Critical Steps for Determining Capacity to Refuse Emergency Medical Services Transport: A Modified Delphi Study.

OBJECTIVES: Emergency physicians without specialized Emergency Medical Services (EMS) training are often required to provide online medical oversight. One common ethical question faced by these physicians is the assessment for decision-making capacity in a patient who does not accept EMS transport to the hospital. We sought expert consensus for a standardized set of guiding questions and recommendations to ensure a rigorous and feasible capacity assessment. METHODS: A modified Delphi method approach was used to achieve group consensus among expert individuals. Nineteen physician experts were recruited from across the country, representing populations totaling over 22 million and a variety of urban, suburban, and rural practice environments. Experts completed a Round 1 survey that included 19 questions surrounding best practices for capacity evaluation among patients refusing transport. The threshold for consensus was predefined as 80% agreement. Participants gathered virtually meeting where the results from the first round were shared with the group. Discussion generated new items and refined the language of existing items. Following the virtual meeting, a Round 2 survey was conducted, and voted on by the panel for the items that did not meet consensus in Round 1. RESULTS: After the first round, 15 of 19 items reached consensus. Three of the items that met consensus were universally noted to require language modification for clarification. A large portion of the discussion involved the proper method of integrating patient concerns around ambulance transport (e.g., cost of transport, financial concerns, social barriers) into the capacity assessment and whether alternate care options should be discussed. After the second round of voting, one additional item was reversed to meet consensus, resulting in a total of 16 items. CONCLUSIONS: A consensus expert panel was able to agree upon 16 standardized steps to guide best practices and assist emergency physicians in real-time evaluation of patients that refuse EMS transport.

Mapping of susceptibility loci for Ebola virus pathogenesis in mice.

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.

3D printing of heart valves.

3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.

Engineering Heart Valve Interfaces Using Melt Electrowriting: Biomimetic Design Strategies from Multi-Modal Imaging.

Interfaces within biological tissues not only connect different regions but also contribute to the overall functionality of the tissue. This is especially true in the case of the aortic heart valve. Here, melt electrowriting (MEW) is used to engineer complex, user-defined, interfaces for heart valve scaffolds. First, a multi-modal imaging investigation into the interfacial regions of the valve reveals differences in collagen orientation, density, and recruitment in previously unexplored regions including the commissure and inter-leaflet triangle. Overlapping, suturing, and continuous printing methods for interfacing MEW scaffolds are then investigated for their morphological, tensile, and flexural properties, demonstrating the superior performance of continuous interfaces. G-codes for MEW scaffolds with complex interfaces are designed and generated using a novel software and graphical user interface. Finally, a singular MEW scaffold for the interfacial region of the aortic heart valve is presented incorporating continuous interfaces, gradient porosities, variable layer numbers across regions, and tailored fiber orientations inspired by the collagen distribution and orientation from the multi-modal imaging study. The scaffold exhibits similar yield strain, hysteresis, and relaxation behavior to porcine heart valves. This work demonstrates the ability of a bioinspired approach for MEW scaffold design to address the functional complexity of biological tissues.