Best Practice Recommendations for Electronic Patient-Reported Outcome Dataset Structure and Standardization to Support Drug Development.

The electronic patient-reported outcome (ePRO) Dataset Structure and Standardization Project is a multistakeholder initiative formed by Critical Path Institute's PRO Consortium and Electronic Clinical Outcome Assessment (eCOA) Consortium to address issues related to ePRO dataset structure and standardization and to provide best practice recommendations for clinical trial sponsors and eCOA providers. Given the many benefits of utilizing electronic modes to capture PRO data, clinical trials are increasingly using these methods, yet there are challenges to using data generated by eCOA systems. Clinical Data Interchange Standards Consortium (CDISC) standards are used in clinical trials to ensure consistency in data collection, tabulation, and analysis and to facilitate regulatory submission. Currently, ePRO data are not required to follow a standard model, and the data models used often vary by eCOA provider and sponsor. This lack of consistency creates risks for programming and analysis and difficulties for analytics functions generating the required analysis and submission datasets. There is a disconnect between data standards used for study data submission and those used for data collection via case report forms and ePRO forms, which would be mitigated through the application of CDISC standards for ePRO data capture and transfer. The project was formed to collate and examine the issues arising from the lack of adoption of standardized approaches and this paper details recommendations to address those issues. Recommendations to address issues with ePRO dataset structure and standardization include adopting CDISC standards in the ePRO data platform, timely involvement of key stakeholders, ensuring ePRO controls are implemented, addressing issues of missing data early in development, ensuring quality control and validation of ePRO datasets, and use of read-only datasets.

Cohort of Four Thousand Four Hundred Four Persons Under Investigation for COVID-19 in a New York Hospital and Predictors of ICU Care and Ventilation.

Study objective: Most coronavirus disease 2019 (COVID-19) reports have focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. However, at initial presentation, most patients' viral status is unknown. Determination of factors that predict initial and subsequent need for ICU and invasive mechanical ventilation is critical for resource planning and allocation. We describe our experience with 4,404 persons under investigation and explore predictors of ICU care and invasive mechanical ventilation at a New York COVID-19 epicenter. Methods: We conducted a retrospective cohort study of all persons under investigation and presenting to a large academic medical center emergency department (ED) in New York State with symptoms suggestive of COVID-19. The association between patient predictor variables and SARS-CoV-2 status, ICU admission, invasive mechanical ventilation, and mortality was explored with univariate and multivariate analyses. Results: Between March 12 and April 14, 2020, we treated 4,404 persons under investigation for COVID-19 infection, of whom 68% were discharged home, 29% were admitted to a regular floor, and 3% to an ICU. One thousand six hundred fifty-one of 3,369 patients tested have had SARS-CoV-2-positive results to date. Of patients with regular floor admissions, 13% were subsequently upgraded to the ICU after a median of 62 hours (interquartile range 28 to 106 hours). Fifty patients required invasive mechanical ventilation in the ED, 4 required out-of-hospital invasive mechanical ventilation, and another 167 subsequently required invasive mechanical ventilation in a median of 60 hours (interquartile range 26 to 99) hours after admission. Testing positive for SARS-CoV-2 and lower oxygen saturations were associated with need for ICU and invasive mechanical ventilation, and with death. High respiratory rates were associated with the need for ICU care. Conclusion: Persons under investigation for COVID-19 infection contribute significantly to the health care burden beyond those ruling in for SARS-CoV-2. For every 100 admitted persons under investigation, 9 will require ICU stay, invasive mechanical ventilation, or both on arrival and another 12 within 2 to 3 days of hospital admission, especially persons under investigation with lower oxygen saturations and positive SARS-CoV-2 swab results. This information should help hospitals manage the pandemic efficiently.

Team Triage Intervention, Including Licensed Practical Nurse, to Increase HIV Testing Rates in the Emergency Department: A Quality Improvement Project.

