Pediatric Learning Health Networks in Solid Organ Transplantation-Engaging all Stakeholders to Achieve Health for Children Who Require Transplantation.

BACKGROUND: Learning Health Networks (LHN) have evolved within medicine over the past two decades, but their integration into transplantation has been more recent. OBJECTIVES AND METHODS: In this paper, we describe three LHNs in end-stage organ disease/transplantation, their common and unique features, and how their "actor-oriented" architecture allowed for rapid adaptation to meet the needs of their patients and practitioners during the recent COVID-19 pandemic. RESULT: The structure and focus of the Improving Renal Outcomes Collaborative (IROC), Starzl Network for Excellence in Pediatric Transplantation (SNEPT), and the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) are reviewed. We discuss the critical role of patient and family engagement, focusing on collaboration with Transplant Families. Finally, we review challenges common to the LHN concept and potential common areas of alignment to achieve the goal of more rapid and sustained progress to improve health in pediatric transplantation. CONCLUSION: LHN in transplantation are essential to accelerate knowledge dissemination and improve outcomes.

Reducing donor acceptance practice variation - Learnings from a discussion forum.

PURPOSE: Although waitlist mortality is unacceptably high, nearly half of donor heart offers are rejected by pediatric heart transplant centers. The Advanced Cardiac Therapy Improving Outcome Network (ACTION) and Pediatric Heart Transplant Society (PHTS) convened a multi-institutional donor decision discussion forum (DDDF) aimed at assessing donor acceptance practices and reducing practice variation. METHODS: A 1-h-long virtual DDDF for providers across North America, the United Kingdom, and Brazil was held monthly. Each session typically included two case presentations posing a real-world donor decision challenge. Attendees were polled before the presenting center's decision was revealed. Group discussion followed, including a review of relevant literature and PHTS data. Metrics of participation, participant agreement with presenting center decisions, and impact on future decision-making were collected and analyzed. RESULTS: Over 2 years, 41 cases were discussed. Approximately 50 clinicians attended each call. Risk factors influencing decision-making included donor quality (10), size discrepancy (8), and COVID-19 (8). Donor characteristics influenced 63% of decisions, recipient factors 35%. Participants agreed with the decision made by the presenting center only 49% of the time. Post-presentation discussion resulted in 25% of participants changing their original decision. Survey conducted reported that 50% respondents changed their donor acceptance practices. CONCLUSION: DDDF identified significant variation in pediatric donor decision-making among centers. DDDF may be an effective format to reduce practice variation, provide education to decision-makers, and ultimately increase donor utilization.

Patient and parent-reported outcomes in paediatric ventricular assist device support: a multi-center ACTION learning network feasibility and pilot experience.

BACKGROUND: Patient- and proxy-reported outcomes (PROs) are an important indicator of healthcare quality and can be used to inform treatment. Despite the widescale use of PROs in adult cardiology, they are underutilised in paediatric cardiac care. This study describes a six-center feasibility and pilot experience implementing PROs in the paediatric and young adult ventricular assist device population. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative learning network comprised of 55 centres focused on improving clinical outcomes and the patient/family experience for children with heart failure and those supported by ventricular assist devices. The development of ACTION's PRO programme via engagement with patient and parent stakeholders is described. Pilot feasibility, patient/parent and clinician feedback, and initial PRO findings of patients and families receiving paediatric ventricular assist support across six centres are detailed. RESULTS: Thirty of the thirty-five eligible patients (85.7%) were enrolled in the PRO programme during the pilot study period. Clinicians and participating patients/parents reported positive experiences with the PRO pilot programme. The most common symptoms reported by patients/parents in the first month post-implant period included limitations in activities, dressing change distress, and post-operative pain. Poor sleep, dressing change distress, sadness, and fatigue were the most common symptoms endorsed >30 days post-implant. Parental sadness and worry were notable throughout the entirety of the post-implant experience. CONCLUSIONS: This multi-center ACTION learning network-based PRO programme demonstrated initial success in this six-center pilot study experience and yields important next steps for larger-scale PRO collection, research, and clinical intervention.

