Performance of the Medical Priority Dispatch System® in Identifying Patients Requiring Chest Compressions at Overdose Prevention Services: A Retrospective Cohort Study.

BACKGROUND AND AIMS: The Medical Priority Dispatch System (MPDS)® is used to triage 9-1-1 calls according to acuity, with certain coding receiving telecommunicator cardiopulmonary resuscitation (T-CPR) for suspected out-of-hospital cardiac arrest (OHCA). However, this may be challenging for those with drug poisoning emergencies, who may resemble OHCA. We sought to examine the performance of the system to correctly identify cases requiring T-CPR, specifically at overdose prevention services (OPS). METHODS: This retrospective cohort study included patients attended by the provincial emergency medical system (EMS) (May 1, 2019-January 31, 2023). We calculated the diagnostic performance of MPDS® assessment of whether the case required T-CPR instructions against the gold standard of whether the patient was found pulseless on EMS clinician arrival. We compared performance among subgroups, specifically OPS vs other locations and drug poisoning-classified cases vs other case classifications. RESULTS: Comparing OPS to other locations, the sensitivity of MPDS® was similar (66.7% vs 62.4%, p = 0.4), with lower specificity (87.3% vs 98.1%, p < 0.01) and positive predictive value (0.3% vs 35.7%, p < 0.01) and higher negative predictive value (99.9% vs 99.4%, p < 0.01). The negative likelihood ratio of MPDS® was 0.381 at OPS locations, compared with 0.383 at other locations, while the positive likelihood ratio was 5.24, compared with 32.36. In patients with drug poisoning emergencies, compared with other 9-1-1 events, MPDS® had higher sensitivity (83.6% vs 60.6%, p < 0.01) but lower specificity (77.6% vs 98.9%, p < 0.01) and positive predictive value (10.5% vs 48.5%, p < 0.01), and similar negative predictive value (99.33% vs 99.35%, p = 0.03). The negative likelihood ratio of MPDS® was 0.212 in drug poisoning emergencies compared with 0.398 for all other presentations, and the positive likelihood ratio was 3.73 compared with 57.88. DISCUSSION AND CONCLUSIONS: The ability of MPDS® to correctly identify patients needing telecommunicator cardiopulmonary resuscitation instructions differed between OPS settings and other locations, frequently recommending T-CPR for patients not suffering OHCA at an OPS. Different strategies developed in collaboration with people who use substances are required to better tailor dispatch instructions prior to EMS arrival to avoid delays in life-saving interventions.

The paramedic-general practitioner relationship: a scoping review.

BACKGROUND: Health services internationally are implementing programs that increase working ties between paramedics and general practitioners (GPs) to reduce unnecessary transport to emergency departments (EDs) and improve access to primary health care. As paramedic involvement in primary health care develops, there is increasing focus on the GP-paramedic collaborative relationship. Resulting issues regarding professional boundaries may occur, as paramedics practice in fields that were previously solely in the GP scope. An effective paramedic-GP working relationship will be an essential foundation to the success of future strategies. METHODS: A search of three electronic databases was completed (Ovid MEDLINE, Embase Classic+ Embase and CINAHL Plus). Eligibility for inclusion required analysis of the relationship between paramedics and GPs. All processes were completed by two independent reviewers. RESULTS: After removal of duplicates, 4995 titles were screened by title and/or abstract. After full-text review, 15 studies were included. Five themes were identified that contribute significantly to the strengths and weaknesses of the relationship - the importance of communication, understanding scope of practice, leadership roles, responsibility for patient care and interdisciplinary training. Issues identified included significant variation in the structure of different emergency medical services and varying standards of education requirements for paramedics worldwide. CONCLUSIONS: There were no published Australian studies that had the primary aim of examining the paramedic-GP relationship. The depth of research on this topic is lacking, despite increased interest over the past decade. The relevance of the international literature to the Australian setting is questionable.

Strengths and challenges with spiritual care: Student feedback from the EPICC Spiritual Care Self-Assessment Tool.

