The Impact of COVID-19 on the Cardiovascular Health of Emerging Adults Aged 18-25: Findings From a Scoping Review.

There is limited knowledge regarding the cardiovascular impact of coronavirus disease 2019 (COVID-19) on emerging adults aged 18-25, a group that disproportionately contracts COVID-19. To guide future cardiovascular disease (CVD) research, policy, and practice, a scoping review was conducted to: (i) examine the impact of the COVID-19 pandemic on the cardiovascular health of emerging adults; and (ii) identify strategies to screen for and manage COVID-19-related cardiovascular complications in this age group. A comprehensive search strategy was applied to several academic databases and grey literature sources. An updated search yielded 6738 articles, 147 of which were extracted and synthesized. Reports identified COVID-19-associated cardiac abnormalities, vascular alterations, and multisystem inflammatory syndrome in emerging adults; based on data from student-athlete samples, prevalence estimates of myocarditis and cardiac abnormalities were 0.5%-3% and 0%-7%, respectively. Obesity, hypertension, CVD, congenital heart disease, and marginalization are potential risk factors for severe COVID-19, related cardiovascular complications, and mortality in this age group. As a screening modality for COVID-19-associated cardiac involvement, it is recommended that cardiac magnetic resonance imaging be indicated by a positive cardiac history and/or abnormal "triad" testing (cardiac troponin, electrocardiogram, and transthoracic echocardiogram) to improve diagnostic utility. To foster long-term cardiovascular health among emerging adults, cardiorespiratory fitness, health literacy and education, and telehealth accessibility should be priorities of health policy and clinical practice. Ultimately, surveillance data from the broader emerging adult population will be crucial to assess the long-term cardiovascular impact of both COVID-19 infection and vaccination, guide screening and management protocols, and inform CVD prevention efforts.

Il existe peu de données portant sur les répercussions de la maladie à coronavirus 2019 (COVID-19) sur le plan cardiovasculaire chez les jeunes adultes âgés de 18 à 25 ans, un groupe contractant la COVID-19 de façon disproportionnée. Afin d'orienter la recherche, les poli-tiques et les pratiques en matière de maladies cardiovasculaires (MCV), un examen exploratoire a été réalisé dans le but i) d'examiner les conséquences de la pandémie de la COVID-19 sur la santé cardiovasculaire des jeunes adultes, et ii) de proposer des stratégies de dépistage et de prise en charge des complications cardiovasculaires associées à la COVID-19 chez les personnes de cette tranche d'âge. Une recherche initiale exhaustive a été réalisée dans plusieurs bases de données universitaires et sources de littérature grise. Les résultats actualisés de cette recherche ont permis de recenser 6 738 articles, dont 147 ont été extraits et synthétisés. Les rapports faisaient état d'anomalies cardiaques, d'altérations vasculaires et de cas du syndrome inflammatoire multisystémique, tous associés à la COVID-19 chez les jeunes adultes. À la lumière des données sur les échantillons d'étudiants-athlètes, la prévalence des myocardites et des anomalies cardiaques se situait respectivement entre 0,5 et 3 %, et entre 0 et 7 % environ. Chez ce même groupe d'âge, l'obésité, l'hypertension, les MCV, les cardiopathies congénitales et la marginalisation constituent des facteurs de risque de COVID-19 sévère, de complications cardiovasculaires associées à la COVID-19 et de mortalité. Dans le cadre du dépistage des atteintes cardiaques associées à la COVID-19, il est recommandé, pour améliorer l'utilité diagnostique, d'indiquer l'imagerie par résonance magnétique cardiaque lors de l'existence d'antécédents cardiaques ou à la suite d'une « triade ¼ de dépistages anormaux (la troponine cardiaque, l'électrocardiogramme et l'échocardiographie transthoracique). Afin de favoriser une bonne santé cardiovasculaire à long terme chez les jeunes adultes, il est recommandé que la capacité cardiorespiratoire, la littératie dans le domaine de la santé, l'éducation et l'accès à la télésanté soient intégrés à titre de priorités dans les politiques de santé et la pratique clinique. En définitive, les données de surveillance portant sur cette large tranche d'âge seront essentielles pour évaluer les répercussions cardiovasculaires à long terme (autant celles d'infections à la COVID-19 que celles de la vaccination), pour orienter les protocoles de dépistage et de prise en charge, ainsi que pour éclairer les efforts de prévention des MCV.

