Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use.

OBJECTIVES: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN: Prospective cohort study. SETTING: Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS: Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS: All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS: Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5-15.7%) in band 1, 28.1% (95% CI, 21.3-35.8%) in band 2, and 49.4% (95% CI, 41.4-57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS: Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.

Clinical characteristics and outcomes of SARS-Cov-2 B.1.1.529 infections in hospitalized patients and multi-surge comparison in Louisiana.

BACKGROUND: Peer reviewed data describing SARS-CoV-2 Omicron variant symptoms and clinical outcomes as compared to prior surges in the United States is thus far limited. We sought to determine disease severity, presenting features, and epidemiologic factors of the SARS-CoV-2 Omicron variant compared to prior surges. METHODS: Retrospective cohort analysis was performed on patients admitted during five surges in Louisiana between March 2020 and January 2022. Patient data was pulled from the medical record and a subset of patients during Surge 5 were manually abstracted. Patients who were admitted to one of six Louisiana hospitals with a positive SARS-CoV-2 test during the 5 defined surge periods were included. Surges were compared using chi-squared tests and one way ANOVA for age, sex, vaccination status, length of stay, ICU status, ventilation requirement, and disposition at discharge. The records of patients admitted during the omicron surge were analyzed for presenting symptoms and incidental SARS-CoV-2 diagnosis. RESULTS: With each subsequent surge, a smaller proportion of patients presenting to the emergency department were admitted. Patients admitted during surge 5 had shorter lengths of stay and fewer comorbidities than prior surges. Fewer patients in surge 5 presented with a respiratory condition and fewer required ICU admission. In surges 4 and 5, fewer vaccinated patients were admitted compared to their unvaccinated counterparts. Overall mortality was lower in surge 5 (9%) than in surge 4 (15%) p < .0005. Of the SARS-Cov-2 admissions in surge 5, 22.3% were felt to be incidental diagnoses. CONCLUSIONS: As the COVID-19 pandemic progressed, a younger and less vaccinated population was associated with higher risk for severe disease, fewer patients required ICU admission and overall mortality decreased. Vaccinations seemed to be protective for overall risk of hospitalization but once admitted did not seem to confer additional protection against severe illness during the omicron surge. Age also contributed to patient outcomes.

Effect of Medicaid Expansion on Visit Composition in a Louisiana Health Care System.

Background: In 2016, Louisiana expanded Medicaid to low-income adults under the Patient Protection and Affordable Care Act. By 2020, the uninsured rate of adults in Louisiana had dropped from 22.7% to 8.9%; however, few reports describe the effect Medicaid expansion has had on access and utilization of health care services in Louisiana. Methods: For this study, we collected all-payer emergency department and clinic visits from one health care system in Louisiana from 2015 to 2019. We used a time series analysis to compare trends before and after Medicaid expansion in health insurance coverage and emergency department visit type. Results: The changes in payer mix in the urgent care and primary care clinics and emergency departments after Medicaid expansion was driven by the uptake of Medicaid coverage in the previously uninsured. Medicaid expansion had a limited impact on the number of urgent care and emergent and nonemergent emergency department visits, but an increase in primary care visits was observed. Conclusion: Medicaid expansion reduced uncompensated care in our patient population and expanded the access to primary care clinics. Ongoing research is needed to understand the effect of nonfinancial barriers to care on access to and utilization of services in Louisiana.

Retrospective identification of infection in the emergency department: A significant challenge in sepsis clinical trials.

BACKGROUND: This study examined three methods for retrospectively identifying infection in emergency department (ED) patients: modified objective definitions of infection (MODI) from the CDC/NHSN, physician adjudication determination of infection, and ED treating physician behavior. METHODS: This study used a subset of data from a prospective sepsis trial. We used Fleiss's Kappa to compare agreement between two physicians retrospectively adjudicating infection based on the patient's medical record, modified infection definition from the CDC/NHSN, and ED treating physician behavior. RESULTS: Overall, there was similar agreement between physician adjudication of infection and MODI criteria (Kappa=0.59) compared to having two physicians independently identify infection through retrospective chart review (Kappa=0.58). ED treating physician behavior was a poorer proxy for infection when compared to the MODI criteria (0.41) and physician adjudication (Kappa = 0.50). CONCLUSIONS: Retrospective identification of infection poses a significant challenge in sepsis clinical trials. Using modified definitions of infection provides a standardized, less time consuming, and equally effective means of identifying infection compared to having multiple physicians adjudicate a patient's chart.

Reduced turnaround times through multi-sectoral community collaboration during the first surge of SARS-CoV-2 and associated effect on patient care and hospital operations.