Considerations for Advanced Heart Failure Consultation in Individuals With Fontan Circulation: Recommendations From ACTION.

Individuals with Fontan circulation are at risk of late mortality from both cardiac and noncardiac causes. Despite the known risk of mortality, referral indications for advanced heart failure care vary between centers, and many individuals die from Fontan circulation-related complications either after late consideration for advanced heart failure therapies or having never seen a heart failure specialist. There is a critical need for guidelines to direct appropriately timed referral for advanced heart failure consultation. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Fontan Committee has developed recommended thresholds for advanced heart failure referral to guide primary cardiologists. These recommendations are divided into 4 categories of clinical Fontan circulatory dysfunction including (1) cardiac/systemic ventricular dysfunction, (2) Fontan pathway dysfunction, (3) lymphatic dysfunction, and (4) extracardiac dysfunction.

Heroism and paramedic practice: A constructivist metasynthesis of qualitative research.

Objectives: We aimed to identify, appraise, and synthesise the qualitative literature to develop theory on heroism and paramedic practice. Hypothesis/research question: What does published literature tell us about heroism and paramedic practice? Setting: Paramedics and other healthcare workers (HCWs) faced an outpouring of public support for them early in the COVID-19 pandemic which brought into focus the relationship between them and society, where they are portrayed as heroes. Participants: We conducted a metasynthesis using Evolved Grounded Theory and procedural guidelines of Noblit and Hare to guide analysis. Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) guidelines were also applied. Results: 151 papers were retrieved and eleven included in the final sample. Studies were moderate to very low quality, involving a wide range of methodologies and settings; none specifically explored heroism and paramedic practice. The following interrelated themes were constructed on heroism and paramedic practice: (a) Myth, Folk law, and storytelling in heroism and paramedic practice (b) The epic journey of heroism and paramedic practice (c) Heroes and Zeroes: The fluctuating Societal Value in heroism and paramedic practice (d) Politicisation, and objectification in Heroism and Paramedic practice. Conclusion: Paramedics have long been characterised as heroes, but this may not reflect their everyday experiences. Heroism in paramedic practice can provide scripts for prosocial action, inspiring others, and leading to more social heroic actions. Paramedics may however be ambivalent to such heroism narratives, due to politicisation, and objectification in the media and society. This metasynthesis is only one of many possible constructions of heroism and paramedic practice and is the first point in making sense of and developing theory on heroism and paramedic practice. Study registration: PROSPERO: CRD42021234851.

Protocol for a constructivist metasynthesis of qualitative research of heroism and paramedic practice.

BACKGROUND: Exceptional demands have been placed on paramedics and other healthcare workers (HCWs) during the COVID-19 pandemic. An overwhelming outpouring of public support has unfolded, bringing into focus the relationship between paramedics, other HCWs and society, where they are portrayed as heroes. Scholars have studied the notion of heroism to society, and characteristics of such heroic status include: the voluntary nature of a heroic act, risk of physical or social harm, willingness to accept the consequences of action, acting for the benefit of others and without the expectation of gain. While some HCWs and paramedics may reflect these characteristics, many may not. Such heroic narratives can be damaging, stifling meaningful discussion around limits to duties, failing to acknowledge the importance of reciprocity and potentially imposing demands on paramedics and HCWs to be heroic. AIM: This article prospectively presents the protocol for a metasynthesis which aims to identify, appraise and synthesise the qualitative literature in order to develop theory on heroism and paramedic practice. METHODS: Evolved grounded theory methodology is followed along with the procedural guidelines of Noblit and Hare (1988) to guide the analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P) have also been adopted when preparing this protocol and will be followed in the study proper. The protocol has been registered with the International Prospective Register of Systematic Reviews PROSPERO 2021, registration number CRD42021234851. RESULTS: We do not currently have results, but PRISMA guidelines will be followed when reporting our findings. CONCLUSION: Current narratives on heroism and paramedic practice are important in terms of the relationship between paramedics and society. The metasynthesis prospectively reported in this article serves as the first point in our journey of making sense of and developing theory on heroism and paramedic practice.

