A standardized protocol using clinical adjudication to define true infection status in patients presenting to the emergency department with suspected infections and/or sepsis.

In absence of a "gold standard", a standardized clinical adjudication process was developed for a registrational trial of a transcriptomic host response (HR) test. Two physicians independently reviewed clinical data to adjudicate presence and source of bacterial and viral infections in emergency department patients. Discordant cases were resolved by a third physician. Agreement among 955 cases was 74.1% (708/955) for bacterial, 75.6% (722/955) for viral infections, and 71.2% (680/955) overall. Most discordances were minor (85.2%; 409/480) versus moderate (11.7%; 56/480) or complete (3.3%; 16/480). Concordance levels were lowest for bacterial skin and soft tissue infections (8.2%) and for viral respiratory tract infections (4.5%). This robust adjudication process can be used to evaluate HR tests and other diagnostics by regulatory agencies and for educating clinicians, laboratorians, and clinical researchers. Clinicaltrials.gov NCT04094818. SUMMARY: Without a gold standard for evaluating host response tests, clinical adjudication is a robust reference standard that is essential to determine the true infection status in diagnostic registrational clinical studies.

Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. METHODS: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO2/FiO2 ratio > 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early. RESULTS: The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia. CONCLUSIONS: Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted. Trial registration NCT04345614.

Initial clinical experience with the Quantra QStat System in adult trauma patients.

BACKGROUND: Whole blood viscoelastic testing (VET) devices are routinely used in a variety of clinical settings to assess hemostasis. The Quantra QStat System is a cartridge-based point of care VET device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance. The objective of this study was to assess the ability of the Quantra QStat System to detect coagulopathies in trauma patients. METHODS: A multicenter observational study was conducted on adult subjects at two level 1 trauma centers. For each subject, whole blood samples were drawn upon arrival to the emergency department and again, in some cases, after administration of blood products and/or antifibrinolytics. Samples were analyzed on the Quantra in parallel to ROTEM delta. The QStat cartridge provides measures of Clot Time (CT), Clot Stiffness (CS), Fibrinogen and Platelet Contributions to clot stiffness (FCS and PCS), and Clot Stability to Lysis (CSL). Data analyses included linear regression of Quantra and ROTEM parameters and an assessment of the concordance of the two devices for the assessment of hyperfibrinolysis. RESULTS: A total of 56 patients were analyzed. 42% of samples had a low QStat CS value suggestive of an hypocoagulable state. The low stiffness values could be attributed to either low PCS, FCS or combination. Additionally, 13% of samples showed evidence of hyperfibrinolysis based on the QStat CSL parameter. Samples analyzed with ROTEM assays showed a lower prevalence of low CS and hyperfibrinolysis based on EXTEM and FIBTEM results. The correlation of CS, FCS and CT versus equivalent ROTEM parameters was strong with r-values of 0.83, 0.79 and 0.79, respectively. DISCUSSION: This first clinical experience with the Quantra in trauma patients showed that the QStat Cartridge was strongly correlated with ROTEM parameters and that it could detect coagulopathies associated with critical bleeding. LEVEL OF EVIDENCE: Diagnostic test, Level II.

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE).

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED). METHODS: This exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+ ) from baseline until 4 hours after start of dosing. RESULTS: Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was -0.41 (±0.11) mmol/L and -0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = -0.13 mmol/L, 95% confidence interval [CI] = -0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: -0.72 (±0.12) versus -0.36 (±0.11) mmol/L (LSM difference = -0.35 mmol/L, 95% CI = -0.68 to -0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours. CONCLUSIONS: This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.

The Quick and Dirty: A Tetanus Case Report.

Tetanus is an increasingly rare diagnosis in the post-vaccination era, although it continues to have significant morbidity and mortality worldwide. In the United States (U.S.), the incidence of tetanus has declined dramatically due to the widespread use of the vaccine. High-risk populations for tetanus in the U.S. include the elderly, diabetics, injection drug users, and unvaccinated individuals. This is a report of a 78-year-old male with an incomplete immunization history who presented to an emergency department with jaw pain and who was ultimately diagnosed with tetanus. This report highlights the importance of prompt diagnosis, treatment, and prevention of tetanus.

Triage of Mild Head-Injured Intoxicated Patients Could Be Aided by Use of an Electroencephalogram-Based Biomarker.

