Efficacy and Impact of a Multimodal Intervention on CT Pulmonary Angiography Ordering Behavior in the Emergency Department.

OBJECTIVE: To evaluate the efficacy of a multimodal intervention in reducing CT pulmonary angiography (CTPA) overutilization in the evaluation of suspected pulmonary embolism in the emergency department (ED). METHODS: Previous mixed-methods analysis of barriers to guideline-concordant CTPA ordering results was used to develop a provider-focused behavioral intervention consisting of a clinical decision support tool and an audit and feedback system at a multisite, tertiary academic network. The primary outcome (guideline concordance) and secondary outcomes (yield and CTPA and D-dimer order rates) were compared using a pre- and postintervention design. ED encounters for adult patients from July 5, 2017, to January 3, 2019, were included. Fisher's exact tests and statistical process control charts were used to compare the pre- and postintervention groups for each outcome. RESULTS: Of the 201,912 ED patient visits evaluated, 3,587 included CTPA. Guideline concordance increased significantly after the intervention, from 66.9% to 77.5% (P < .001). CTPA order rate and D-dimer order rate also increased significantly, from 17.1 to 18.4 per 1,000 patients (P = .035) and 30.6 to 37.3 per 1,000 patients (P < .001), respectively. Percent yield showed no significant change (12.3% pre- versus 10.8% postintervention; P = .173). Statistical process control analysis showed sustained special-cause variation in the postintervention period for guideline concordance and D-dimer order rates, temporary special-cause variation for CTPA order rates, and no special-cause variation for percent yield. CONCLUSION: Our success in increasing guideline concordance demonstrates the efficacy of a mixed-methods, human-centered approach to behavior change. Given that neither of the secondary outcomes improved, our results may demonstrate potential limitations to the guidelines directing the ordering of CTPA studies and D-dimer ordering.

A series of caged fluorophores for calibrating light intensity.

Absolute measurement of light intensity is sought for in multiple areas of chemistry, biology, physics, and engineering. It can be achieved by using an actinometer from analyzing the time-course of its reaction extent on applying constant light. However, most reported actinometers exploit the absorbance observable for reporting the reaction extent, which is not very sensitive nor relevant in imaging systems. In this work, we report a series of hydrophobic and hydrophilic caged fluorophores that overcome the preceding limitations. Based on the robust pyranine backbone, they can easily be synthesized on a large scale in one to a few steps. Their brightness increases over illumination and their uncaging cross-sections have been thoroughly characterized upon one- and two-photon excitation. As a demonstration of their use, we calibrated light intensity in various chemical and biological samples, which have been observed with epifluorescence and confocal imaging systems.

Near-infrared co-illumination of fluorescent proteins reduces photobleaching and phototoxicity.

Here we present a method to reduce the photobleaching of fluorescent proteins and the associated phototoxicity. It exploits a photophysical process known as reverse intersystem crossing, which we induce by near-infrared co-illumination during fluorophore excitation. This dual illumination method reduces photobleaching effects 1.5-9.2-fold, can be easily implemented on commercial microscopes and is effective in eukaryotic and prokaryotic cells with a wide range of fluorescent proteins.

Post-Discharge Health Status and Symptoms in Patients with Severe COVID-19.

BACKGROUND: Little is known about long-term recovery from severe COVID-19 disease. Here, we characterize overall health, physical health, and mental health of patients 1 month after discharge for severe COVID-19. METHODS: This was a prospective single health system observational cohort study of patients ≥ 18 years hospitalized with laboratory-confirmed COVID-19 disease who required at least 6 l of oxygen during admission, had intact baseline cognitive and functional status, and were discharged alive. Participants were enrolled between 30 and 40 days after discharge. Outcomes were elicited through validated survey instruments: the PROMIS® Dyspnea Characteristics and PROMIS® Global Health-10. RESULTS: A total of 161 patients (40.6% of eligible) were enrolled; 152 (38.3%) completed the survey. Median age was 62 years (interquartile range [IQR], 50-67); 57 (37%) were female. Overall, 113/152 (74%) participants reported shortness of breath within the prior week (median score 3 out of 10 [IQR 0-5]), vs 47/152 (31%) pre-COVID-19 infection (0, IQR 0-1), p < 0.001. Participants also rated their physical health and mental health as worse in their post-COVID state (43.8, standard deviation 9.3; mental health 47.3, SD 9.3) compared to their pre-COVID state, (54.3, SD 9.3; 54.3, SD 7.8, respectively), both p < 0.001. Physical and mental health means in the general US population are 50 (SD 10). A total of 52/148 (35.1%) patients without pre-COVID oxygen requirements needed home oxygen after hospital discharge; 20/148 (13.5%) reported still using oxygen at time of survey. CONCLUSIONS: Patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health, and mental health for at least several weeks after hospital discharge.

