NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and ...maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here, we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs shows that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is required to maintain MYC expression in NMC cell lines. Moreover, both siRNA knockdown of MYC and a dominant-negative form of MYC, omomyc, induce differentiation of NMC cells. Conversely, differentiation of NMC cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of MYC. Together, these findings suggest that MYC is a downstream target of BRD4-NUT that is required for maintenance of NMC cells in an undifferentiated, proliferative state. Our findings support a model in which dysregulation of MYC by BRD-NUT fusion proteins has a central role in the pathogenesis of NMC.
The prevalence of agitation among emergency department (ED) patients is increasing. Physical restraints are routinely used to prevent self-harm and to protect staff, but are associated with serious ...safety risks. To date, characterization of physical restraint use in the emergency setting has been limited. We thus aim to describe restraint patterns in the general ED to guide future investigation in the management of behavioral disorders.
We conducted a cross-sectional study of adult patients presenting to 5 adult EDs within a large regional health system for 2013 to 2015, and with a physical restraint order during their visit. We undertook descriptive analyses and cluster analysis to determine unique meaningful groups within our sample.
In 956,153 total ED visits, 4,661 patients (0.5%) had associated restraint orders, representing 3,739 unique patients. The median age was 47 years (interquartile range 32 to 59 years), 66.7% of patients were men, 61.9% had a psychiatric history, and 91.1% arrived by ambulance. For chief complaints, 33.7% were alcohol or drug use, 45.4% medical, 12.3% psychiatric, and 8.5% trauma. Cluster analysis identified 2 distinct cohorts. A younger, predominantly male population presented with alcohol or drug use, whereas an older group arrived with medical complaints.
Our data found strong association of alcohol or drug use with physical restraints and identified a unique elderly population with behavioral disturbances in the ED. Further characterization of causal links and safer practices to manage agitation for these vulnerable populations are needed.
In March 2020, the novel coronavirus 2019 (COVID-19) became a global pandemic. Medical schools around the United States faced difficult decisions, temporarily suspending hospital-based clerkship ...rotations for medical students due to potential shortages of personal protective equipment and a need to social distance. This decision created a need for innovative, virtual learning opportunities to support undergraduate medical education.
Educators at Yale School of Medicine developed a novel medical student curriculum converting high-fidelity, mannequin-based simulation into a fully online virtual telesimulation format. By using a virtual videoconferencing platform to deliver remote telesimulation as an immersive educational experience for widely dispersed students, this novel technology retains the experiential strengths of simulation-based learning while complying with needs for social distancing during the pandemic. The curriculum comprises simulated clinical scenarios that include live patient actors; facilitator interactions; and real-time assessment of vital signs, labs, and imaging. Each 90-minute session includes 2 sets of simulation scenarios and faculty-led teledebriefs. A team of 3 students performs the first scenario, while an additional team of 3 students observes. Teams reverse roles for the second scenario.
The 6-week virtual telesimulation elective enrolled the maximum 48 medical students and covered core clinical clerkship content areas. Communication patterns within the virtual telesimulation format required more deliberate turn-taking than normal conversation. Using the chat function within the videoconferencing platform allowed teams to complete simultaneous tasks. A nurse confederate provided cues not available in the virtual telesimulation format.
Rapid dissemination of this program, including online webinars and live demonstration sessions with student volunteers, supports the development of similar programs at other universities. Evaluation and process improvement efforts include planned qualitative evaluation of this new format to further understand and refine the learning experience. Future work is needed to evaluate clinical skill development in this educational modality.
Over 1.7 million episodes of agitation occur annually across the United States in emergency departments (EDs), some of which lead to workplace assaults on clinicians and require invasive methods like ...physical restraints to maintain staff and patient safety. Recent studies demonstrated that experiences of workplace violence contribute to symptoms of burnout, which may impact future decisions regarding use of physical restraints on agitated patients. To capture the dynamic interactions between clinicians and agitated patients under their care, we applied qualitative system dynamics methods to develop a model that describes feedback mechanisms of clinician burnout and the use of physical restraints to manage agitation.