OBJECTIVE: Drug and alcohol (DA)-related emergency department (ED) visits represent an increasing fraction the head-injured population seen in the ED. Such patients present a challenge to the evaluation of head injury and determination of need for computed tomographic (CT) scan and further clinical path. This effort examined whether an electroencephalogram (EEG)-based biomarker could aid in reducing unnecessary CT scans in the intoxicated ED population. METHOD: This is a retrospective secondary study of an independent prospective US Food and Drug Administration validation trial that demonstrated the efficacy of (1) an automatic Structural Injury Classifier for the likelihood of injury visible on a CT (CT+) and (2) an EEG-based Brain Function Index to assess functional impairment in minimally impaired, head-injured adults presenting within 3 days of injury. Impact on the biomarker performance in patients who presented with or without DA was studied. RESULTS: Structural Injury Classifier sensitivity was not significantly impacted by the presence of DA. Although specificity decreased, it remained several times higher than obtained using standard CT decision rules. Furthermore, the potential to reduce the number of unnecessary scans by approximately 30% was demonstrated when the Structural Injury Classifier was integrated into CT clinical triage. The Brain Function Index was demonstrated to be independent of the presence of DA. CONCLUSION: This EEG-based assessment technology used to identify the likelihood of structural or functional brain injury in mildly head-injured patients represents an objective way to aid in triage patients with DA on presentation, with the potential to decrease overscanning while not sacrificing sensitivity to injuries visible on CT.

Emergency Department Time Course for Mild Traumatic Brain Injury Workup.

INTRODUCTION: Mild traumatic brain injury (mTBI) is a common cause for visits to the emergency department (ED). The actual time required for an ED workup of a patient with mTBI in the United States is not well known. National emergency medicine organizations have recommended reducing unnecessary testing, including head computed tomography (CT) for these patients.10. METHODS: To examine this issue, we developed a care map that included each step of evaluation of mTBI (Glasgow Coma Scale Score 13-15) - from initial presentation to the ED to discharge. Time spent at each step was estimated by a panel of United States emergency physicians and nurses. We subsequently validated time estimates using retrospectively collected, real-time data at two EDs. Length of stay (LOS) time differences between admission and discharged patients were calculated for patients being evaluated for mTBI. RESULTS: Evaluation for mTBI was estimated at 401 minutes (6.6 hours) in EDs. Time related to head CT comprised about one-half of the total LOS. Real-time data from two sites corroborated the estimate of median time difference between ED admission and discharge, at 6.3 hours for mTBI. CONCLUSION: Limiting use of head CT as part of the workup of mTBI to more serious cases may reduce time spent in the ED and potentially improve overall ED throughput.

Identification of acute stroke using quantified brain electrical activity.

OBJECTIVES: Acute stroke is a leading cause of brain injury and death and requires rapid and accurate diagnosis. Noncontrast head computed tomography (CT) is the first line for diagnosis in the emergency department (ED). Complicating rapid triage are presenting conditions that clinically mimic stroke. There is an extensive literature reporting clinical utility of brain electrical activity in early diagnosis and management of acute stroke. However, existing technologies do not lend themselves to easily acquired rapid evaluation. This investigation used an independently derived classifier algorithm for the identification of traumatic structural brain injury based on brain electrical activity recorded from a reduced frontal montage to explore the potential clinical utility of such an approach in acute stroke assessment. METHODS: Adult patients (age 18 to 95 years) presenting with stroke-like and/or altered mental status symptoms were recruited from urban academic EDs as part of a large research study evaluating the clinical utility of quantitative brain electrical activity in acutely brain-injured patients. All patients from the parent study who had confirmed strokes, and a control group of stroke mimics (those with final ED diagnoses of migraine or syncope), were selected for this study. All stroke patients underwent head CT scans. Some patients with negative CTs had further imaging with magnetic resonance imaging (MRI). Ten minutes of electroencephalographic data were acquired on a hand-held device in development, from five frontal electrodes. Data analyses were done offline. A Structural Brain Injury Index (SBII) was derived using an independently developed binary discriminant classification algorithm whose input was specified features of brain electrical activity. The SBII was previously found to have high accuracy in the identification of traumatic brain-injured patients who were found to have brain injury on CT (CT+). This algorithm was applied to patients in this study and used to classify patients as CT+ or not CT+. Performance was assessed using sensitivity, specificity, and negative and positive predictive values (NPV, PPV). RESULTS: Forty-eight stroke patients (31 ischemic and 17 hemorrhagic) and 135 stroke mimic controls were included. Within the ischemic population, approximately half were CT- but later confirmed for stroke with MRI (CT-/MRI+). Sensitivity to stroke was 91.7%, specificity 50.4% (to stroke mimic), NPV 94.4%, and PPV 39.6%. Eighty percent of the CT-/MRI+ ischemic strokes were correctly identified at the time of the CT- scan. CONCLUSIONS: Despite a small population and the use of a classifier without the benefit of training on a stroke population, these data suggest that a rapidly acquired, easy-to-use system to assess brain electrical activity at the time of evaluation of acute stroke could be a valuable adjunct to current clinical practice.

