Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

Risk Factors Associated With SARS-CoV-2 Seropositivity Among US Health Care Personnel.

Importance: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. Objective: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. Design, Setting, and Participants: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. Exposures: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. Main Outcome and Measures: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. Results: Among 24 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). Conclusions and Relevance: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.

Is E-Learning Education Effective in Increasing the Ability of Nonphysician Medical Flight Crewmembers to Accurately Interpret Point-of-Care Lung and Cardiac Ultrasound Examinations?

OBJECTIVE: Patients suffering from severe injury or illness can benefit from the care and transport of helicopter emergency medical services (HEMS). This may be due to the speed of transport, level of care, expertise of flight crews, and access to specialized equipment and tools. One such tool is point-of-care ultrasound (POCUS). POCUS-based lung and cardiac evaluations can positively influence the assessment and care provided to critically ill HEMS patients, but how these procedures can best be learned by nonphysician flight crewmembers has not been fully explored. METHODS: In this prospective, interventional study, 26 flight crewmembers were evaluated before and after a succinct, guided educational intervention focused on the use of free open-access medical education material intended to help them acquire the knowledge needed to accurately identify and interpret POCUS assessments. RESULTS: After completing the educational intervention, participants had a statistically significant improvement in their postintervention scores. CONCLUSION: This study supports the use of free open-access medical education material in improving the knowledge needed for nonphysician flight crewmembers to interpret basic lung and cardiac ultrasound images. Integrating this information into educational programs may contribute to increased comfort and proficiency and serve to accelerate the adoption of this tool in the air medical environment.

Validation of COVID-19 serologic tests and large scale screening of asymptomatic healthcare workers.

OBJECTIVES: Serologic testing for SARS-CoV-2 is an important element in the fight to slow the COVID-19 pandemic. This study aimed to validate two serologic tests for total (IgM, IgG, IgA) SARS-CoV-2 antibodies, (i) the Ortho-Clinical Diagnostics Anti-SARS-CoV-2 Total Antibody assay for the Vitros 5600 analyzers and (ii) a manual laboratory developed ELISA (FDA EUA pending), for use in parallel orthogonal testing of asymptomatic healthcare workers and affiliates of the University of Maryland Medical System. DESIGN AND METHODS: Validation and verification of the two tests was performed using samples from hospitalized patients that were found to be PCR positive for SARS-CoV-2, samples pre-COVID-19, and samples from individuals with current/previous infections with other viruses. Healthcare workers and affiliates from across the University of Maryland Health System were provided testing free of charge and their results were reported as reactive or non-reactive if the two tests were concordance, or indeterminate if the results were discordant. RESULTS: Validation testing found the Ortho Vitros test to be 100% (73/73) sensitive, and 99.3% (152/153) specific, while the UMMC ELISA was found to be 97.6% (204/209) sensitive and 100% (288/288) specific. Real world testing among 8399 healthcare workers found that 2.9% (247/8399) of healthcare workers were positive for anti- SARS-CoV-2 antibodies by both tests. An indeterminate rate of 1.1% (91/8399), in which one test reported reactive results, and one as non-reactive was also seen. CONCLUSIONS: Parallel orthogonal testing improves the positive and negative predictive value of serologic testing in populations with low prevalence. The use of an indeterminate result from parallel orthogonal testing allows for the follow-up and re-testing, which helps resolve discrepancies between assays.

Cheiro-Oral syndrome.

The Cheiro-Oral (COS) Syndrome is a rare neurologic condition characterized by sensory disturbances involving the peri-oral area and the upper extremity, typically isolated to the hand or fingers. The thalamus contralateral to the symptomatic side is the brain region most commonly involved. Most cases are caused by ischemic or hemorrhagic strokes, although other structural lesions have been implicated. These include tumors, subdural hematomas, aneurysms, and infections. The unusual and seemingly unrelated nature of the symptoms may contribute to misdiagnosis and incomplete workup for potentially serious conditions. We are unable to identify a report of this condition in the emergency medicine literature despite the emergency department being the likely point of presentation for patients with COS. In this report, we describe two patients with COS who presented to our emergency department and review the features of COS as described in published case reports.

Decreasing Patient Dwell Times for Outpatient Cardiac Nuclear Medicine Studies: The Benefits of SMART Goals, Scope Limitations, and Society Guidelines in Quality Improvement.