AIM: To explore qualitative data from students' self-reported competencies in spiritual care gathered during testing of a student self-assessment tool based on the EPICC Spiritual Care Education Standard. DESIGN: Reflexive thematic analysis of qualitative data from a multinational study on validating a new self-assessment tool. METHODS: The EPICC Spiritual Care Education Standard for competency in spiritual care was developed to enhance nurses' and midwives' ability to provide spiritual care by creating a baccalaureate education standard for spiritual care competencies. Spiritual care researchers then developed a self-assessment tool to raise student awareness of spirituality and track personal and professional growth in spiritual care competency. The EPICC Spiritual Care Competency Self-Assessment Tool, tested at eight universities in five countries, provided many opportunities for student comments, resulting in rich qualitative data presented here. RESULTS: Themes related to strengths, weaknesses and areas for improvement. Identified strengths were similar across countries: caring attitudes, general knowledge of caring and compassion and good communication skills. Weaknesses/challenges touched on spirituality as overlooked in some cultures but part of life for others, complex questions were hard to understand, and self-assessment tools are common for some and rare for others. Areas for improvement included need for knowledge of religious and other deeply held beliefs and for greater spiritual assessment skills. Similarities across countries related to basic training in communication and compassionate care for nurses globally. Differences lay in the challenges and/or barriers for spiritual care and may relate to cultures within countries and/or university test sites. RELEVANCE TO CLINICAL PRACTICE: The Tool raises awareness of spirituality among students and working nurses, providing an accessible way to self-check personal and professional growth in spiritual care competencies, which increases student and nurse capacity to become more knowledgeable and skilled in facilitating spiritual care, thus be role models for students at the intersection of spirituality and health.

Interprofessional peer assisted learning: Paramedic students learning falls assessments from Occupational Therapy students.

Peer-assisted learning (PAL) describes a program in which students learn from students from the same health discipline. This teaching method has gained significant momentum over the past decade as an effective learning strategy for undergraduate healthcare students. Paramedic programs are increasingly utilizing PAL, however there is a scarcity of literature about interprofessional PAL, particularly between Paramedics and allied health students. This project was an evaluation of a pilot educational intervention involving final year undergraduate paramedic students. Occupational Therapy (OT) peer instructors facilitated a session on falls' risk assessments during a scheduled undergraduate Paramedic practical class. The OT peer instructors discussed pertinent considerations for Paramedics attending to elderly patients who have fallen, and then provided direct feedback to the Paramedic students during a case simulation. At the conclusion of the session, Paramedic students completed a survey evaluating their reaction to and learning from the teaching session. Results indicated that interprofessional PAL can improve undergraduate paramedic students' knowledge and confidence in performing a new skill that is well understood by another allied health profession. This adds to the body of empirical research on interprofessional PAL and supports its inclusion as a teaching modality into undergraduate healthcare programs such as Paramedicine.

No Two Systems Are the Same: Paramedic Perceptions of Contemporary System Performance Using Prehospital Quality Indicators.

Introduction In recent years, researchers have identified two new models of paramedicine within the Anglo-American paramedic system known as the Directive and Professionally Autonomous paramedic systems. The research team now seek to compare paramedic perception of system performance between the two systems using prehospital quality indicators. Methods Paramedics employed within Anglo-American paramedic systems undertook a survey evaluating their experience and perception of system performance against a set of modified prehospital quality indicators. Data were collected using a survey combining single-choice questions with matrix multiple-choice questions. Key results were cross-tabulated with demographic (informant) and system factors to compare performance between the two new paramedic systems. Results The survey indicated a substantial difference in perceived clinical and operational performance between the Professionally Autonomous and Directive paramedic systems, with the Professionally Autonomous paramedic system performing consistently better in all 11 prehospital quality indicator domains. Conclusion The results of this survey are a vital step in helping paramedics, health leaders, and academics understand the complex relationship between paramedic system design and system performance, and, for the first time, provides empirical evidence upon which to make a conscious decision to adopt one system or the other.

Shaping the future design of paramedicine: A knowledge to action framework to support paramedic system modernization.