The Creation of a Pediatric Health Care Learning Network: The ACTION Quality Improvement Collaborative.

Improving the outcomes of pediatric patients with congenital heart disease with end-stage heart failure depends on the collaboration of all stakeholders; this includes providers, patients and families, and industry representatives. Because of the rarity of this condition and the heterogeneity of heart failure etiologies that occur at pediatric centers, learnings must be shared between institutions and all disciplines to move the field forward. To foster collaboration, excel discovery, and bring data to the bedside, a new, collaborative quality improvement science network-ACTION (Advanced Cardiac Therapies Improving Outcomes Network)-was developed to meet the needs of the field. Existing gaps in care and the methods of improvement that will be used are described, along with the mission and vision, utility of real-world data for regulatory purposes, and the organizational structure of ACTION is described.

Development of an Orthotopic Intrasplenic Xenograft Mouse Model of Canine Histiocytic Sarcoma and Its Use in Evaluating the Efficacy of Treatment with Dasatinib.

Canine histiocytic sarcoma is a highly aggressive and metastatic hematopoietic neoplasm that responds poorly to currently available treatment regimens. Our goal was to establish a clinically relevant xenograft mouse model to assess the preclinical efficacy of novel cancer treatment protocols for histiocytic sarcoma. We developed an intrasplenic xenograft mouse model characterized by consistent tumor growth and development of metastasis to the liver and other abdominal organs. This model represents the metastatic or disseminated form of canine histiocytic sarcoma, which is considered the most clinically challenging form of the disease. Transfection of tumor cells with a luciferase vector supported the use of in vivo bioluminescence imaging to track tumor progression over time and to assess the response of this murine model to novel chemotherapeutic agents. Dasatinib treatment of the mice with intrasplenic xenografts decreased tumor growth and increased survival times, compared with mice treated with vehicle only. Our findings indicate the potential of dasatinib for the treatment of histiocytic sarcoma in dogs and for similar diseases in humans. These results warrant additional studies to clinically test the efficacy of dasatinib in dogs with histiocytic sarcoma.

Activating Mutations in PTPN11 and KRAS in Canine Histiocytic Sarcomas.

While the genetic contributions to the predisposition of Bernese mountain dogs (BMDs) to histiocytic sarcoma (HS) remains unclear, some insights into key genetic drivers have been gained. Our group recently reported a mutation in the PTPN11 gene (E76K). We have now identified a second missense mutation in PTPN11 (G503V), and a mutation in KRAS (Q61H) present in HS cell lines. These mutations are associated with malignancies in humans, and known to be gain-of-function mutations that result in activation of the mitogen-activated protein kinase (MAPK) pathway. The goal of the present study was to evaluate the prevalence of these mutations in a large sample of HS cases from BMDs and golden retrievers, and in lymphoma cases, from a cohort of BMDs. Mutations in PTPN11 were present in HS in 41/96 (43%) BMDs, and in 3/13 (23%) golden retrievers. PTPN11 mutations E76K and G503V did not coexist in the same neoplasm. The KRAS mutation was much less frequent, with a prevalence of 3.1% (3/96). We did not identify either PTPN11 nor KRAS mutations in any of the lymphoma samples. These results point out the potential relevance of PTPN11 and KRAS mutations as activators of the oncogenic MAPK pathway for canine HS, particularly in BMDs.

Collaboration and new data in ACTION: a learning health care system to improve pediatric heart failure and ventricular assist device outcomes.

Outcomes in pediatric heart failure and ventricular assist devices (VADs) remain suboptimal. Given the complexity and limited numbers, centers cannot be expected to acquire mastery and generalizable knowledge independently. Recognizing this problem, the community has formed Advanced Cardiac Therapies Improving Outcomes Network (ACTION), a collaborative learning health care system committed to unrelenting collaboration and continuous learning to improve critical outcomes in pediatric heart failure. ACTION is inclusive of all interested parties and believes the fastest and most effective way to make progress is through working together. ACTION's approaches to collaboration and data sharing will be highlighted.