BACKGROUND: We describe a quality improvement project to improve patient dwell times for outpatient cardiac nuclear medicine exams. Preliminary data indicated that the mean patient dwell time was about 270 minutes. Our specific, measurable, achievable, relevant, and time-bound goal was to reduce patient dwell times for outpatient pharmacologically stressed cardiac nuclear medicine exams by 60 minutes over the course of 2 months. METHODS: An interdisciplinary team was formed which used staff interviews and workflow observation to create a cause and effect diagram as well as a process map. Review of the national guidelines for cardiac nuclear medicine exams identified rest and stress intervals as intervention targets. A new protocol was designed and implemented. RESULTS: The mean patient dwell time was improved from 270 to 184 minutes. CONCLUSIONS: Overall, we found that a clear specific, measurable, achievable, relevant, and time-bound goal, limited scope, and national guideline review allowed for a successful quality improvement project.

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters in Predicting Prognosis for Patients With Cervical Cancer.

OBJECTIVE. The purpose of this study is to evaluate the prognostic value of quantitative metabolic parameters from pretreatment PET/CT scans of patients with squamous cell cervical cancer. MATERIALS AND METHODS. This retrospective study included 120 patients with biopsy-proven squamous cell carcinoma of the cervix who underwent FDG PET/CT for initial tumor staging. The primary tumor maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), tumor glycolytic activity, metabolic tumor volume (MTV), and metabolic intratumoral heterogeneity index (calculated as the AUC for the cumulative standardized uptake value [SUV]-volume histogram [CSH] index) were obtained. Information on patient demographic characteristics and tumor staging were collected. Median follow-up was 27.5 months. Overall survival (OS) and progression-free survival (PFS) were calculated using a multivariate Cox proportional hazards regression model and log-rank (Mantel-Cox) test to generate Kaplan-Meier survival plots. RESULTS. The mean (± SD) age of the patients was 54.4 ± 13.1 years. Twenty-two patients had stage I disease; 58, stage II; 23, stage III; and 17, stage IV. Thirty-three patients died, 82 were living, and five were lost to follow-up and were censored; 29 patients had disease progression. The median survival was 74.9 months (95% CI, 63.6-86.9 months). A higher MTV was significantly associated with reduced OS in multivariate analysis (hazard ratio, 1.085; 95% CI, 1.036-1.136; p = 0.0005). A higher AUC-CSH index (denoting lower tumor heterogeneity) was significantly associated with increased OS (hazard ratio, 0.662; 95% CI, 0.448-0.979; p = 0.04) and PFS (hazard ratio, 0.683; 95% CI, 0.471-0.991; p = 0.045) in multivariate analysis. Kaplan-Meier survival analysis using the median value for MTV (61 mL) significantly predicted OS (p = 0.0009). CONCLUSION. Tumor heterogeneity on pretreatment PET/CT is associated with OS and PFS in patients with cervical cancer. MTV is significantly associated with OS.

Dashboard visualizations: Supporting real-time throughput decision-making.

Providing timely and effective care in the emergency department (ED) requires the management of individual patients as well as the flow and demands of the entire department. Strategic changes to work processes, such as adding a flow coordination nurse or a physician in triage, have demonstrated improvements in throughput times. However, such global strategic changes do not address the real-time, often opportunistic workflow decisions of individual clinicians in the ED. We believe that real-time representation of the status of the entire emergency department and each patient within it through information visualizations will better support clinical decision-making in-the-moment and provide for rapid intervention to improve ED flow. This notion is based on previous work where we found that clinicians' workflow decisions were often based on an in-the-moment local perspective, rather than a global perspective. Here, we discuss the challenges of designing and implementing visualizations for ED through a discussion of the development of our prototype Throughput Dashboard and the potential it holds for supporting real-time decision-making.

Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma.

BACKGROUND: Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery. METHODS: All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+). RESULTS: Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival. CONCLUSIONS: Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease.

Prognostic utility of plasma lactate measured between 24 and 48 h after initiation of early goal-directed therapy in the management of sepsis, severe sepsis, and septic shock.

BACKGROUND: Based on the proven efficacy of lactate in predicting mortality and morbidity in sepsis when measured early in the resuscitative protocol, our group hypothesized that this utility extends later in the course of care. This study sought to investigate the prognostic potential of plasma lactate clearance measured 24-48 h after the initiation of treatment for nonsurgical patients with sepsis, severe sepsis, and septic shock. METHODS: Plasma lactate values, measured 24-48 h after the initiation of treatment, were collected in nonsurgical septic, severe septic, and septic shock patients. The primary outcome was 30-day mortality, while secondary outcomes included requirements for vasopressors and boluses of intravenous fluids. Analysis of these three outcomes was performed while controlling for clinical severity as measured by Sequential Organ Failure Assessment (SOFA), renal dysfunction, and hepatic dysfunction. Lactate clearance was defined as the percent change in plasma lactate levels measured after 24-48 h of treatment from the plasma lactate level at initial presentation. RESULTS: Two hundred twenty-nine nonsurgical patients were divided into two groups, clearers (above median lactate clearance [31.6 %]) and nonclearers (below median lactate clearance [31.6 %]). The adjusted odds ratio of mortality in clearers compared to nonclearers was 0.39 (CI 0.20-0.76) (p = 0.006). For vasopressor requirement, the adjusted odds ratio was 0.41 (CI 0.21-0.79) in clearers compared to nonclearers (p = 0.008). For intravenous fluid bolus requirement, the adjusted odds ratio was 0.81 (CI 0.48-1.39) in clearers compared to nonclearers (p = 0.45). CONCLUSIONS: Lower plasma lactate clearance 24-48 h after the initiation of treatment is associated with higher 30-day mortality and requirements for vasopressors in nonsurgical septic patients and may be a useful noninvasive measurement for guiding late-sepsis treatment. Further investigation looking at mechanisms and therapeutic targets to improve lactate clearance in late sepsis may improve patient mortality and outcomes.