INTRODUCTION: Emergency departments have an important role in screening for human immunodeficiency virus infection and reducing the morbidity, mortality, and transmission of the human immunodeficiency virus. There are debates about human immunodeficiency virus screening, including opt-in, opt-out, and active choice models. Previous studies have shown that multiple factors affect the patient rate of acceptance, including where, when, and by whom the screening is offered. The purpose of this quality improvement project was to test a team-based triage intervention to improve the amount of HIV testing done in our emergency department. METHODS: The design was a single site quality improvement intervention with post-intervention monthly rates compared to historic monthly rate controls. The intervention focused on the introduction of a Licensed Practical Nurse in addition to the current triage process and personnel. The percentage of patients receiving human immunodeficiency virus testing and the number of tests sent per month before and after the implementation of the intervention were measured. RESULTS: Our results show that 0.6% (SD < 0.01) and 2.5% (SD 2.2) of patients received human immunodeficiency virus testing before and after implementation of the intervention, respectively (χ2 = 501.76, P < 0.05). A mean of 37.4 (SD = 12.91) and 151.3 (SD = 33.34) human immunodeficiency virus tests were sent per month before and after implementation of the intervention, respectively (t = 8.53, P < 0.001). DISCUSSION: This process intervention, in which licensed practical nurses offered human immunodeficiency virus screening tests during team triage, resulted in a 3-fold increase in the percentage of patients being tested for human immunodeficiency virus.

A Physician Nurse Team Adjacent to Triage Improves Length of Stay and Decreases Left Without Being Seen.

Introduction: Staffing significantly influences ED throughput, however there is a shortage of Registered Nurses (RNs), impacting ED flow and crowding. Non-RN providers, like Licensed Practical Nurses (LPNs), could potentially assist with tasks traditionally assigned to RNs. To improve the front-end ED process, we implemented an Attending Physician-Licensed Practical Nurse Team (PNT) positioned next to triage and utilized existing ED hallway space. Methods: This study took place at a tertiary care ED with over 110,000 annual visits. We compared postintervention (Post-PNT) data (11/1/22-2/28/23) to pre-intervention (Pre-PNT) data (7/31/22-10/31/22). The PNT, positioned adjacent to triage, expedited care for ED patients awaiting open rooms. They selected patients from the waiting room to bypass the Main ED, evaluated them in a private room, and then moved them to the hallway pending further care. Multivariable Regression Analysis was utilized to measure the impact of different factors on ED Length of Stay (LOS). Results: We analyzed 23516 patient visits, 10288 in the Pre-PNT period and 13288 in the Post-PNT period. Post-PNT consisted of 2454 PNT visits and 10834 non-PNT visits. The intervention led to significant improvements, including a decrease in mean ED LOS from 492 to 425 minutes, decrease in 72-hour revisits from 5.1% to 4.0%, decrease in Left Without Being Seen from 6.7% to 3.3%, and decrease in mean Arrival-to-Provider time from 74 minutes to 60 minutes. Multivariable Regression Analysis showed that ED LOS was significantly lower for Post-PNT patients than Pre-PNT. Conclusion: By leveraging the scope of LPNs and utilizing existing ED space, the PNT model successfully reduced front-end bottlenecks, leading to improved throughput, revisit rate, and LWBS rate.

The first gladius-bearing coleoid cephalopods from the lower Toarcian "Schistes Cartons" Formation of the Causses Basin (southeastern France).

The fossil record of gladius-bearing coleoids is scarce and based only on a few localities with geological horizons particularly favourable to their preservation (the so-called Konservat-Lagerstätten), which naturally leads to strongly limited data on geographical distributions. This emphasizes the importance of every new locality providing gladius-bearing coleoids. Here, we assess for the first time the gladius-bearing coleoid taxonomic diversity within the lower Toarcian "Schistes Cartons" of the Causses Basin (southeastern France). The material includes two fragmentary gladii, identified as Paraplesioteuthis sagittata and ?Loligosepia sp. indet. Just with these two specimens, two (Prototeuthina and Loligosepiina) of the three (Prototeuthina, Loligosepiina and Teudopseina) suborders of Mesozoic gladius-bearing coleoids are represented. Thus, our results hint at a rich early Toarcian gladius-bearing coleoid diversity in the Causses Basin and point out the need for further field investigations in the lower Toarcian "Schistes Cartons" in this area. This new record of Paraplesioteuthis sagittata is only the second one in Europe and the third in the world (western Canada, Germany and now France). Based on these occurrences, we tentatively suggest that P. sagittata originated in the Mediterranean domain and moved to the Arctic realm through the Viking Corridor to eventually move even farther to North America.

'Arm brains' (axial nerves) of Jurassic coleoids and the evolution of coleoid neuroanatomy.

