKGROUND: Traditional landmark thoracostomy technique has a known complication rate up to 30%. The goal of this study is to determine whether novice providers could more accurately identify the appropriate intercostal site for thoracostomy by ultrasound guidance. METHODS: 33 emergency medicine residents and medical students volunteered to participate in this study during routine thoracostomy tube education. A healthy volunteer was used as the standardized patient for this study. An experienced physician sonographer used ultrasound to locate a site at mid-axillary line between ribs 4 and 5 and marked the site with invisible ink that can only be revealed with a commercially available UV LED light. Participants were asked to identify the thoracostomy site by placing an opaque marker where they would make their incision. The distance from the correct insertion site was measured in rib spaces. The participants were then given a brief hands-on training session using ultrasound to identify the diaphragm and count rib spaces. The participants were then asked to use ultrasound to identify the proper thoracostomy site and mark it with an opaque marker. The distance from the proper insertion site was measured and recorded in rib spaces. RESULTS: The participants correctly identified the pre-determined intercostal space using palpation 48% (16/33) of the time, versus the ultrasound group who identified the proper intercostal space 91% (30/33) of the time. On average, the traditional technique was placed 0.88 rib spaces away (95 CI 0.43-1.03), while the ultrasound-guided technique was placed 0.09 rib spaces away (95 CI 0.0-0.19) [P = 0.003]. CONCLUSIONS: The ability to accurately locate the correct intercostal space for thoracostomy incision was improved under ultrasound guidance. Further studies are warranted to determine if this ultrasound-guided technique will decrease complications with chest tube insertion and improve patient outcomes.

Non-invasive characterization of hemodynamics in adult out-of-hospital cardiac arrest patients soon after return of spontaneous circulation.

BACKGROUND: Little is known about hemodynamics in adult, out-of-hospital (OHCA) patients following return of spontaneous circulation (ROSC). A 1994 study when "high-dose epinephrine" use was common showed consistently elevated systemic vascular resistance (SVR) lasting ≥6 h in 49 adult patients after return of spontaneous circulation (ROSC). STUDY AIM: To characterize hemodynamic abnormalities in adult OHCA patients soon after ROSC. Our hypothesis was that, unlike the consistently high SVR values reported when "high-dose" epinephrine was in common use, there would be a more heterogenous distribution of SVR values using current adrenergic therapy. METHODS: We included adult, OHCA patients transported by paramedics to the Emergency Department (ED) post-ROSC. Children, prisoners, pregnant women, and those with ongoing CPR or arrest due to traumatic injury were excluded. Hemodynamics were recorded non-invasively as soon as feasible after ED arrival but were not used to influence therapy, which was guided by clinical judgment of treating ED physicians. RESULTS: Hemodynamics were recorded on 30 patients 20 [16,25] minutes after ED arrival: 50% had a normal SVR, 30% had a high SVR, and 20% had a low SVR. There was no difference in survival to admission among groups, although there was a difference among groups in survival to discharge. Comparing the low SVR group vs the combined normal and high group revealed a trend for fewer 0/6 (0%) low vs. 10/24 (42%) normal or high SVR patients surviving to hospital discharge (p = .053). CONCLUSION: A heterogeneous range of hemodynamic states exist post-ROSC rather than consistent vasoconstriction. Adequately powered, randomized clinical trials will be needed to determine whether noninvasively-derived, hemodynamic-directed therapy can play a role in improving neurologically-intact survival following OHCA in adults.

Emergency Physician-performed Transesophageal Echocardiography in Simulated Cardiac Arrest.