BACKGROUND: In March 2020, an influx of admissions in COVID-19 positive patients threatened to overwhelm healthcare facilities in East Baton Rouge Parish, Louisiana. Exacerbating this problem was an overall shortage of diagnostic testing capability at that time, resulting in a delay in time-to-result return. An improvement in diagnostic testing availability and timeliness was necessary to improve the allocation of resources and ultimate throughput of patients. The management of a COVID-19 positive patient or patient under investigation requires infection control measures that can quickly consume personal protective equipment (PPE) stores and personnel available to treat these patients. Critical shortages of both PPE and personnel also negatively impact care in patients admitted with non-COVID-19 illnesses. METHODS: A multisectoral partnership of healthcare providers, facilities and academicians created a molecular diagnostic lab within an academic research facility dedicated to testing inpatients and healthcare personnel for SARS-CoV-2. The purpose of the laboratory was to provide a temporary solution to the East Baton Rouge Parish healthcare community until individual facilities were self-sustaining in testing capabilities. We describe the partnership and the impacts of this endeavor by developing a model derived from a combination of data sources, including electronic health records, hospital operations, and state and local resources. FINDINGS: Our model demonstrates two important principles: the impact of reduced turnaround times (TAT) on potential differences in inpatient population numbers for COVID-19 and savings in PPE attributed to the more rapid TAT.

Assessment of a Cellular Host Response Test as a Sepsis Diagnostic for Those With Suspected Infection in the Emergency Department.

OBJECTIVES: Sepsis is a common cause of morbidity and mortality. A reliable, rapid, and early indicator can help improve efficiency of care and outcomes. To assess the IntelliSep test, a novel in vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes, as a rapid diagnostic for sepsis and a measure of severity of illness, as defined by Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation-II scores and the need for hospitalization. DESIGN SETTING SUBJECTS: Adult patients presenting to two emergency departments in Baton Rouge, LA, with signs of infection (two of four systemic inflammatory response syndrome criteria, with at least one being aberration of temperature or WBC count) or suspicion of infection (a clinician order for culture of a body fluid), were prospectively enrolled. Sepsis status, per Sepsis-3 criteria, was determined through a 3-tiered retrospective and blinded adjudication process consisting of objective review, site-level clinician review, and final determination by independent physician adjudicators. MEASUREMENTS AND MAIN RESULTS: Of 266 patients in the final analysis, those with sepsis had higher IntelliSep Index (median = 6.9; interquartile range, 6.1-7.6) than those adjudicated as not septic (median = 4.7; interquartile range, 3.7-5.9; p < 0.001), with an area under the receiver operating characteristic curve of 0.89 and 0.83 when compared with unanimous and forced adjudication standards, respectively. Patients with higher IntelliSep Index had higher Sequential Organ Failure Assessment (3 [interquartile range, 1-5] vs 1 [interquartile range, 0-2]; p < 0.001) and Acute Physiology and Chronic Health Evaluation-II (7 [interquartile range, 3.5-11.5] vs 5 [interquartile range, 2-9]; p < 0.05) and were more likely to be admitted to the hospital (83.6% vs 48.3%; p < 0.001) compared with those with lower IntelliSep Index. CONCLUSIONS: In patients presenting to the emergency department with signs or suspicion of infection, the IntelliSep Index is a promising tool for the rapid diagnosis and risk stratification for sepsis.

Simulation-Based Education Enhances Patient Safety Behaviors During Central Venous Catheter Placement.

OBJECTIVE: We describe the effect of simulation-based education on residents' adherence to protocols for and performance of central venous access. METHODS: Internal medicine and emergency medicine residents underwent a central venous access course that included a lecture, video presentation, readings, and simulation demonstrations presented by faculty. Baseline data were collected before the course was initiated. After a skills session where they rehearsed their ultrasound-guided central venous access skills, residents were evaluated using a procedural checklist and written knowledge exam. Residents also completed questionnaires regarding confidence in performing ultrasound-guided central venous access and opinions about the training course. RESULTS: Residents demonstrated significant improvement on the written knowledge exam (P < 0.0001) and Standard Protocol Checklist (P < 0.0001) after the training course. Training improved a number of patient safety elements, including adherence to sterile technique, transparent dressing, discarding sharps, and ordering postprocedure x-rays. However, a number of residents failed to wash their hands, prepare with chlorhexidine, drape the patient using a sterile technique, anesthetize the site, and perform a preprocedure time-out. Significant improvement in procedural skills was also noted for reduction in skin-to-vein time (P < 0.003) as well as a reduction in number of residents who punctured the carotid artery (P < 0.02). CONCLUSIONS: Simulation-based education significantly improved residents' knowledge and procedural skills along with their confidence. Adherence to the protocol also improved. This study illustrates that simulation-based education can improve patient safety through training and protocols.

Large Spontaneous Right Catamenial Pneumothorax with Diaphragmatic Defect and Liver Herniation.

