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.

Pediatric Chest Compression Improvement Via Augmented Reality Cardiopulmonary Resuscitation Feedback in Community General Emergency Departments: A Mixed-Methods Simulation-Based Pilot Study.

BACKGROUND: Yearly, more than 20,000 children experience a cardiac arrest. High-quality pediatric cardiopulmonary resuscitation (CPR) is generally challenging for community hospital teams, where pediatric cardiac arrest is infrequent. Current feedback systems are insufficient. Therefore, we developed an augmented reality (AR) CPR feedback system for use in many settings. OBJECTIVE: We aimed to evaluate whether AR-CPR improves chest compression (CC) performance in non-pediatric-specialized community emergency departments (EDs). METHODS: We performed an unblinded, randomized, crossover simulation-based study. A convenience sample of community ED nonpediatric nurses and technicians were included. Each participant performed three 2-min cycles of CC during a simulated pediatric cardiac arrest. Participants were randomized to use AR-CPR in one of three CC cycles. Afterward, participants participated in a qualitative interview to inquire about their experience with AR-CPR. RESULTS: Of 36 participants, 18 were randomized to AR-CPR in cycle 2 (group A) and 18 were randomized to AR-CPR in cycle 3 (group B). When using AR-CPR, 87-90% (SD 12-13%) of all CCs were in goal range, analyzed as 1-min intervals, compared with 18-21% (SD 30-33%) without feedback (p < 0.001). Analysis of qualitative themes revealed that AR-CPR may be usable without a device orientation, be effective at cognitive offloading, and reduce anxiety around and enhance confidence in the CC delivered. CONCLUSIONS: The novel CPR feedback system, AR-CPR, significantly changed the CC performance in community hospital non-pediatric-specialized general EDs from 18-21% to 87-90% of CC epochs at goal. This study offers preliminary evidence suggesting AR-CPR improves CC quality in community hospital settings.

Characterization and impact of COVID-19-tested and infected patients: Experience of The Johns Hopkins Health System Regional Emergency Departments.

BACKGROUND: There is limited understanding of the characteristics and operational burden of persons under investigation (PUIs) and those testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presenting to emergency departments (EDs). METHODS: We reviewed all adult ED visits to 5 Johns Hopkins Health System hospitals in the Maryland/District of Columbia (DC) region during the initial coronavirus disease 2019 (COVID-19) surge, analyzing SARS-CoV-2 polymerase chain reaction test eligibility, results, demographics, acuity, clinical conditions, and dispositions. RESULTS: Of 27,335 visits, 11,402 (41.7%) were tested and 2484 (21.8%) were SARS-CoV-2 positive. Test-positive rates among Hispanics, Asians, African Americans/Blacks, and Whites were 51.6%, 23.7%, 19.8%, and 12.7% respectively. African American/Blacks infection rates (25.5%-33.8%) were approximately double those of Whites (11.1%-21.1%) in the 3 southern Maryland/DC EDs. Conditions with high test-positive rates were fever (41.9%), constitutional (36.4%), upper respiratory (36.9%), and lower respiratory (31.2%) symptoms. Test-positive rates were similar in all age groups (19.9% to 25.8%), although rates of hospitalization increased successively with age. Almost half, 1103 (44.4%), of test-positive patients required admission, of which 206 (18.7%) were to an ICU. CONCLUSION: The initial surge of SARS-CoV-2 test-positive patients experienced in a regional hospital system had ≈ 42% of patients meeting testing criteria and nearly one-fifth of those testing positive. The operational burden on ED practice, including intense adherence to infection control precautions, cannot be understated. Disproportionately high rates of infection among underrepresented minorities underscores the vulnerability in this population. The high rate of infection among self-identified Asians was unexpected.

Reduction in Emergency Department Presentations in a Regional Health System during the Covid-19 Pandemic.

INTRODUCTION: Nationally, there has been more than a 40% decrease in Emergency Department (ED) patient volume during the coronavirus disease 2019 (Covid-19) crisis, with reports of decreases in presentations of time-sensitive acute illnesses. We analyzed ED clinical presentations in a Maryland/District of Columbia regional hospital system while health mitigation measures were instituted. METHODS: We conducted a retrospective observational cohort study of all adult ED patients presenting to five Johns Hopkins Health System (JHHS) hospitals comparing visits from March 16 through May 15, in 2019 and 2020. We analyzed de-identified demographic information, clinical conditions, and ICD-10 diagnosis codes for year-over-year comparisons. RESULTS: There were 36.7% fewer JHHS ED visits in 2020 compared to 2019 (43,088 vs. 27,293, P<.001). Patients 75+ had the greatest decline in visits (-44.00%, P<.001). Both genders had significant decreases in volume (-41.9%, P<.001 females vs -30.6%, P<.001 males). Influenza like illness (ILI) symptoms increased year-over-year including fever (640 to 1253, 95.8%, P<.001) and shortness of breath (2504 to 2726, 8.9%, P=.002). ICD-10 diagnoses for a number of time-sensitive illnesses decreased including deep vein thrombosis (101 to 39, -61%, P<.001), acute myocardial infarction (157 to 105, -33%, P=.002), gastrointestinal bleeding (290 to 179, -38.3%, P<.001), and strokes (284 to 234, -17.6%, P=0.03). CONCLUSION: ED visits declined significantly among JHHS hospitals despite offsetting increases in ILI complaints. Decreases in presentations of time-sensitive illnesses were of particular concern. Efforts should be taken to inform patients that EDs are safe, otherwise preventable morbidity and mortality will remain a problem.

Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria.

The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs. Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target. Structure-based design led to discovery of N1-hexyl-N5-benzyl-biguanide (HBB), which bound to the CYP3A4 heme with higher affinity than metformin. HBB potently and specifically inhibited CYP3A4 AA epoxygenase activity. HBB also inhibited growth of established ER+ mammary tumors and suppressed intratumoral mTOR. CYP3A4 AA epoxygenase inhibition by biguanides thus demonstrates convergence between eicosanoid activity in mitochondria and biguanide action in cancer, opening a new avenue for cancer drug discovery.