INTRODUCTION: Transesophageal echocardiography (TEE) is a well-established method of evaluating cardiac pathology. It has many advantages over transthoracic echocardiography (TTE), including the ability to image the heart during active cardiopulmonary resuscitation. This prospective simulation study aims to evaluate the ability of emergency medicine (EM) residents to learn TEE image acquisition techniques and demonstrate those techniques to identify common pathologic causes of cardiac arrest. METHODS: This was a prospective educational cohort study with 40 EM residents from two participating academic medical centers who underwent an educational model and testing protocol. All participants were tested across six cases, including two normals, pericardial tamponade, acute myocardial infarction (MI), ventricular fibrillation (VF), and asystole presented in random order. Primary endpoints were correct identification of the cardiac pathology, if any, and time to sonographic diagnosis. Calculated endpoints included sensitivity, specificity, and positive and negative predictive values for emergency physician (EP)-performed TEE. We calculated a kappa statistic to determine the degree of inter-rater reliability. RESULTS: Forty EM residents completed both the educational module and testing protocol. This resulted in a total of 80 normal TEE studies and 160 pathologic TEE studies. Our calculations for the ability to diagnose life-threatening cardiac pathology by EPs in a high-fidelity TEE simulation resulted in a sensitivity of 98%, specificity of 99%, positive likelihood ratio of 78.0, and negative likelihood ratio of 0.025. The average time to diagnose each objective structured clinical examination case was as follows: normal A in 35 seconds, normal B in 31 seconds, asystole in 13 seconds, tamponade in 14 seconds, acute MI in 22 seconds, and VF in 12 seconds. Inter-rater reliability between participants was extremely high, resulting in a kappa coefficient across all cases of 0.95. CONCLUSION: EM residents can rapidly perform TEE studies in a simulated cardiac arrest environment with a high degree of precision and accuracy. Performance of TEE studies on human patients in cardiac arrest is the next logical step to determine if our simulation data hold true in clinical practice.

Perceived Difficulty and Success Rate of Standard Versus Ultrasound-Guided Peripheral Intravenous Cannulation in a Novice Study Group: A Randomized Crossover Trial.

OBJECTIVES: To our knowledge, no previous studies have evaluated the perceived levels of difficulty between traditional and ultrasound (US)-guided peripheral intravenous (IV) access in the novice provider. We attempt to show that, in a group of medical students who have limited peripheral IV experience, US-guided peripheral IV cannulation can be achieved more effectively and with a lesser degree of difficulty than standard peripheral IV cannulation. METHODS: We performed a randomized crossover study of 61 first- and second-year medical students. After a 1-hour training session, participants were randomized to either standard cannulation on a standard peripheral IV trainer or US-guided cannulation on a standard US IV trainer. RESULTS: One hundred percent (61 of 61) of the participants in the US-guided IV group successfully achieved cannulation versus 56% (34 of 61) of the participants in the standard IV group (P < .001). The average number of attempts to obtain access in the US-guided IV group was 1.31 versus 2.16 in the standard IV group (P < .001). The average difficulty score assigned to US-guided cannulation was 2.81 of 10 versus 3.90 of 10 in the standard IV group (P = .003). CONCLUSIONS: Our study shows a decrease in perceived difficulty and a concomitant increased ability to cannulate a vein using US versus traditional landmark guidance techniques, even in the novice phlebotomist.

Alpha-lipoic acid potently inhibits peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation: implications for the neuroprotective effects of alpha-lipoic acid.