BACKGROUND: Over the past two decades, the demands placed on modern paramedic systems has changed. Paramedic services can no longer continue to operate on a traditional response model where more ambulances are deployed to meet the rising demand of patients calling for their health needs. Recent research has explored system design in paramedicine and its relationship with organizational performance. Two subsequent paramedic systems have been identified with one, the Professionally Autonomous paramedic system, being linked to higher performance. Yet, how to operationalize this model for system modernization continues to be a gap in practice. OBJECTIVE: To provide health leaders and policy makers with a framework from which to drive paramedic system modernization. METHODS: This study uses the Knowledge to Action framework to develop an implementation plan for systems that seek to modernize their service delivery model toward that of a Professionally Autonomous paramedic system. RESULTS: A detailed plan of the steps required to undertake system transformation are outlined. Whilst this framework outlines the components required for system modernization, it does not propose an in-depth outline of each of the steps required to achieve each component. Rather, end users are encouraged to develop individual implementation plans tailored to the local context using the comprehensive tools outlined within. CONCLUSION: This knowledge to action framework provides health leaders and policy makers with a uniform roadmap for paramedic system modernization intended to improve health (clinical) outcomes as well as health system outcomes through the Professional Autonomous paramedicine model.

Clinical reasoning in undergraduate paramedicine: utilisation of a script concordance test.

INTRODUCTION: Clinical reasoning is a complex cognitive and metacognitive process paramount to patient care in paramedic practice. While universally recognised as an essential component of practice, clinical reasoning has been historically difficult to assess in health care professions. Is the Script Concordance Test (SCT) an achievable and reliable option to test clinical reasoning in undergraduate paramedic students? METHODS: This was a single institution observational cohort study designed to use the SCT to measure clinical reasoning in paramedic students. Clinical vignettes were constructed across a range of concepts with varying shades of clinical ambiguity. A reference panel mean scores of the test were compared to that of students. Test responses were graded with the aggregate scoring method with scores awarded for both partially and fully correct responses. RESULTS: Eighty-three student paramedic participants (mean age: 21.8 (3.5) years, 54 (65%) female, 27 (33%) male and 2 (2%) non-binary) completed the SCT. The difference between the reference group mean score of 80 (5) and student mean of score of 65.6 (8.4) was statistically significant (p < 0.001). DISCUSSION: Clinical reasoning skills are not easily acquired as they are a culmination of education, experience and the ability to apply this in the context to a specific patient. The SCT has shown to be reliable and effective in measuring clinical reasoning in undergraduate paramedics as it has in other health professions such as nursing and medicine. More investigation is required to establish effective pedogeological techniques to optimise clinical reasoning in student and novice paramedics who are devoid of experience.

A conceptual framework for the exploration of the relationship between systems of paramedicine and system performance.

BACKGROUND: Over the past 60 years since its inception, the Anglo-American Paramedic System has continued to grow and evolve. While brief and fragmented accounts of the differences between systems have been noted in the literature, until recently there has been a paucity of research that explores and identifies sub-models of paramedicine within the Anglo-American Paramedic System. OBJECTIVES: This article describes a conceptual framework that sets a roadmap for defining and comparing two newly identified sub-models of the Anglo-American Paramedic System. METHODS: A conceptual framework for the exploration of these novel sub-models was developed on the basis of the work completed by Donabedian as well as Turncock and Handler. These two sub-models worked to develop a model for quality assessment and performance measurement in the public health system. RESULTS: The conceptual framework consists of six components that are strongly related to each other: system design, macro context, mission and purpose, structure, service delivery models and quality outcome measures. While this framework relates specifically to two novel paramedic systems known as the Professionally Autonomous an Directive paramedic systems, it can be used to measure any integrated health model. CONCLUSION: The conceptual framework described in this paper provides a stepwise roadmap for the definition and comparison of the newly identified paramedic systems to better inform future research that defines and compares paramedic system design and performance.

Developing and testing the EPICC Spiritual Care Competency Self-Assessment Tool for student nurses and midwives.