Post-discharge health status and symptoms in patients with severe COVID-19.

BACKGROUND: Little is known about long-term recovery from severe COVID-19 disease. Here, we characterize overall health, physical health and mental health of patients one month after discharge for severe COVID-19. METHODS: This was a prospective single health system observational cohort study of patients ≥18 years hospitalized with laboratory-confirmed COVID-19 disease who required at least 6 liters of oxygen during admission, had intact baseline cognitive and functional status and were discharged alive. Participants were enrolled between 30 and 40 days after discharge. Outcomes were elicited through validated survey instruments: the PROMIS Dyspnea Characteristics and PROMIS Global Health-10. RESULTS: A total of 161 patients (40.6% of eligible) were enrolled; 152 (38.3%) completed the survey. Median age was 62 years (interquartile range [IQR], 50-67); 57 (37%) were female. Overall, 113/152 (74%) participants reported shortness of breath within the prior week (median score 3 out of 10 [IQR 0-5]), vs. 47/152 (31%) pre-COVID-19 infection (0, IQR 0-1), p<0.001. Participants also rated their physical health and mental health as worse in their post-COVID state (43.8, standard deviation 9.3; mental health 47.3, SD 9.3) compared to their pre-COVID state, (54.3, SD 9.3; 54.3, SD 7.8, respectively), both p <0.001. A total of 52/148 (35.1%) patients without pre-COVID oxygen requirements needed home oxygen after hospital discharge; 20/148 (13.5%) reported still using oxygen at time of survey. CONCLUSIONS: Patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health and mental health for at least several weeks after hospital discharge.

Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19.

OBJECTIVE: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4-2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6-2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Fast stimulated Raman and second harmonic generation imaging for intraoperative gastro-intestinal cancer detection.

Conventional haematoxylin, eosin and saffron (HES) histopathology, currently the 'gold-standard' for pathological diagnosis of cancer, requires extensive sample preparations that are achieved within time scales that are not compatible with intra-operative situations where quick decisions must be taken. Providing to pathologists a close to real-time technology revealing tissue structures at the cellular level with HES histologic quality would provide an invaluable tool for surgery guidance with evident clinical benefit. Here, we specifically develop a stimulated Raman imaging based framework that demonstrates gastro-intestinal (GI) cancer detection of unprocessed human surgical specimens. The generated stimulated Raman histology (SRH) images combine chemical and collagen information to mimic conventional HES histopathology staining. We report excellent agreements between SRH and HES images acquire on the same patients for healthy, pre-cancerous and cancerous colon and pancreas tissue sections. We also develop a novel fast SRH imaging modality that captures at the pixel level all the information necessary to provide instantaneous SRH images. These developments pave the way for instantaneous label free GI histology in an intra-operative context.

An Evaluation of Guideline-Discordant Ordering Behavior for CT Pulmonary Angiography in the Emergency Department.

PURPOSE: The aim of this study was to determine rates of and possible reasons for guideline-discordant ordering of CT pulmonary angiography for the evaluation of suspected pulmonary embolism (PE) in the emergency department. METHODS: A retrospective review was performed of 212 consecutive encounters (January 6, 2016, to February 25, 2016) with 208 unique patients in the emergency department that resulted in CT pulmonary angiography orders. For each encounter, the revised Geneva score and two versions of the Wells criteria were calculated. Each encounter was then classified using a two-tiered risk stratification method (PE unlikely versus PE likely). Finally, the rate of and possible explanations for guideline-discordant ordering were assessed via in-depth chart review. RESULTS: The frequency of guideline-discordant studies ranged from 53 (25%) to 79 (37%), depending on the scoring system used; 46 (22%) of which were guideline discordant under all three scoring systems. Of these, 18 (39%) had at least one patient-specific factor associated with increased risk for PE but not included in the risk stratification scores (eg, travel, thrombophilia). CONCLUSIONS: Many of the guideline-discordant orders were placed for patients who presented with evidence-based risk factors for PE that are not included in the risk stratification scores. Therefore, guideline-discordant ordering may indicate that in the presence of these factors, the assessment of risk made by current scoring systems may not align with clinical suspicion.

Automated Pulmonary Embolism Risk Classification and Guideline Adherence for Computed Tomography Pulmonary Angiography Ordering.