Although patchy, the fossil record of coleoids bears a wealth of information on their soft part anatomy. Here, we describe remains of the axial nerve cord from both decabrachian (Acanthoteuthis, Belemnotheutis, Chondroteuthis) and octobrachian (Plesioteuthis, Proteroctopus, Vampyronassa) coleoids from the Jurassic. We discuss some hypotheses reflecting on possible evolutionary drivers behind the neuroanatomical differentiation of the coleoid arm crown. We also propose some hypotheses on potential links between habitat depth, mode of life and the evolution of the Coleoidea. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-023-00285-3.

Licensed Practical Nurses in Team Triage: A Safe Way to Address Nursing Shortages in the Emergency Department.

Background There is a Registered Nurse (RN) shortage across the United States that is predicted to intensify in the upcoming years. RNs are an integral part of Emergency Departments (EDs) and perform many vital tasks, including IV placement, blood draws, medication administration, acute assessments, and patient hand-offs. Thus, RN staffing is a crucial part of ED operations, and ED initiatives should account for RN workforce shortages. Given the increase in ED visits and crowding, throughput initiatives that can expedite patient care are integral to the functioning of an ED. Team Triage is a throughput initiative that has been shown to improve ED time to provider, length of stay, and left without being seen rates. In our institution, we created a Team Triage model where advanced practice providers (APPs) perform a patient's initial evaluation in triage and place orders for labs, intravenous (IV) catheters, and imaging. Given the RN staffing shortage, we incorporated Licensed Practical Nurses (LPNs) in Team Triage to place IV catheters and draw blood work for laboratory tests. The objective of this investigation was to describe a Team Triage model that incorporated LPNs and to report the patient safety and productivity of this model. Methods This was a single-site retrospective study at a large, academic, tertiary care center with over 100,000 annual visits. Adult patients who self-presented to the ED and went through Team Triage (11 am-11 pm) between Jan 1, 2020, and Jan 31, 2020, were included in this study. LPNs staffed the Team Triage, along with APPs. LPNs placed IV catheters and drew blood specimens for the Team Triage patients. The primary outcomes studied were the proportion of specimens mislabeled by LPNs, the proportion of patients receiving IV catheters, the proportion of patients receiving blood work, blood tubes drawn per hour, and IVs inserted per hour in Team Triage. Results During the study period, 1355 patients went through Team Triage. Of these patients, 1075 (79%) were ordered for blood work, and 1017 (75%) were ordered for an IV catheter. All Team Triage blood work and IV catheter placements were completed by LPNs, who staffed 372 hours of Team Triage. A total of 2558 blood tubes were collected by LPNs. The LPNs cared for 2.9 patients per hour, collected 6.9 blood tubes per hour, inserted 2.7 IV catheters per hour, and collected 2.4 blood tubes per patient. The LPNs had a 0% specimen mislabeling rate. Conclusion Due to the significant RN workforce shortage impacting Emergency Medicine coupled with increased ED crowding, there is a significant need to evaluate the integration of LPNs into Team Triage to place IV catheters and perform blood draws. This study shows that incorporating LPNs in Team Triage is a productive and safe way to address nursing shortages in Emergency Medicine.

Exceptional soft-tissue preservation of Jurassic Vampyronassa rhodanica provides new insights on the evolution and palaeoecology of vampyroteuthids.

Although soft tissues of coleoid cephalopods record key evolutionary adaptations, they are rarely preserved in the fossil record. This prevents meaningful comparative analyses between extant and fossil forms, as well as the development of a relative timescale for morphological innovations. However, unique 3-D soft tissue preservation of Vampyronassa rhodanica (Vampyromorpha) from the Jurassic Lagerstätte of La Voulte-sur-Rhône (Ardèche, France) provides unparalleled opportunities for the observation of these tissues in the oldest likely relative of extant Vampyroteuthis infernalis. Synchrotron X-ray microtomography and reconstruction of V. rhodanica allowed, for the first time, a high-resolution re-examination of external and internal morphology, and comparison with other fossil and extant species, including V. infernalis. The new data obtained demonstrate that some key V. infernalis characters, such as its unique type of sucker attachment, were already present in Jurassic taxa. Nonetheless, compared with the extant form, which is considered to be an opportunistic detritivore and zooplanktivore, many characters in V. rhodanica indicate a pelagic predatory lifestyle. The contrast in trophic niches between the two taxa is consistent with the hypothesis that these forms diversified in continental shelf environments prior to the appearance of adaptations in the Oligocene leading to their modern deep-sea mode of life.

Team triage increases discharges and decreases time to discharge without increasing test ordering.