Clinical features, risk factors, and treatment experience: a review of 74 patients with ST-segment elevation myocardial infarction complicated by ventricular fibrillation.

BACKGROUND: Ventricular fibrillation (VF) is one of the most serious complications of acute myocardial infarction, with a high mortality rate. There is a lack of value of rescue thrombolysis in ST-segment elevation myocardial infarction (STEMI) complicated by VF. OBJECTIVE: To examine the relationship between risk factors and mortality, and assess the value of rescue thrombolysis in STEMI complicated by VF. METHODS: A total 74 cases of STEMI complicated by VF were enrolled. The experimental group consisted of 26 patients who underwent rescue thrombolysis, and the control group included 48 cases without rescue thrombolysis. The two groups were compared in terms of demographic and clinical features including gender, age, onset time, blood pressure, patient's history, creatine kinase-MB, infarct area, complications, therapy, and outcomes, including mortality. RESULTS: The mortality rate of the experimental group was 15.38%, lower than 37.50% of the control group (p < 0.05). The bleeding rate was 34.62% (n = 9) in the experimental group. The risk factors of smoking, shock, and rescue thrombolysis were correlated with mortality of STEMI complicated by VF (p < 0.05 for all): Smoking and shock both were positively correlated with mortality, their regression coefficients/odds ratios (OR) were, respectively, 4606/100,041 and 5552/247,711; the rescue thrombolysis was negatively correlated with mortality, its regression coefficient/OR was -1942/0.143. CONCLUSIONS: Rescue thrombolysis combined with cardiopulmonary resuscitation and defibrillation is beneficial to patients with STEMI complicated by VF. Smoking, shock upon admission, and lack of rescue thrombolysis were risk factors for mortality in STEMI complicated by VF.

Clinical features and treatment experience: a review of 292 Chinese cobra snakebites.

Although Chinese cobra snakebite is the most common type of snake venenation in China, it still lacks a comprehensive and systematic description. Hence, we aimed to study Chinese cobra bite cases with particular attention to demography, epidemiology and clinical profile. In this study, a total of 292 cases of Chinese cobra snakebite, presenting between January 1, 2008 and December 31, 2012, were retrospectively reviewed. To investigate the effect of treatment at different presentation times (time from snakebite to admission), the patients were divided into two groups: group A included 133 cases that presented <12 h after the bite; group B included 159 cases that presented ≥12 h after the bite. To assess the correlation between application of a tourniquet and skin grafting, the cases were re-divided into two groups according to whether or not a tourniquet was used after the snakebite: tourniquet group (n=220) and non-tourniquet group (n=72). The results showed that Chinese cobra snakebites were most commonly seen during the summer, in the upper limbs, and in males, young adults, and snake-hunters. Group A experienced milder intoxication than group B (P<0.001). The rate of skin grafting was significantly higher in the tourniquet group (20.0%, compared with 9.7% in the non-tourniquet group, P<0.05). The results of this study indicate that anti-cobra venom and swift admission (within 12 h of the snakebite) are recommended for Chinese cobra snakebite. Tourniquet use is not recommended.

Use of plasma in the management of central nervous system bleeding: evidence-based consensus recommendations.

INTRODUCTION: Central nervous system (CNS) hemorrhage is a potentially life-threatening condition, especially in patients with acquired coagulopathy. In this setting, treatment of CNS bleeding includes hemostatic therapy to replenish coagulation factors. There is currently a debate over the hemostatic efficacy of plasma in many clinical settings, alongside increasing concern about transfusion-associated adverse events. Despite these concerns, plasma is widely used. Moreover, plasma transfusion practice is variable and there is currently no uniform approach to treatment of traumatic, surgical or spontaneous CNS hemorrhage. This study addresses the need for guidance on the indications and potential risks of plasma transfusion in these settings. An Expert Consensus Panel was convened to develop recommendations guiding the use of plasma to treat bleeding and/or coagulopathy associated with CNS hemorrhage. The panel did not advise on the best treatment available but rather proposed recommendations to be used in the formulation of local procedures to support emergency physicians in their decision-making process. METHODS: Evidence was systematically gathered from the literature and rated using methods established by the Scottish Intercollegiate Guidelines Network. The evidence was used to develop graded consensus recommendations, which are presented along with the evidence-based rationale for each in this report. RESULTS: Sixty-five articles were identified covering both vitamin K antagonist-anticoagulation reversal and treatment of bleeding/coagulopathy in non-anticoagulated patients. Recommendations were then developed in four clinical scenarios within each area, and agreed on unanimously by all members of the panel. CONCLUSION: The Panel considered plasma to be reasonable therapy for CNS hemorrhage requiring urgent correction of coagulopathy, although physicians should be prepared for potential cardiopulmonary complications, and evidence suggests that alternative therapies have superior risk-benefit profiles. Plasma could not be recommended in the absence of hemorrhage or coagulopathy. Consideration of the absolute risks and benefits of plasma therapy before transfusion is imperative.