Catamenial pneumothorax is a spontaneous pneumothorax that occurs predominantly women of child bearing age. We describe a case of a 40-year-old nulliparous woman with medical history significant for endometriosis who presented with severe chest tightness of one-day duration. Chest radiography (CXR) showed a large right spontaneous pneumothorax, what was thought to be a 5.6 cm pleural mass at the right lung base. Following pneumothorax diagnosis, the patient underwent emergent right thoracostomy with pigtail catheter placement. A repeat CXR revealed marked re-expansion of the lung but persistence of a right pleural mass. Follow up computed tomography scan of the chest showed a 33 mm diaphragmatic defect with 5.8 x 4.6 x 3.9 cm area of herniated liver corresponding to the presumed pleural mass. Following complete thoracic imaging, patient underwent video-assisted thoracoscopic surgery, mechanical pleurodesis, and open repair of the right diaphragmatic defect. Intraoperatively, an endometrial implant was noted on the chest wall. On postoperative day three, she began her menstrual cycle and was evaluated by gynecologist who recommended hormonal therapy to reduce risk of recurrent pneumothorax. Due to a persistent air leak, the chest tube was transitioned to a Heimlich valve to facilitate home discharge. The patient was discharged on postoperative day eight, seen as outpatient with resolution of air leak and removal of chest tube.

Residents' Preferences and Performance of Three Techniques for Ultrasound-Guided Central Venous Cannulation After Simulation Training.

BACKGROUND: Obtaining central venous cannulation of the internal jugular vein is an important skill for physicians to master. To our knowledge, no studies to date have examined residents' preferences or the safety of the oblique approach compared to other approaches. This study compared medical residents' preferences for and performance of ultrasound-guided central venous access using the transverse, longitudinal, and oblique approaches. METHODS: Emergency medicine and internal medicine residents (n = 72) at an urban community hospital participated in a central venous access course. To assess the residents' preferences, residents were asked to rank the transverse, longitudinal, and oblique approaches as first, second, or third. In addition to preference, skin-to-vein time, carotid artery puncture, and successful completion on the first attempt during a final skills analysis were measured. RESULTS: During the final skills analysis, the majority (87.5%) of residents preferred the transverse approach. The oblique approach had a significantly larger proportion of failures of technique than the transverse approach (P = 0.02). No significant differences in successful cannulation on the first attempt, skin-to-vein time, or carotid artery puncture among the 3 approaches were found during the final skills assessment. CONCLUSION: The majority of residents preferred the transverse approach to the longitudinal and oblique approaches. Although no significant differences among the 3 approaches were found in performance measures, more failures of technique occurred with the oblique approach. This study suggests that novices may require in-depth training and supervision to become proficient with the oblique approach.

Practically Saline.

Introduction. In December 2014, the Food and Drug Administration issued a recall of all Wallcur simulation products due to reports of their use in clinical practice. We present a case of septic shock and multiorgan failure after the accidental intravenous infusion of a nonsterile Wallcur simulation product. Case. The patient presented with symptoms of rigors and dyspnea occurring immediately after infusion of Wallcur Practi-0.9% saline. Initial laboratory evidence was consistent with severe septic shock and multiorgan dysfunction. His initial lactic acid level was 9 mmol/L (reference range = 0.5-2.2), and he had evidence of acute kidney injury and markers of disseminated intravascular coagulation. All 4 blood culture bottles isolated multidrug-resistant Empedobacter brevis. The patient recovered from his illness and was discharged with ciprofloxacin therapy per susceptibilities. Discussion. This patient represents the first described case of severe septic shock associated with the infusion of a Wallcur simulation product. Intravenous inoculation of a nonsterile fluid is rare and exposes the patient to unusual environmental organisms, toxins, or unsafe fluid characteristics such as tonicity. During course of treatment, we identified the possible culprit to be a multidrug-resistant isolate of Empedobacter brevis. We also discuss the systemic failures that led to this outbreak.

Neutrophil-mediated lung permeability and host defense proteins.

Neutrophil recruitment to the alveolar space is associated with increased epithelial permeability. The present study investigated in mice whether neutrophil recruitment to the lung leads to accumulation of plasma-derived host defense proteins in the alveolar space and whether respiratory burst contributes to this increase in permeability. Albumin, complement C1q, and IgM were increased in bronchoalveolar lavage (BAL) fluid 6 h after intratracheal LPS challenge. Neutrophil depletion before LPS treatment completely prevented this increase in BAL fluid protein concentration. Respiratory burst was not detected in neutrophils isolated from BAL fluid, and BAL proteins were increased in mice deficient in a key subunit of the respiratory burst apparatus, gp91(phox), similar to wild-type mice. Neutrophil recruitment elicited by intratracheal instillation of the chemokines macrophage inflammatory protein-2 and keratinocyte-derived chemokine was also accompanied by accumulation of albumin, C1q, and IgM. During neutrophil recruitment to the alveolar space, epithelial permeability facilitates delivery of host defense proteins. The observed increase in epithelial permeability requires recruitment of neutrophils, but not activation of the respiratory burst, and occurs with chemokine-induced neutrophil migration independent of LPS exposure.

Coagulation in sepsis.

Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.