Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship. Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI. Design, Setting, and Participants: This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc. Interventions: The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection. Main Outcomes and Measures: Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement. Results: Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection. Conclusions and Relevance: In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.

Delayed intracranial hemorrhage in the anticoagulated patient: A systematic review.

BACKGROUND: A significant population of elderly Americans on warfarin is at risk for immediate and delayed intracranial hemorrhage. This qualitative systematic review ascertains the delayed intracranial hemorrhage risk associated with minor head injury and preinjury warfarin use. METHODS: A systematic review using MEDLINE, EMBASE, and the Cochrane Library was performed in August 2014. Cohort studies evaluating delayed intracranial hemorrhage in patients with minor head injuries on warfarin were eligible for inclusion. The definition of delayed hemorrhage was any intracranial bleeding detected subsequent to initial negative brain imaging result following the head injury. Three authors screened and abstracted the data and evaluated methodological quality. Data abstraction also included clinical characteristics that could identify risk factors for delayed intracranial hemorrhage. RESULTS: The search retrieved 294 unique articles, of which 5 studies constituted the final review. The studies included data on 1,257 patients. Among higher-quality studies, the incidence of delayed intracranial hemorrhage ranged from 5.8 to 72 per 1,000 cases of patients on warfarin with minor head injury. Population age was an influential factor in this range of incident rates. International normalized ratio levels had no clear association with individual risk for delayed intracranial hemorrhage. CONCLUSION: The incidence of delayed intracranial hemorrhage is low among patients on warfarin with minor head injury. Trauma centers should consider the characteristics of the population they serve compared with the published studies when determining management strategies for these patients. LEVEL OF EVIDENCE: Systematic review, level III.

Novel Use of Glidescope Indirect Laryngoscopy for Insertion of a Minnesota Tube for Variceal Bleeding.

BACKGROUND: With improvements in endoscopic and interventional radiologic therapies, insertion of gastroesophageal balloon tamponade catheters, commonly known as Sengstaken-Blakemore or Minnesota tubes, is a rarely performed procedure for esophageal or gastric variceal bleeding. In small hospitals or freestanding emergency departments, endoscopic or interventional radiology (IR) therapies might not be available, so patients with exsanguinating variceal bleeding must be stabilized or temporized for transport to larger hospitals. Occasionally, tamponade devices are necessary as a rescue therapy for failed endoscopic or IR therapies or can be used as definitive therapy in select cases. In addition to being rarely performed, there are multiple technical complications associated with blind insertion of tamponade catheters. DISCUSSION: We describe a novel use of indirect laryngoscopy using a Glidescope for assisting in placement of a Minnesota tube in 4 patients with exsanguinating esophageal bleeding. CONCLUSIONS: Insertion of a Minnesota tube for bleeding esophageal or gastric varices is an uncommon, technically challenging procedure that can be lifesaving, and is something emergency physicians, intensivists, and gastroenterologists should be capable of performing. Addition of indirect laryngoscopy may help to improve rapid, safe, and successful placement of these devices.