Epigenetic regulation of enhancer of zeste homolog 2 (EZH2) -Yin Yang 1 (YY1) axis in cancer.

In accordance with the World Health Organization, cancer is the second leading cause of death in patients. In recent years, the number of cancer patients has been growing, and the occurrence of cancer in people is becoming more common, primarily due to lifestyle factors. Yin Yang 1 (YY1) is a transcription factor that is widespread throughout. It is a zinc finger protein, falling under the GLI-Kruppel class. YY1 is known to regulate transcriptional activation and repression of various genes associated with different cellular processes such as DNA repair, autophagy, cell survival and apoptosis, and cell division. Meanwhile, EZH2 is a histone-lysine N-methyltransferase enzyme encoded by gene 7 in humans. Its main function involves catalyzing the addition of methyl groups to histone H3 at lysine 27 (H3K27me3), and it is involved in regulating CD8 + T cell fate and function. It is a subunit of a Polycomb repressor complex 2 (PRC2). The EZH2 gene encodes for an enzyme that is involved in histone methylation and transcriptional repression. It adds methyl groups to lysine 27 on histone H3 (H3K27me3) with the help of the cofactor S-adenosyl-L-methionine. In addition to its role in epigenetic regulation, EZH2 also acts as a regulator of CD8+ T cell fate and function. EZH2 has been implicated in T Cell Receptor (TCR) signaling via the regulation of actin polymerization. In fact, EZH2 is involved in numerous signaling pathways that lead to tumorigenesis. EZH2 is mutated in cancer and shows overexpression. Due to its mutation and overexpression, the cells that help combat cancer are suppressed and carcinogenicity is promoted. The association of EZH2 and YY1 poses an intriguing mechanism in relation to cancer.

Interplay between signal transducers and activators of transcription (STAT) proteins and cancer: involvement, therapeutic and prognostic perspective.

Signal transducers and activators of transcription or STAT are proteins that consist of various transcription factors that are responsible for activating genes regarding cell proliferation, differentiation, and apoptosis. They commonly activate several cytokine, growth, or hormone factors via the JAK-STAT signaling pathway by tyrosine phosphorylation which are responsible for giving rise to numerous immune responses. Mutations within the Janus-Kinases (JAKs) or the STATs can set off the commencement of various malfunctions of the immune system of the body; carcinogenesis being an inevitable outcome. STATs are known to act as both oncogenes and tumor suppressor genes which makes it a hot topic of investigation. Various STATs related mechanisms are currently being investigated to analyze its potential of serving as a therapeutic base for numerous immune diseases and cancer; a deeper understanding of the molecular mechanisms involved in the signaling pathways can contribute to the same. This review will throw light upon each STAT member in causing cancer malignancies by affecting subsequent signaling pathways and its genetic and epigenetic associations as well as various inhibitors that could be used to target these pathways thereby devising new treatment options. The review will also focus upon the therapeutic advances made in cancers that most commonly affect people and discuss how STAT genes are identified as prognostic markers.

Diospyros malabarica fruit preparation mediates immunotherapeutic modulation and epigenetic regulation to evoke protection against non-small cell lung cancer (NSCLC).