AIMS AND OBJECTIVES: To develop and psychometrically test a self-assessment tool that measures undergraduate nursing and midwifery students' perceptions of spiritual care competence in health care practice. BACKGROUND: Spiritual care is part of nurses/midwives' responsibility. There is a need to better benchmark students' competency development in spiritual care through their education. The EPICC Spiritual Care Education Standard served as groundwork for the development of the EPICC Spiritual Care Competency Self-Assessment Tool. DESIGN: Cross sectional, mixed methods design. A STROBE checklist was used. METHODS: The Tool (available in English, Dutch and Norwegian) was developed by an international group. It was tested between July-October 2020 with a convenience sample of 323 nursing/midwifery students at eight universities in five countries. The Tool was tested for validity using Kaiser-Meyer-Olkin (KMO) test, exploratory and confirmatory factor analysis, one-way ANOVA and independent samples t test. The reliability was tested by Cronbach's alpha coefficient. Qualitative data were analysed using thematic analysis. RESULTS: The KMO test for sampling adequacy was 0.90. All, but two, items were related to the same factor. Cronbach's alpha coefficient for the Tool was 0.91. Students found the Tool easy to use, and they gained new insights by completing it. However, students felt that some questions were repetitive and took time to complete. CONCLUSIONS: The Tool has construct and discriminant validity, and high internal consistency (is reliable). In addition, students found the Tool useful, especially in early stages of education. RELEVANCE TO CLINICAL PRACTICE: The Tool affords student nurses and midwives the opportunity to self-evaluate their knowledge, skills and attitudes about spirituality and spiritual care. The Tool offers students, educators and preceptors in clinical practice a tangible way of discussing and evaluating spiritual care competency.

Identification of an Epi-metabolic dependency on EHMT2/G9a in T-cell acute lymphoblastic leukemia.

Genomic studies have identified recurrent somatic alterations in genes involved in DNA methylation and post-translational histone modifications in acute lymphoblastic leukemia (ALL), suggesting new opportunities for therapeutic interventions. In this study, we identified G9a/EHMT2 as a potential target in T-ALL through the intersection of epigenome-centered shRNA and chemical screens. We subsequently validated G9a with low-throughput CRISPR-Cas9-based studies targeting the catalytic G9a SET-domain and the testing of G9a chemical inhibitors in vitro, 3D, and in vivo T-ALL models. Mechanistically we determined that G9a repression promotes lysosomal biogenesis and autophagic degradation associated with the suppression of sestrin2 (SESN2) and inhibition of glycogen synthase kinase-3 (GSK-3), suggesting that in T-ALL glycolytic dependent pathways are at least in part under epigenetic control. Thus, targeting G9a represents a strategy to exhaust the metabolic requirement of T-ALL cells.

From stretcher bearer to practitioner: A brief narrative review of the history of the Anglo-American paramedic system.

BACKGROUND: This narrative review presents a brief chronological history of the Anglo-American paramedic system, combining decades of stories from across ambulance services in western, English-speaking developed countries METHODS: Databases, including Embase, MEDLINE, Web of Science, CINAHL and Google Scholar were searched from the inception of the databases. A grey literature search strategy was conducted to identify non-indexed relevant literature along with forwards and backwards searching of citations and references of included studies. Two reviewers undertook title and abstract screening, followed by full-text screening. Included studies were summarised using narrative synthesis structured around the exploration of the history of the Anglo-American paramedic system. RESULTS: The research team structured the narrative in chronological order and used metaphorical models based on philosophical underpinnings to describe in detail each era of paramedicine. The narrative explores several key milestones including, industrial orientation, scope of practice, innovation, education and training, regulation as well as significant clinical and technological advancements in the delivery of traditional and non-traditional paramedic care to patients. CONCLUSIONS: Paramedicine, like other allied health professions, has successfully navigated the pathway toward professionalisation in a considerably short period of time. From its noble beginnings as stretcher bearers in times of war, the profession has looked outwards to emulate the success of our healthcare colleagues in establishing its own unique body of knowledge supported by strong clinical governance, national registration, professional regulatory boards, self-regulation, and a move towards higher education supported by the development of entry-to-practice degrees. Whilst the profession has achieved many great milestones, their application across multiple jurisdictions within the Anglo-American paramedic system remains inconsistent, and more research is needed to explore why this is.

Development of a spiritual care education matrix: Factors facilitating/hindering improvement of spiritual care competency in student nurses and midwives.