Clinical and angiographic outcomes after stent-assisted coiling of cerebral aneurysms with Enterprise and Neuroform stents: a comparative analysis of the literature.

INTRODUCTION: The most widely used intracranial stents for stent-assisted coiling are Neuroform (NEU) and Enterprise stents (ENT). This study compares published outcomes between the ENT and NEU coil-assist systems and comments on the published safety and efficacy of stent-assisted coiling in general. METHODS: A literature search was performed through PubMed for all published series of ENT or NEU stent-assisted coiling of cerebral aneurysms from 2004 to 2014. All studies including 10 or more published cases of stent-assisted coiling with ENT or NEU were included. RESULTS: 47 studies met the inclusion criteria, containing 4238 aneurysms in 4039 patients. 2111 aneurysms were treated with NEU and 2127 were treated with ENT. Mean follow-up was 14.1 months. Overall, thromboembolic events occurred in 6.4% of aneurysms, intracranial hemorrhage (ICH) in 2.6%, permanent morbidity in 3.9%, and mortality in 2.3%. Initial and final 100% angiographic occlusion was seen in 53% and 69% of patients, respectively. Deployment failures (p<0.001), ICH (p=0.001), mortality among all patients (p=0.03), and recanalization (p=0.02) were more commonly reported in NEU treated aneurysms. The ENT system was also associated with higher reported complete occlusion at follow-up (p<0.001). CONCLUSIONS: This literature review represents the largest and most robust comparison of stent-assisted coiling devices to date, containing over 4200 aneurysms in more than 4000 patients. Comparative analyses demonstrate that both devices are reported to be safe and effective with comparable permanent morbidity.

A comparison of two techniques for tungsten carbide ring removal.

INTRODUCTION: Emergency physicians may have difficulty removing modern rings made of hard metals such as titanium and tungsten carbide. These metals are exceptionally difficult or impossible to remove using standard ring cutters. Numerous alternative techniques for removal have been described, including the "umbilical tape" or "string technique" and, in the case of tungsten carbide, breaking the ring using locking pliers. OBJECTIVE: We sought to compare the speed and effectiveness of tungsten carbide ring removal using these two techniques. METHODS: Ten tungsten carbide rings were placed upon the finger of a standard medical simulation mannequin. The rings chosen were one-half size smaller than the mannequin's finger. Edema distal to the ring was simulated using foam tape. A single novice operator performed 10 trials using each of the techniques after a 10-minute orientation session. The success or failure of the technique and the time for removal were recorded for each trial. The mean removal times for the trials were compared using a paired t test. RESULTS: All trials were successful. The rings were removed substantially faster using the locking pliers method (mean 23.1 seconds [95% CI 15.4-30.8] vs. mean 135.4 seconds [95% CI 130.2-150.6]). However, the locking pliers technique destroyed all rings and caused sharp ring fragments to be thrown up to 37 in. CONCLUSIONS: Both the umbilical tape or string technique and the locking pliers technique successfully removed tungsten carbide rings in our model. The locking pliers technique is significantly faster but destroys the ring and creates potentially harmful shrapnel.

Opportunistic decision making and complexity in emergency care.

In critical care environments such as the emergency department (ED), many activities and decisions are not planned. In this study, we developed a new methodology for systematically studying what are these unplanned activities and decisions. This methodology expands the traditional naturalistic decision making (NDM) frameworks by explicitly identifying the role of environmental factors in decision making. We focused on decisions made by ED physicians as they transitioned between tasks. Through ethnographic data collection, we developed a taxonomy of decision types. The empirical data provide important insight to the complexity of the ED environment by highlighting adaptive behavior in this intricate milieu. Our results show that half of decisions in the ED we studied are not planned, rather decisions are opportunistic decision (34%) or influenced by interruptions or distractions (21%). What impacts these unplanned decisions have on the quality, safety, and efficiency in the ED environment are important research topics for future investigation.