ETHNOPHARMACOLOGICAL RELEVANCE: Diospyros malabarica is an ethnomedicinal plant with hypoglycaemic, anti-bacterial, and anti-cancer properties and it belongs to the Ebenaceae family which is well known for its medicinal uses since ancient times and application of its bark and unripened fruit has been significantly mentioned in Ayurvedic texts. The Diospyros malabarica species which is known as the Gaub in Hindi and Indian Persimmon in English is native to India, however, it is distributed throughout the tropics. AIM OF THE STUDY: As Diospyros malabarica fruit preparation (DFP) possesses medicinal values, the study aims to evaluate its role as natural, non-toxic, and cost-effective dendritic cells (DCs) maturing immunomodulatory agent and also as an epigenetic regulator to combat Non-small cell lung cancer (NSCLC) which is a type of lung cancer whose treatment options such as chemotherapy, radiation therapy, etc. are accompanied with some adverse side effects. Thus, immunotherapeutic strategies are in high demand to evoke tumor protective immunity against NSCLC without causing such side effects. MATERIALS AND METHODS: Peripheral Mononuclear Cells (PBMCs) derived monocytes of normal subjects and NSCLC patients were utilized to generate DCs matured with either LPS (LPSDC) or DFP (DFPDC). Mixed Lymphocyte Reaction (MLR) was carried out with the differentially matured DCs co-culturing T cells and cytotoxicity of lung cancer cells (A549) was measured through LDH release assay and cytokine profiling was carried out via ELISA respectively. PBMCs of normal subjects and NSCLC patients have transfected separately in vitrowith CRISPR-activation plasmid of p53 and CRISPR-Cas9 knockout plasmid of c-Myc to analyze epigenetic mechanism(s) in the presence and absence of DFP. RESULTS: Diospyros malabarica fruit preparation (DFP) treated DC upregulates the secretion of T helper (TH)1 cell specific cytokines (IFN-γ and IL-12) and signal transducer and activator of transcription molecules (STAT1 and STAT4). Furthermore, it also downregulates the secretion of TH2-specific cytokines (IL-4 and IL-10). Diospyros malabarica fruit preparation (DFP) enhances p53 expression by reducing methylation levels at the CpG island of the promoter region. Upon c-Myc knockout, epigenetic markers such as H3K4Me3, p53, H3K14Ac, BRCA1, and WASp were enhanced whereas H3K27Me3, JMJD3, and NOTCH1 were downregulated. CONCLUSION: Diospyros malabarica fruit preparation (DFP) not only increases the expression of type 1 specific cytokines but also augments tumor suppression modulating various epigenetic markers to evoke tumor protective immunity without any toxic activities.

Blood Chromium Levels and Their Association with Cardiovascular Diseases, Diabetes, and Depression: National Health and Nutrition Examination Survey (NHANES) 2015-2016.

Currently, there is no global consensus about the essentiality of dietary chromium. To provide evidence to this debate, an examination of blood chromium levels and common chronic health conditions was undertaken. Using a subsample from the 2015−2016 US National Health and Nutrition Examination Survey (n = 2894; 40 years+), chi-square and binary logistic regression analyses were conducted to examine blood chromium levels (0.7−28.0 vs. <0.7 µg/L) and their associations with cardiovascular diseases (CVDs; self-report), diabetes mellitus (DM; glycohemoglobin ≥5.7%), and depression (Patient Health Questionnaire-9 score ≥5), while controlling for socio-demographic (age/sex/income/education/relationship status) and health-related (red blood cell folate/medications/co-morbidities/body mass index (BMI)/substance use) factors. The sample was almost evenly distributed between men and women (n = 1391, 48.1% (men); n = 1503, 51.9% (women)). The prevalence estimates of low blood chromium levels tended to be higher among those with CVDs (47.4−47.6%) and DM (50.0−51.6%). Comparisons between those with low vs. normal blood chromium levels indicate men have increased odds of CVDs (adjusted odds ratio (aOR) = 1.86, 95% confidence interval (CI): 1.22−2.85, p < 0.001) and DM (aOR = 1.93, 95% CI: 1.32−2.83, p < 0.001) and lower odds of depression (aOR = 0.42, 95% CI: 0.22−0.77, p < 0.05). Dietary chromium may be important in the prevention and management of CVDs and DM for men. Continued exploration of chromium's role in chronic diseases, including differences by biological factors, is needed.

A Rapid Realist Review of Effective Mental Health Interventions for Individuals with Chronic Physical Health Conditions during the COVID-19 Pandemic Using a Systems-Level Mental Health Promotion Framework.