We convened an interprofessional panel of clinician stakeholders and agitation experts for a series of model building sessions to develop the current model. The panel derived the final version of our model over ten sessions of iterative refinement and modification, each lasting approximately three to four hours. We incorporated findings from prior studies on agitation and burnout related to workplace violence, identifying interpersonal and psychological factors likely to influence our outcomes of interest to form the basis of our model.
The final model resulted in five main sets of feedback loops that describe key narratives regarding the relationship between clinician burnout and agitated patients becoming physically restrained: (1) use of restraints decreases agitation and risk of assault, leading to increased perceptions of safety and decreasing use of restraints in a balancing feedback loop which stabilizes the system; (2) clinician stress leads to a perception of decreased safety and lower threshold to restrain, causing more stress in a negatively reinforcing loop; (3) clinician burnout leads to a decreased perception of colleague support which leads to more burnout in a negatively reinforcing loop; (4) clinician burnout leads to negative perceptions of patient intent during agitation, thus lowering threshold to restrain and leading to higher task load, more likelihood of workplace assaults, and higher burnout in a negatively reinforcing loop; and (5) mutual trust between clinicians causes increased perceptions of safety and improved team control, leading to decreased clinician stress and further increased mutual trust in a positively reinforcing loop.
Our system dynamics approach led to the development of a robust qualitative model that illustrates a number of important feedback cycles that underly the relationships between clinician experiences of workplace violence, stress and burnout, and impact on decisions to physically restrain agitated patients. This work identifies potential opportunities at multiple targets to break negatively reinforcing cycles and support positive influences on safety for both clinicians and patients in the face of physical danger.
...managing patient agitation, defined as excessive psychomotor activity leading to aggressive and violent behavior, is a critical skill of physicians to help ensure the safety of patients and staff ...alike. In vivo moments of agitation management may also not be safe for early learners given the risk of physical injury. ...early clinical exposure to agitation management is often limited for medical students. By completing the survey, they agreed to participate in data collection. The response rate for those who completed both pre- and post-session surveys was 67% (n = 43).
Health system science (HSS) encompasses both core and cross-cutting domains that emphasize the complex interplay of care delivery, finances, teamwork, and clinical practice that impact care quality ...and safety in health care. Although HSS skills are required during residency training for physicians, current HSS didactics have less emphasis on hands-on practice and experiential learning. Medical simulation can allow for experiential participation and reflection in a controlled environment. Our goal was to develop and pilot three simulation scenarios as part of an educational module for resident physicians that incorporated core and cross-cutting HSS domains. METHODS: Each scenario included a brief didactic, an interactive simulation in small-group breakout rooms, and a structured debriefing. The case scenario topics consisted of educational leadership, quality and safety, and implementation science. Learners from four residency programs (psychiatry, emergency medicine, orthopedics, ophthalmology) participated January - March 2021.
A total of 95 resident physicians received our curricular module, and nearly all (95%) participants who completed a post-session survey reported perceived learning gains. Emotional reactions to the session were positive especially regarding the interactive role-play format. Recommendations for improvement included participation from non-physician professions and tailoring of scenarios for specific disciplines/role. Knowledge transfer included use of multiple stakeholder perspectives and effective negotiation by considering power/social structures.
The simulation-based scenarios can be feasibly applied for learner groups across different residency training programs. Simulations were conducted in a virtual learning environment, but future work can include in-person and actor-based simulations to further enhance emotional reactions and the reality of the case scenarios.
Physician assistants (PA) are an important part of emergency department healthcare delivery and are increasingly seeking specialty-specific postgraduate training. Our goal was to pilot the ...implementation of a PA postgraduate program within an existing physician residency program and produce emergency medicine-PA (EM-PA) graduates of comparable skill to their physician counterparts who have received the equivalent length of EM residency training to date (evaluated at the end of first year of EM training).The curriculum was based on the Society for Emergency Medicine Physician Assistants (SEMPA) recommendations with a special focus on side-by-side training with EM resident physicians. In reviewing the program, the authors examined faculty evaluations, as well as procedure and ultrasound experience that the trainees received. We found comparable evaluations between first-year EM-PA and physician trainee cohorts. This program serves as a pilot study to demonstrate the feasibility of collocating clinical and didactic programming for physicians and EM-PAs during their postgraduate training. This brief innovation report outlines the logistics of the clinical and didactic curriculum and provides a summary of outcomes evaluated.
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