Spiritual care is a fundamental aspect of caring and compassionate nursing/midwifery practice. However, nurses/midwives consistently report feeling unprepared to provide spiritual care for various reasons. A key reason appears to be the lack of structured spiritual care education in undergraduate nursing/midwifery curricula. Between 2016 and 2019, the three-year, European EPICC project ('Enhancing nurses' and midwives' competence in Providing spiritual care through Innovative education and 'Compassionate Care') sought to address gaps in nursing/midwifery competence in spiritual care. A key project output, and the focus of this paper, is the EPICC Gold Standard Matrix for Spiritual Care Education ('EPICC Matrix'), which depicts the complex array of factors hindering/facilitating the development of nursing/midwifery spiritual care competency. The EPICC project followed two major studies that identified factors contributing to nursing/midwifery spiritual care competency development. This evidence, along with the mixed methods focus of the EPICC project to enable co-projection of its outputs informed the development of the EPICC Matrix. The EPICC Matrix was considered to represent 'the cultural, social and political environment in which spiritual care competency develops' in student nurses/midwives. The EPICC Matrix illustrates spiritual care educational considerations during the process of selecting suitable nursing/midwifery students; through the specific aspects of the teaching and learning environment, the student as a person, and the clinical environment in which spiritual care competency develops; and finally, how the student is assessed as competent in providing spiritual care. Recent research supports the use of the EPICC Matrix in undergraduate nursing/midwifery curricula and strengthens the case for support of the other EPICC project outputs, including: the EPICC Spiritual Care Education Standard, EPICC Adoption Toolkit, and the continuation of the EPICC Network. Further testing of the EPICC Matrix to determine its relevance in different cultural/professional contexts within and outside of Europe would be welcomed.

Acute Kidney Injury in Dogs and Cats.

Acute kidney injury can cause significant morbidity and mortality in dogs and cats. Knowledge of the pathophysiology of renal damage can be beneficial to prevention and treatment. There are many causes of acute kidney injury, and the prognosis for each can vary. Appropriate fluid therapy and monitoring are essential for treatment.

Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts.

Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells implicated in inflammatory pathways. We identified the immune modulator IRF2BP2 as a selective AML dependency. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene-expression studies demonstrated that IRF2BP2 represses IL1ß/TNFα signaling via NFκB, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival. SIGNIFICANCE: This study exploits inflammatory programs inherent to AML blasts to identify genetic vulnerabilities in this disease. In doing so, we determined that AML cells are dependent on the transcriptional repressive activity of IRF2BP2 for their survival, revealing cell-intrinsic inflammation as a mechanism priming leukemic blasts for regulated cell death. See related commentary by Puissant and Medyouf, p. 1617. This article is highlighted in the In This Issue feature, p. 1599.

Out-of-hospital or pre-hospital: Is it time to reconsider the language used to describe and define paramedicine?

The professionalisation of paramedicine in Australasia necessitates discussion about how the profession defines and describes itself in the literature and more broadly. This editorial discusses the descriptors pre-hospital care and out-of-hospital care, and the connotations, relevance and implications of their use to describe paramedic roles and practice.

Educational interventions and strategies for spiritual care in nursing and healthcare students and staff: A scoping review.

AIMS AND OBJECTIVES: To map existing evidence about educational interventions or strategies in nursing and allied healthcare concerning students' and staffs' spiritual care provision. BACKGROUND: Spiritual care is an important part of whole person care, but healthcare staff lack competence and awareness of spiritual issues in practice. To rectify this, it is important to identify what educational approaches are most helpful in supporting them to provide spiritual care. DESIGN: A scoping review using the PRISMA-ScR checklist. METHOD: Searches in the databases CINAHL, MEDLINE, ATLA and ERIC were conducted for papers spanning January 2009-May 2020. Search terms were related to spirituality, spiritual care, education and clinical teaching. Appraisal tools were used. RESULTS: From the 2128 potentially relevant papers, 36 were included. The studies were from 15 different countries and involved nurses, physicians and other health-related professions, and both quantitative, qualitative and mixed methods were used. The results are presented in three themes: Understanding of spirituality, Strategies in educational settings, and Strategies in practice settings. The review points to great diversity in the content, lengths and setting of the educational interventions or strategies. CONCLUSIONS: Courses in spiritual care should be implemented in curricula in both undergraduate and postgraduate education, and several studies suggest it should be mandatory. Courses should also be available for healthcare staff to raise awareness and to encourage the integration of spiritual care into their everyday practice. There is a need for greater consensus about how spirituality and spiritual care are described in healthcare settings. RELEVANCE TO CLINICAL PRACTICE: Spiritual care must be included both in monodisciplinary and multidisciplinary educational settings. The main result of spiritual care courses is in building awareness of spiritual issues and self-awareness. To ensure the provision of spiritual care for patients in healthcare practices, continuing and multidisciplinary education is recommended.

Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy.

Despite progress in the treatment of acute lymphoblastic leukemia (ALL), T-cell ALL (T-ALL) has limited treatment options, particularly in the setting of relapsed/refractory disease. Using an unbiased genome-scale CRISPR-Cas9 screen we sought to identify pathway dependencies for T-ALL which could be harnessed for therapy development. Disruption of the one-carbon folate, purine and pyrimidine pathways scored as the top metabolic pathways required for T-ALL proliferation. We used a recently developed inhibitor of SHMT1 and SHMT2, RZ-2994, to characterize the effect of inhibiting these enzymes of the one-carbon folate pathway in T-ALL and found that T-ALL cell lines were differentially sensitive to RZ-2994, with the drug inducing a S/G2 cell cycle arrest. The effects of SHMT1/2 inhibition were rescued by formate supplementation. Loss of both SHMT1 and SHMT2 was necessary for impaired growth and cell cycle arrest, with suppression of both SHMT1 and SHMT2 inhibiting leukemia progression in vivo. RZ-2994 also decreased leukemia burden in vivo and remained effective in the setting of methotrexate resistance in vitro. This study highlights the significance of the one-carbon folate pathway in T-ALL and supports further development of SHMT inhibitors for treatment of T-ALL and other cancers.

Defining two novel sub models of the Anglo-American paramedic system: A Delphi study.

INTRODUCTION: While brief and fragmented accounts of the differences between systems have been noted in the literature, until recently there has been a lack of research that explores and identifies new sub-models of paramedicine within the Anglo-American paramedic system. METHODS: A Delphi method was used to gain consensus among international paramedic experts regarding two new models of paramedicine known as the Directive and Professionally Autonomous paramedic systems. Following the development of a preliminary definition, a set of questions were established for experts aimed at defining the new sub-models; the responses were reviewed and amended based on feedback before being re-distributed to an expanded group of participants for further rounds of questions. Rounds continued until consensus was achieved. RESULTS: Consensus was achieved for both statements regarding the Professionally Autonomous paramedic system definition in round 2, 85.7% (n = 18). Following analysis and revision of the definition, the additional two statements regarding the Directive paramedic system achieved consensus in round 3, 100% (n = 19). CONCLUSION: This Delphi study was the first study to explore a standardised definition for two newly identified sub-models of the Anglo-American paramedic system with the overall results used to help inform high performing system design for modern Anglo-American paramedic systems into the future.

Theory-Informed Models: Application to Nursing Practice.

The processes for review and confirmation of a theoretical model, its translation into current clinical practice, and the evaluation of outcomes will be presented. The authors' experience at the Seattle Cancer Care Alliance in Washington illustrates the value and relevance of theoretical models in oncology care.

TRIM8 modulates the EWS/FLI oncoprotein to promote survival in Ewing sarcoma.

Fusion-transcription factors (fusion-TFs) represent a class of driver oncoproteins that are difficult to therapeutically target. Recently, protein degradation has emerged as a strategy to target these challenging oncoproteins. The mechanisms that regulate fusion-TF stability, however, are generally unknown. Using CRISPR-Cas9 screening, we discovered tripartite motif-containing 8 (TRIM8) as an E3 ubiquitin ligase that ubiquitinates and degrades EWS/FLI, a driver fusion-TF in Ewing sarcoma. Moreover, we identified TRIM8 as a selective dependency in Ewing sarcoma compared with >700 other cancer cell lines. Mechanistically, TRIM8 knockout led to an increase in EWS/FLI protein levels that was not tolerated. EWS/FLI acts as a neomorphic substrate for TRIM8, defining the selective nature of the dependency. Our results demonstrate that fusion-TF protein stability is tightly regulated and highlight fusion oncoprotein-specific regulators as selective therapeutic targets. This study provides a tractable strategy to therapeutically exploit oncogene overdose in Ewing sarcoma and potentially other fusion-TF-driven cancers.