A training program in portable fluoroscopy for the detection of glass in soft tissues.

OBJECTIVES: The role of emergency department (ED) bedside fluoroscopy is incompletely defined. One potential application is the evaluation of glass foreign bodies (GFBs). We studied the effect of a training intervention on the ability of emergency physicians to detect GFBs in an established chicken leg model. We also studied performance one week after training. METHODS: Assessment of this teaching intervention involved nine emergency medicine residents with minimal prior hands-on fluoroscopy experience. Zero, one, or two clear glass shards no larger than 1.0 mm in any dimension were inserted into fresh chicken legs. Each subject scanned 12 to 15 legs without being given any feedback to determine baseline accuracy. Next, 27 to 30 more legs were immediately scanned with feedback given after each response. Subjects scanned 15 more legs one week later without feedback as follow-up. Data were analyzed using mixed-model analysis of variance. RESULTS: At baseline, overall sensitivity and specificity were 0.40 and 0.61, respectively. At follow-up, sensitivity and specificity were 0.93 and 0.91, respectively. Subjects were significantly more accurate during training and follow-up than at baseline. This level of proficiency reached during training was maintained and continued to improve one week later. CONCLUSIONS: Emergency medicine residents previously inexperienced in fluoroscopy may, through a brief training intervention, acquire the skill to accurately detect small pieces of glass in a chicken leg model, and maintain proficiency one week later. Further studies of emergency department fluoroscopy in GFB management in humans are warranted.

Data Elements for Emergency Department Systems, Release 1.0 (DEEDS): A Summary Report.

See editorial, p 274. Variations in the way that data are entered in emergency department record systems impede the use of ED records for direct patient care and deter their reuse for many other legitimate purposes. To foster more uniform ED data, the Centers for Disease Control and Prevention's National Center for Injury Prevention and Control is coordinating a public-private partnership that has developed recommended specifications for many observations, actions, instructions, conclusions, and identifiers that are entered in ED records. The partnership's initial product, Data Elements for Emergency Department Systems, Release 1.0 (DEEDS), is intended for use by individuals and organizations responsible for ED record systems. If the recommended specifications are widely adopted, then problems-such as data incompatibility and high costs of collecting, linking, and using data-can be substantially reduced. The collaborative effort that led to DEEDS, Release 1.0 sets a precedent for future review and revision of the initial recommendations. [DEEDS Writing Committee: Data Elements for Emergency Department Systems, Release 1.0 (DEEDS): A summary report. Ann Emerg Med February 1998;31:264-273.].

The intermediate snail-host: an agenda for future study

The strategy for the control of schistosomiasis has shifted from one directed towards the interruption of transmission to one of reducing morbidity. As a consequence of this change, it appears prudent to reassess the role of the malacologist and malacology and identify the future direction to be taken by the discipline. The present paper addresses these concerns; first, by reviewing the role of the snail-hosts in the epidemiology and control of schistosomiasis, and, secondly, by suggesting areas for future study. The possible application of newer methods in biotechnology for the resolution of malacological problems are discussed.

Differentiation of the sibling species Biomphalaria occidentalis and Biomphalaria tenagophila by the electrophoretic patterns of their hemoglobin

É descrito um método simples e rápido para distinguir as espécies crípticas Biomphalaria tenagophila e B. occidentalis por eletroforese em gel de agarose. A prova é feita com hemolinfa do molusco, permitindo a cor vermelha da fraçäo hemoglobina visualizar os padröes de migraçäo sem necessidade de recorrer a coloraçöes específicas. Além disso, as amostras de hemolinfa podem ser obtidas sem sacrificar o molusco, que poderá ser usado para outros estudos ou para criaçäo