OBJECTIVES: Emergency department (ED) crowding is detrimental to patients and staff. During traditional triage, nurses evaluate patients and identify their level of emergency. During team triage, physicians and/or nurse practitioners (NPs) and physician assistants (PAs) place orders, laboratory results, intravenous lines (IVs), and imaging in triage. Team triage improves access to testing and decreases length of stay. However, ordering practices in team triage may lead to overtesting. METHODS: This is a retrospective review of patients seen before and after a team triage process was established. Percentage of patients receiving testing and the diagnostic yields of troponins, lactates, international normalized ratios (INRs), blood cultures, glomerular filtration rates (GFR), and head computed tomography (CT) images were studied. RESULTS: A total of 704 traditionally triaged patients and 862 team triaged patients met inclusion criteria. Comparing traditional versus team triaged patients, the proportion of patients discharged was 0.44 versus 0.53 (P < 0.001), and the length of stay to discharge was 417 versus 375 minutes (P = 0.003). Comparing traditional versus team triage, a head CT was obtained 12.5% versus 5.7% (P < 0.001) of the time with diagnostic yield 45.5% versus 52% (not significant), troponin was obtained 51.3% versus 45.9% (not significant) of the time with diagnostic yield 14.9% versus 13.9% (not significant), lactate was obtained 41.6% versus 32.1% (P = 0.011) of the time with diagnostic yield 18.4% versus 12.3% (not significant), INR was obtained 70.2% versus 55.8% (P = 0.007) of the time with diagnostic yield 15.8% versus 10.5% (P = 0. 042), GFR was obtained 99.3% versus 98.4% (not significant) of the time with diagnostic yield 18.9% versus 13.7% (P = 0.02), and blood cultures were obtained 23.4% versus 7.3% (P < 0.001) of the time with diagnostic yield 7.3% versus 9.3% (not significant). CONCLUSION: Compared with traditional triage, the team triage process increased discharges and decreased time to discharge, but did not lead to increased testing or decreased diagnostic yield.

Characterization of wise protein and its molecular mechanism to interact with both Wnt and BMP signals.

Cross-talk of BMP and Wnt signaling pathways has been implicated in many aspects of biological events during embryogenesis and in adulthood. A secreted protein Wise and its orthologs (Sostdc1, USAG-1, and Ectodin) have been shown to modulate Wnt signaling and also inhibit BMP signals. Modulation of Wnt signaling activity by Wise is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands. Here we have investigated the mode of action of Wise on Wnt and BMP signals. It was found that Wise binds LRP6 through one of three loops formed by the cystine knot. The Wise deletion construct lacking the LRP6-interacting loop domain nevertheless binds BMP4 and inhibits BMP signals. Moreover, BMP4 does not interfere with Wise-LRP6 binding, suggesting separate domains for the physical interaction. Functional assays also show that the ability of Wise to block Wnt1 activity through LRP6 is not impeded by BMP4. In contrast, the ability of Wise to inhibit BMP4 is prevented by additional LRP6, implying a preference of Wise in binding LRP6 over BMP4. In addition to the interaction of Wise with BMP4 and LRP6, the molecular characteristics of Wise, such as glycosylation and association with heparan sulfate proteoglycans on the cell surface, are suggested. This study helps to understand the multiple functions of Wise at the molecular level and suggests a possible role for Wise in balancing Wnt and BMP signals.

Wise, a context-dependent activator and inhibitor of Wnt signalling.

We have isolated a novel secreted molecule, Wise, by a functional screen for activities that alter the anteroposterior character of neuralised Xenopus animal caps. Wise encodes a secreted protein capable of inducing posterior neural markers at a distance. Phenotypes arising from ectopic expression or depletion of Wise resemble those obtained when Wnt signalling is altered. In animal cap assays, posterior neural markers can be induced by Wnt family members, and induction of these markers by Wise requires components of the canonical Wnt pathway. This indicates that in this context Wise activates the Wnt signalling cascade by mimicking some of the effects of Wnt ligands. Activation of the pathway was further confirmed by nuclear accumulation of beta-catenin driven by Wise. By contrast, in an assay for secondary axis induction, extracellularly Wise antagonises the axis-inducing ability of Wnt8. Thus, Wise can activate or inhibit Wnt signalling in a context-dependent manner. The Wise protein physically interacts with the Wnt co-receptor, lipoprotein receptor-related protein 6 (LRP6), and is able to compete with Wnt8 for binding to LRP6. These activities of Wise provide a new mechanism for integrating inputs through the Wnt coreceptor complex to modulate the balance of Wnt signalling.