The 2020 global outbreak of COVID-19 exposed and heightened threats to mental health across societies. Research has indicated that individuals with chronic physical health conditions are at high risk for suffering from severe COVID-19 illness and from the adverse consequences of public health responses to COVID-19, such as social isolation. This paper reports on the findings of a rapid realist review conducted alongside a scoping review to explore contextual factors and underlying mechanisms or drivers associated with effective mental health interventions within and across macro-meso-micro systems levels for individuals with chronic physical health conditions. This rapid realist review extracted 14 qualified studies across 11 countries and identified four key mechanisms from COVID-19 literature-trust, social connectedness, accountability, and resilience. These mechanisms are discussed in relation to contextual factors and outcomes reported in the COVID literature. Realist reviews include iterative searches to refine their program theories and context-mechanism-outcome explanations. A purposive search of pre-COVID realist reviews on the study topic was undertaken, looking for evidence of the robustness of these mechanisms. There were differences in some of the pre-COVID mechanisms due to contextual factors. Importantly, an additional mechanism-power-sharing-was highlighted in the pre-COVID literature, but absent in the COVID literature. Pre-existing realist reviews were used to identify potential substantive theories and models associated with key mechanisms. Based on the overall findings, implications are provided for mental health promotion policy, practice, and research.

Interventions to Support Mental Health among Those with Health Conditions That Present Risk for Severe Infection from Coronavirus Disease 2019 (COVID-19): A Scoping Review of English and Chinese-Language Literature.

This study aimed to address knowledge gaps related to the prevention and management of mental health responses among those with a condition that presents risk of severe COVID-19 infection. A scoping review that mapped English and Chinese-language studies (2019-2020) located in MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Sociological Abstracts, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Airiti Library was undertaken. Search terms related to COVID-19, mental health, and physical health were used and articles that included all three of these factors were extracted (n = 77). With the exception of one hospital-based pilot study, there were no intervention studies targeting mental health in those at risk of severe COVID-19 infection. Promising practices such as integrated care models that appropriately screen for mental health issues, address health determinants, and include use of digital resources were highlighted. Patient navigator programs, group online medical visits, peer support, and social prescribing may also support those with complex needs. Future policies need to address digital health access inequities and the implementation of multi-integrated health and social care. Furthermore, research is needed to comprehensively assess multi-integrated interventions that are resilient to public health crises.

Viral evolution identifies a regulatory interface between paramyxovirus polymerase complex and nucleocapsid that controls replication dynamics.

Paramyxoviruses are negative-polarity RNA viruses of major clinical importance. The dynamic interaction of the RNA-dependent RNA polymerase (RdRP) complex with the encapsidated RNA genome is mechanistically and structurally poorly understood. Having generated recombinant measles (MeV) and canine distemper (CDV) viruses with truncated nucleocapsid (N) protein showing defects in replication kinetics, we have applied a viral evolution approach to the problem. Passaging of recombinants resulted in long-range compensatory mutations that restored RdRP bioactivity in minigenome assays and efficient replication of engineered viruses. Compensatory mutations clustered at an electronically compatible acidic loop in N-core and a basic face of the phosphoprotein X domain (P-XD). Co-affinity precipitations, biolayer interferometry, and molecular docking revealed an electrostatic-driven transiently forming interface between these domains. The compensatory mutations reduced electrostatic compatibility of these microdomains and lowered coprecipitation efficiency, consistent with a molecular checkpoint function that regulates paramyxovirus polymerase mobility through modulation of conformational stability of the P-XD assembly.

Patient Empowerment: The Role of Technology.

Patient empowerment is a buzzword that has gained much currency in recent years. It is defined as a process that helps people gain control over their own lives and increases their capacity to act on issues that they themselves define as important. This paper outlines the problems faced by the current medical model of patient empowerment and proposes a unique framework for patient empowerment that provides guidance on how health technology supports or detracts from empowering patients and families. The paper provides an ethical lens for physicians, policymakers, patients, and families in the health care system to consider the central role of the principles of autonomy and justice in patient empowerment. This paper also discusses how technology can be used to further patient empowerment and patient-centeredness of health care systems.

Privacy and Policy Implications for Big Data and Health Information Technology for Patients: A Historical and Legal Analysis.

The consideration of privacy and policy implications for big data is essential to designing patient-centered health technology. A literature review demonstrated a significant gap to moving forward with information technology in healthcare. Ovid Medline and Google Scholar were searched to identify papers related to health technology, patient outcomes, and policy implications of Big Data. The findings of this research showed that despite a robust legal framework and clear outline of the legislation, there exists an innovative opportunity for health technologies to evolve and become patient-centered by integrating privacy and policy knowledge in health information technology. This historical legal analysis is valuable to health system leaders, decision-makers, health technology companies that are creating innovative platforms, and clinicians in both Canada and the United States.