Alpha-lipoic acid (LA) has recently been reported to afford protection against neurodegenerative disorders in humans and experimental animals. However, the mechanisms underlying LA-mediated neuroprotection remain an enigma. Because peroxynitrite has been extensively implicated in the pathogenesis of various forms of neurodegenerative disorders, this study was undertaken to investigate the effects of LA in peroxynitrite-induced DNA strand breaks, a critical event leading to peroxynitrite-elicited cytotoxicity. Incubation of phi X-174 plasmid DNA with the 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, led to the formation of both single- and double-stranded DNA breaks in a concentration- and time-dependent fashion. The presence of LA at 100-1,600 microM was found to significantly inhibit SIN-1-induced DNA strand breaks in a concentration-dependent manner. The consumption of oxygen induced by 250 microM SIN-1 was found to be decreased in the presence of high concentrations of LA (400-1,600 microM), indicating that LA at these concentrations may affect the generation of peroxynitrite from auto-oxidation of SIN-1. It is observed that incubation of the plasmid DNA with authentic peroxynitrite resulted in a significant formation of DNA strand breaks, which could also be dramatically inhibited by the presence of LA (100-1,600 microM). EPR spectroscopy in combination with spin-trapping experiments, using 5,5-dimethylpyrroline-N-oxide (DMPO) as spin trap, resulted in the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from authentic peroxynitrite and LA at 50-1,600 microM inhibited the adduct signal. Taken together, these studies demonstrate for the first time that LA can potently inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. In view of the critical involvement of peroxynitrite in the pathogenesis of various neurodegenerative diseases, the inhibition of peroxynitrite-mediated DNA damage by LA may be responsible, at least partially, for its neuroprotective activities.

Simian virus 40 small t antigen mediates conformation-dependent transfer of protein phosphatase 2A onto the androgen receptor.

The tumor antigens simian virus 40 small t antigen (ST) and polyomavirus small and medium T antigens mediate cell transformation in part by binding to the structural A subunit of protein phosphatase 2A (PP2A). The replacement of B subunits by tumor antigens inhibits PP2A activity and prolongs phosphorylation-dependent signaling. Here we show that ST mediates PP2A A/C heterodimer transfer onto the ligand-activated androgen receptor (AR). Transfer by ST is strictly dependent on the agonist-activated conformation of AR, occurs within minutes of the addition of androgen to cells, and can occur in either the cytoplasm or the nucleus. The binding of ST changes the conformation of the A subunit, and ST rapidly dissociates from the complex upon PP2A A/C heterodimer binding to AR. PP2A is transferred onto the carboxyl-terminal half of AR, and the phosphatase activity is directed to five phosphoserines in the amino-terminal activation function region 1, with a corresponding reduction in transactivation. Thus, ST functions as a transfer factor to specify PP2A targeting in the cell and modulates the transcriptional activity of AR.

Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci alters phosphorylation and coactivator interactions.

Here we report that mutations within the DNA-binding domain of AR, shown previously to inhibit nuclear export to the cytoplasm, cause an androgen-dependent defect in intranuclear trafficking of AR. Mutation of two conserved phenylalanines within the DNA recognition helix (F582, 583A) results in androgen-dependent arrest of AR in multiple subnuclear foci. A point mutation in one of the conserved phenylalanines (DeltaF582, F582Y) is known to cause androgen insensitivity syndrome (AIS). Both AIS mutants (DeltaF582, F582Y) and the export mutant (F582, 583A) displayed androgen-dependent arrest in foci, and all three mutants promoted androgen-dependent accumulation of the histone acetyl transferase CREB binding protein (CBP) in the foci. The foci correspond to a subnuclear compartment that is highly enriched for the steroid receptor coactivator glucocorticoid receptor-interacting protein (GRIP)-1. Agonist-bound wild-type AR induces the redistribution of GRIP-1 from foci to the nucleoplasm. This likely reflects a direct interaction between these proteins because mutation of a conserved residue within the major coactivator binding site on AR (K720A) inhibits AR-dependent dissociation of GRIP-1 from foci. GRIP-1 also remains foci-associated in the presence of agonist-bound F582, 583A, DeltaF582, or F582Y forms of AR. Two-dimensional phospho-peptide mapping and analysis with a phospho-specific antibody revealed that mutant forms of AR that arrest in the subnuclear foci are hypophosphorylated at Ser81, a site that normally undergoes androgen-dependent phosphorylation. Our working model is that the subnuclear foci are sites where AR undergoes ligand-dependent engagement with GRIP-1 and CBP, a recruitment step that occurs before Ser81 phosphorylation and association with promoters of target genes.