BACKGROUND: The assessment of clinical guideline adherence for the evaluation of pulmonary embolism (PE) via computed tomography pulmonary angiography (CTPA) currently requires either labor-intensive, retrospective chart review or prospective collection of PE risk scores at the time of CTPA order. The recording of clinical data in a structured manner in the electronic health record (EHR) may make it possible to automate the calculation of a patient's PE risk classification and determine whether the CTPA order was guideline concordant. OBJECTIVES: The objective of this study was to measure the performance of automated, structured data-only versions of the Wells and revised Geneva risk scores in emergency department (ED) encounters during which a CTPA was ordered. The hypothesis was that such an automated method would classify a patient's PE risk with high accuracy compared to manual chart review. METHODS: We developed automated, structured data-only versions of the Wells and revised Geneva risk scores to classify 212 ED encounters during which a CTPA was performed as "PE likely" or "PE unlikely." We then combined these classifications with D-dimer ordering data to assess each encounter as guideline concordant or discordant. The accuracy of these automated classifications and assessments of guideline concordance were determined by comparing them to classifications and concordance based on the complete Wells and revised Geneva scores derived via abstractor manual chart review. RESULTS: The automatically derived Wells and revised Geneva risk classifications were 91.5 and 92% accurate compared to the manually determined classifications, respectively. There was no statistically significant difference between guideline adherence calculated by the automated scores compared to manual chart review (Wells, 70.8% vs. 75%, p = 0.33; revised Geneva, 65.6% vs. 66%, p = 0.92). CONCLUSION: The Wells and revised Geneva score risk classifications can be approximated with high accuracy using automated extraction of structured EHR data elements in patients who received a CTPA. Combining these automated scores with D-dimer ordering data allows for the automated assessment of clinical guideline adherence for CTPA ordering in the ED, without the burden of manual chart review.

Qualitative Study to Understand Ordering of CT Angiography to Diagnose Pulmonary Embolism in the Emergency Room Setting.

PURPOSE: To better understand the decision making behind the ordering of CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE) in the emergency department. METHODS: We conducted semistructured interviews with our institution's emergency medicine (EM) providers and radiologists who read CTPAs performed in the emergency department. We employed the Theoretical Domains Framework-a formal, structured approach used to better understand the motivations and beliefs of physicians surrounding a complex medical decision making-to categorize the themes that arose from our interviews. RESULTS: EM providers were identified as the main drivers of CTPA ordering. Both EM and radiologist groups perceived the radiologist's role as more limited. Experience- and gestalt-based heuristics were the most important factors driving this decision and more important, in many cases, than established algorithms for CTPA ordering. There were contrasting views on the value of d-dimer in the suspected PE workup, with EM providers finding this test less useful than radiologists. EM provider and radiologist suggestions for improving the appropriateness of CTPA ordering consisted of making this process more arduous and incorporating d-dimer tests and prediction rules into a decision support tool. CONCLUSION: EM providers were the main drivers of CTPA ordering, and there was a marginalized role for the radiologist. Experience- and gestalt-based heuristics were the main influencers of CTPA ordering. Our findings suggest that a more nuanced intervention than simply including a d-dimer and a prediction score in each preimaging workup may be necessary to curb overordering of CTPA in patients suspected of PE.

Theory of the development of curved barbs and their effects on feather morphology.

Feathers exhibit an extraordinary diversity of shapes, which are used by birds to accomplish a diverse set of functions. Pennaceous feathers have a double branched morphology that develops from a tube of epidermis, and variation in branch geometry determines feather shape. Feather development is both complex (i.e., a simple developmental modification can have multiple effects on mature feather shape), and redundant (i.e., different developmental modifications can create the same shape). Due to this, it is not readily apparent how different feather shapes develop. In many feathers, barbs are not straight, but instead curve in toward, or away, from the feather tip. Barb curvature can affect the shape of mature feathers but the development of curved barbs is unknown. Previous research has hypothesized that barb curvature could develop either during the helical growth of barb ridges in the tubular feather germ, or during barb angle expansion as the feather unfurls from the sheath. To better understand the development of curved barbs and their effects on mature feathers we present a theoretical model of curved barb development and test the model with empirical investigations of feathers. We find that curved barbs affect many aspects of feather morphology including vane width, barb length, and barb spacing. In real feathers, curved barbs can develop both during helical barb ridge growth and during barb angle expansion, with most of the observed curvature due to barb angle expansion. Our results demonstrate that barb angle expansion as a feather unfurls from the sheath is a complex and dynamic process that plays an important role in determining the shape and structure of mature feathers. Curved barbs create heterogeneity in barb geometry within the feather vane, which could have important implications for aerodynamic function and the development of within feather pigmentation patterns. J. Morphol. 277:995-1013, 2016. © 2016 Wiley Periodicals, Inc.