The Unstructured Paramyxovirus Nucleocapsid Protein Tail Domain Modulates Viral Pathogenesis through Regulation of Transcriptase Activity.

The paramyxovirus replication machinery comprises the viral large (L) protein and phosphoprotein (P-protein) in addition to the nucleocapsid (N) protein, which encapsidates the single-stranded RNA genome. Common to paramyxovirus N proteins is a C-terminal tail (Ntail). The mechanistic role and relevance for virus replication of the structurally disordered central Ntail section are unknown. Focusing initially on members of the Morbillivirus genus, a series of measles virus (MeV) and canine distemper virus (CDV) N proteins were generated with internal deletions in the unstructured tail section. N proteins with large tail truncations remained bioactive in mono- and polycistronic minireplicon assays and supported efficient replication of recombinant viruses. Bioactivity of Ntail mutants extended to N proteins derived from highly pathogenic Nipah virus. To probe an effect of Ntail truncations on viral pathogenesis, recombinant CDVs were analyzed in a lethal CDV/ferret model of morbillivirus disease. The recombinant viruses displayed different stages of attenuation ranging from ameliorated clinical symptoms to complete survival of infected animals, depending on the molecular nature of the Ntail truncation. Reinfection of surviving animals with pathogenic CDV revealed robust protection against a lethal challenge. The highly attenuated virus was genetically stable after ex vivo passaging and recovery from infected animals. Mechanistically, gradual viral attenuation coincided with stepwise altered viral transcriptase activity in infected cells. These results identify the central Ntail section as a determinant for viral pathogenesis and establish a novel platform to engineer gradual virus attenuation for next-generation paramyxovirus vaccine design.IMPORTANCE Investigating the role of the paramyxovirus N protein tail domain (Ntail) in virus replication, we demonstrated in this study that the structurally disordered central Ntail region is a determinant for viral pathogenesis. We show that internal deletions in this Ntail region of up to 55 amino acids in length are compatible with efficient replication of recombinant viruses in cell culture but result in gradual viral attenuation in a lethal canine distemper virus (CDV)/ferret model. Mechanistically, we demonstrate a role of the intact Ntail region in the regulation of viral transcriptase activity. Recombinant viruses with Ntail truncations induce protective immunity against lethal challenge of ferrets with pathogenic CDV. This identification of the unstructured central Ntail domain as a nonessential paramyxovirus pathogenesis factor establishes a foundation for harnessing Ntail truncations for vaccine engineering against emerging and reemerging members of the paramyxovirus family.

Public Spending on Health Service and Policy Research in Canada, the United Kingdom, and the United States: A Modest Proposal.

Health services and policy research (HSPR) represent a multidisciplinary field which integrates knowledge from health economics, health policy, health technology assessment, epidemiology, political science among other fields, to evaluate decisions in health service delivery. Health service decisions are informed by evidence at the clinical, organizational, and policy level, levels with distinct, managerial drivers. HSPR has an evolving discourse spanning knowledge translation, linkage and exchange between research and decision-maker partners and more recently, implementation science and learning health systems. Local context is important for HSPR and is important in advancing health reform practice. The amounts and configuration of national investment in this field remain important considerations which reflect priority investment areas. The priorities set within this field or research may have greater or lesser effects and promise with respect to modernizing health services in pursuit of better value and better population outcomes. Within Canada an asset map for HSPR was published by the national HSPR research institute. Having estimated publicly-funded research spending in Canada, we sought identify best available comparable estimates from the United States and the United Kingdom. Investments from industry and charitable organizations were not included in these numbers. This commentary explores spending by the United States, Canada, and the United Kingdom on HSPR as a fraction of total public spending on health and the importance of these respective investments in advancing health service performance. Proposals are offered on the merits of common nomenclature and accounting for areas of investigation in pursuit of some comparable way of assessing priority HSPR investments and suggestions for earmarking such investments to total investment in health services spending.

The structurally disordered paramyxovirus nucleocapsid protein tail domain is a regulator of the mRNA transcription gradient.

