Citations

AbstractThe Patient‐Centered Outcomes Research Institute (PCORI) was established by Congress in 2010 to promote the conduct of research that could better inform patients in making decisions that reflect their desired health outcomes. PCORI has established five national priorities for research around which specific funding opportunities are issued: 1) assessment of prevention, diagnosis, and treatment options; 2) improving healthcare systems; 3) communication and dissemination research; 4) addressing disparities; and 5) improving methods for conducting patient‐centered outcomes research. To date, implementation of patient‐centered research in the emergency care setting has been limited, in part because of perceived challenges in meeting PCORI priorities such as the need to focus on a specific disease state or to have planned follow up. We suggest that these same factors that have been seen as challenges to performing patient‐centered research within the emergency setting are also potential strengths to be leveraged to conduct PCORI research. This paper explores factors unique to patient‐centered emergency care research and highlights specific areas of potential alignment within each PCORI priority.

Significance HIV-1 requires integration for efficient gene expression, and the local chromatin environment significantly influences the level of HIV-1 transcription. Silent, integrated proviruses constitute the latent HIV reservoir. As HIV-1 commandeers cellular factors to dictate its preferred integration sites, these interactions consequentially influence latency. We examined the impact of polyadenylation specificity factor CPSF6, which binds HIV-1 capsid, and the integrase-binding chromatin reader LEDGF/p75 on viral infection and integration site distribution. Integration sites were determined in cells knocked down or knocked out for one or both host factors. Our data indicate that CPSF6 directs HIV-1 to transcriptionally active chromatin, where LEDGF/p75 predominantly directs the positions of integration within genes. These findings clarify the roles of cellular forces that dictate HIV-1 integration preferences and hence virus pathogenesis.

Abstract This study evaluated the conventional imaging performance of a research whole-body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x-ray photon flux.

Objectives The purpose of this work was to measure and compare the iodine contrast-to-noise ratio (CNR) between a commercial energy-integrating detector (EID) computed tomography (CT) system and a photon-counting detector (PCD) CT scanner capable of human imaging at clinical dose rates, as well as to determine clinical feasibility using human cadavers. Materials and Methods A research dual-source PCD-CT scanner was used, where the “A” tube/detector subsystem used an EID and the “B” tube/detector subsystem used a PCD. Iodine CNR was measured in 4 anthropomorphic phantoms, simulating 4 patient sizes, at 4 tube potential settings. After biospecimen committee approval, PCD scans were performed on a fresh-frozen human head and a whole-body cadaver using clinical dose rates. Scans were repeated using the EID and identical parameters, and qualitative side-by-side comparisons were performed. Results For the same photon fluence, phantom measurements demonstrated a mean increase in CNR of 11%, 23%, 31%, 38% for the PCD system, relative to the EID system, at 80, 100, 120, and 140 kV, respectively. Photon-counting detector CT additionally provided energy-selective imaging, where low- and high-energy images reflected the energy dependence of the iodine signal. Photon-counting detector images of cadaveric anatomy demonstrated decreased beam hardening and calcium blooming in the high-energy bin images and increased contrast in the low-energy bins images relative to the EID images. Threshold-based PCD images were qualitatively deemed equivalent in other aspects. Conclusions The evaluated research PCD-CT system was capable of clinical levels of image quality at clinical dose rates. It further provided improved CNR relative to state-of-the-art EID-CT. The energy-selective bin images provide further opportunity for dual-energy and multienergy analyses.

AbstractObjectivesThe objective was to describe perceptions of practicing emergency physicians (EPs) regarding the appropriateness and medicolegal implications of using shared decision‐making (SDM) in the emergency department (ED).MethodsWe conducted a cross‐sectional survey of EPs at a large, national professional meeting to assess perceived appropriateness of SDM for different categories of ED management (e.g., diagnostic testing, treatment, disposition) and in common clinical scenarios (e.g., low‐risk chest pain, syncope, minor head injury). A 21‐item survey instrument was iteratively developed through review by content experts, cognitive testing, and pilot testing. Descriptive and multivariate analyses were conducted.ResultsWe approached 737 EPs; 709 (96%) completed the survey. Two‐thirds (67.8%) of respondents were male; 51% practiced in an academic setting and 44% in the community. Of the seven management decision categories presented, SDM was reported to be most frequently appropriate for deciding on invasive procedures (71.5%), computed tomography (CT) scanning (56.7%), and post‐ED disposition (56.3%). Among the specific clinical scenarios, use of thrombolytics for acute ischemic stroke was felt to be most frequently appropriate for SDM (83.4%), followed by lumbar puncture to rule out subarachnoid hemorrhage (73.8%) and CT head for pediatric minor head injury (69.9%). Most EPs (66.8%) felt that using and documenting SDM would decrease their medicolegal risk while a minority (14.2%) felt that it would increase their risk.ConclusionsAcceptance of SDM among EPs appears to be strong across management categories (diagnostic testing, treatment, and disposition) and in a variety of clinical scenarios. SDM is perceived by most EPs to be medicolegally protective.

Abstract Objectives This was a systematic review and meta‐analysis to evaluate the incidence of adverse events in adults undergoing procedural sedation in the emergency department ( ED ). Methods Eight electronic databases were searched, including MEDLINE , EMBASE , EBSCO , CINAHL , CENTRAL , Cochrane Database of Systematic Reviews, Web of Science, and Scopus, from January 2005 through 2015. Randomized controlled trials and observational studies of adults undergoing procedural sedation in the ED that reported a priori selected outcomes and adverse events were included. Meta‐analysis was performed using a random‐effects model and reported as incidence rates with 95% confidence intervals ( CI s). Results The search yielded 2,046 titles for review. Fifty‐five articles were eligible, including 9,652 procedural sedations. The most common adverse event was hypoxia, with an incidence of 40.2 per 1,000 sedations (95% CI = 32.5 to 47.9), followed by vomiting with 16.4 per 1,000 sedations (95% CI = 9.7 to 23.0) and hypotension with 15.2 per 1,000 sedations (95% CI = 10.7 to 19.7). Severe adverse events requiring emergent medical intervention were rare, with one case of aspiration in 2,370 sedations (1.2 per 1,000), one case of laryngospasm in 883 sedations (4.2 per 1,000), and two intubations in 3,636 sedations (1.6 per 1,000). The incidence of agitation and vomiting were higher with ketamine (164.1 per 1,000 and 170.0 per 1,000, respectively). Apnea was more frequent with midazolam (51.4 per 1,000), and hypoxia was less frequent in patients who received ketamine/propofol compared to other combinations. The case of laryngospasm was in a patient who received ketamine, and the aspiration and intubations were in patients who received propofol. When propofol and ketamine are combined, the incidences of agitation, apnea, hypoxia, bradycardia, hypotension, and vomiting were lower compared to each medication separately. Conclusions Serious adverse events during procedural sedation like laryngospasm, aspiration, and intubation are exceedingly rare. Quantitative risk estimates are provided to facilitate shared decision‐making, risk communication, and informed consent.