Duty hours in emergency medicine: balancing patient safety, resident wellness, and the resident training experience: a consensus response to the 2008 institute of medicine resident duty hours recommendations.

Representatives of emergency medicine (EM) were asked to develop a consensus report that provided a review of the past and potential future effects of duty hour requirements for EM residency training. In addition to the restrictions made in 2003 by the Accreditation Council for Graduate Medical Education (ACGME), the potential effects of the 2008 Institute of Medicine (IOM) report on resident duty hours were postulated. The elements highlighted include patient safety, resident wellness, and the resident training experience. Many of the changes and recommendations did not affect EM as significantly as other specialties. Current training standards in EM have already emphasized patient safety by requiring continuous on-site supervision of residents. Resident fatigue has been addressed with restrictions of shift lengths and limitation of consecutive days worked. One recommendation from the IOM was a required 5-hour rest period for residents on call. Emergency department (ED) patient safety becomes an important concern with the decrease in the availability and in the patient load of a resident consultant that may result from this recommendation. Of greater concern is the already observed slower throughput time for admitted patients waiting for resident care, which will increase ED crowding and decrease patient safety in academic institutions. A balance between being overly prescriptive with duty hour restrictions and trying to improve resident wellness was recommended. Discussion is included regarding the appropriate length of EM training programs if clinical experiences were limited by new duty hour regulations. Finally, this report presents a review of the financing issues associated with any changes.

Duty hours in emergency medicine: balancing patient safety, resident wellness, and the resident training experience: a consensus response to the 2008 Institute of Medicine resident duty hours recommendations.

BACKGROUND: Representatives of emergency medicine (EM) were asked to develop a consensus report that provided a review of the past and potential future effects of duty hour requirements for EM residency training. In addition to the restrictions made in 2003 by the Accreditation Council for Graduate Medical Education, the potential effects of the 2008 Institute of Medicine (IOM) report on resident duty hours were postulated. DISCUSSION: The elements highlighted include patient safety, resident wellness, and the resident training experience. Many of the changes and recommendations did not affect EM as significantly as other specialties. Current training standards in EM have already emphasized patient safety by requiring continuous onsite supervision of residents. Resident fatigue has been addressed with restrictions of shift lengths and limitation of consecutive days worked. CONCLUSION: One recommendation from the IOM was a required 5-h rest period for residents on call. Emergency department (ED) patient safety becomes an important concern with the decrease in the availability and in the patient load of a resident consultant that may result from this recommendation. Of greater concern is the already observed slower throughput time for admitted patients waiting for resident care, which will increase ED crowding and decrease patient safety in academic institutions. A balance between being overly prescriptive with duty hour restrictions and trying to improve resident wellness was recommended. Discussion is included regarding the appropriate length of EM training programs if clinical experiences were limited by new duty hour regulations. Finally, this report presents a review of the financing issues associated with any changes.

The future of emergency medicine.

BACKGROUND: The specialty of emergency medicine (EM) continues to experience a significant workforce shortage in the face of increasing demand for emergency care. SUMMARY: In July 2009, representatives of the leading EM organizations met in Dallas for the Future of Emergency Medicine Summit. Attendees at the Future of Emergency Medicine Summit agreed on the following: 1) Emergency medical care is an essential community service that should be available to all; 2) An insufficient emergency physician workforce also represents a potential threat to patient safety; 3) Accreditation Council for Graduate Medical Education/American Osteopathic Association (AOA)-accredited EM residency training and American Board of Medical Specialties/AOA EM board certification is the recognized standard for physician providers currently entering a career in emergency care; 4) Physician supply shortages in all fields contribute to-and will continue to contribute to-a situation in which providers with other levels of training may be a necessary part of the workforce for the foreseeable future; 5) A maldistribution of EM residency-trained physicians persists, with few pursuing practice in small hospital or rural settings; 6) Assuring that the public receives high quality emergency care while continuing to produce highly skilled EM specialists through EM training programs is the challenge for EM's future; 7) It is important that all providers of emergency care receive continuing postgraduate education.

The future of emergency medicine.

Physician shortages are being projected for most medical specialties. The specialty of emergency medicine continues to experience a significant workforce shortage in the face of increasing demand for emergency care. The limited supply of emergency physicians, emergency nurses, and other resources is creating an urgent, untenable patient care problem. In July 2009, representatives of the leading emergency medicine organizations met in Dallas, TX, for the Future of Emergency Medicine Summit. This consensus document, agreed to and cowritten by all participating organizations, describes the substantive issues discussed and provides a foundation for the future of the specialty.