The paramyxovirus RNA-dependent RNA-polymerase (RdRp) complex loads onto the nucleocapsid protein (N)-encapsidated viral N:RNA genome for RNA synthesis. Binding of the RdRp of measles virus (MeV), a paramyxovirus archetype, is mediated through interaction with a molecular recognition element (MoRE) located near the end of the carboxyl-terminal Ntail domain. The structurally disordered central Ntail section is thought to add positional flexibility to MoRE, but the functional importance of this Ntail region for RNA polymerization is unclear. To address this question, we dissected functional elements of Ntail by relocating MoRE into the RNA-encapsidating Ncore domain. Linker-scanning mutagenesis identified a microdomain in Ncore that tolerates insertions. MoRE relocated to Ncore supported efficient interaction with N, MoRE-deficient Ntails had a dominant-negative effect on bioactivity that was alleviated by insertion of MoRE into Ncore, and recombinant MeV encoding N with relocated MoRE grew efficiently and remained capable of mRNA editing. MoRE in Ncore also restored viability of a recombinant lacking the disordered central Ntail section, but this recombinant was temperature-sensitive, with reduced RdRp loading efficiency and a flattened transcription gradient. These results demonstrate that virus replication requires high-affinity RdRp binding sites in N:RNA, but productive RdRp binding is independent of positional flexibility of MoRE and cis-acting elements in Ntail. Rather, the disordered central Ntail section independent of the presence of MoRE in Ntail steepens the paramyxovirus transcription gradient by promoting RdRp loading and preventing the formation of nonproductive polycistronic viral mRNAs. Disordered Ntails may have evolved as a regulatory element to adjust paramyxovirus gene expression.

Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors.

Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by using a recombinant RSV reporter virus to expand the pool of RSV inhibitor candidates. Mechanistic characterization revealed that a potent newly identified inhibitor class blocks viral entry through specific targeting of the RSV fusion (F) protein. Resistance against this class was induced and revealed overlapping hotspots with diverse, previously identified RSV entry blockers at different stages of preclinical and clinical development. A structural and biochemical assessment of the mechanism of unique, broad RSV cross-resistance against structurally distinct entry inhibitors demonstrated that individual escape hotspots are located in immediate physical proximity in the metastable conformation of RSV F and that the resistance mutations lower the barrier for prefusion F triggering, resulting in an accelerated RSV entry kinetics. One resistant RSV recombinant remained fully pathogenic in a mouse model of RSV infection. By identifying molecular determinants governing the RSV entry machinery, this study spotlights a molecular mechanism of broad RSV resistance against entry inhibition that may affect the impact of diverse viral entry inhibitors presently considered for clinical use and outlines a proactive design for future RSV drug discovery campaigns.

Easing the strain on a pediatric tertiary care center: use of a redistribution system.

OBJECTIVE: To evaluate the ability of a regionalized system to safely transfer patients requiring admission from a referral center to either regional or community hospitals. DESIGN: Cohort study of children requiring admission. Following transfer, a questionnaire was administered to eligible caregivers. Subsequent emergency department (ED) use was assessed by comparing children who were transferred with those who were not. SETTING: The Hospital for Sick Children, Toronto, Ontario, Canada, from April 1, 2003, through March 31, 2004. PARTICIPANTS: Caregivers of 371 children who underwent transfer from a tertiary care center ED to either a regional or a community hospital were eligible; 344 were contacted. Two hundred fifty-three children for whom transfer was considered but was not performed served as a comparison group. Intervention Questionnaire administered to caregivers, combined with database review. MAIN OUTCOME MEASURES: Failure of the transfer process, caregiver satisfaction, and future tertiary care center ED use. RESULTS: Five children experienced intravenous access problems, and 4 children experienced delayed antibiotic administration. Caregiver satisfaction was 92.3% with the transfer process and 84.4% with the care at the receiving hospital. Forty-seven percent of caregivers indicated that they would agree to a similar transfer in the future. Two years later, fewer transferred children (39.9%) than those who were not transferred (49.6%) had revisited the tertiary care center ED (odds ratio, 1.52; 95% confidence interval, 1.10-2.10). The mean number of visits was unchanged (95% confidence interval of the difference, -0.44 to 0.21 visits). CONCLUSIONS: Although we found the redistribution program to be safe, caregivers stated a preference not to be transferred again. The redistribution system did not substantially alter tertiary care center ED use.