Rheumatic Care in Under-Resourced Areas Using the Extension for Community Healthcare Outcomes Model.

OBJECTIVE: To demonstrate the effectiveness of the Extension for Community Healthcare Outcomes (Project ECHO) in educating primary care clinicians (PCCs) to provide best practice rheumatic care to patients in under-resourced communities in New Mexico. METHODS: Attendee data for weekly teleECHO sessions, lectures, grand rounds, and mini-residency trainings were evaluated from June 2006 to June 2014. Participant feedback was evaluated from January 2009 to December 2014, when the program was approved for continuing medical education (CME) credits. Retrospective review of diagnoses associated with case presentations was conducted from June 2006 to June 2014 to evaluate the types of cases presented. A focus group was conducted with a convenience sample of 8 New Mexico PCCs who participated in ECHO Rheumatology (ECHO Rheum) for 1 year or longer. RESULTS: Over the course of 9 years, ECHO Rheum educated 2,230 clinicians, consisting primarily of physicians (53%) and nurse practitioners (22%). A total of 1,958 CME credits were awarded to those who participated. There were 1,173 cases presented; 85% of the cases reflected the 3 most common diagnoses: rheumatoid arthritis (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). In addition, ECHO Rheum conducted 15 two-day mini-residencies involving 30 PCCs; 21 of these clinicians subsequently completed the American College of Rheumatology online certification. CONCLUSION: Results from this study demonstrate that participation in ECHO Rheum provides clinicians in under-resourced areas access to best-practice knowledge and training in rheumatology.

A Novel Intervention for High-Need, High-Cost Medicaid Patients: a Study of ECHO Care.

BACKGROUND: A small number of high-need patients account for a disproportionate amount of Medicaid spending, yet typically engage little in outpatient care and have poor outcomes. OBJECTIVE: To address this issue, we developed ECHO (Extension for Community Health Outcomes) Care™, a complex care intervention in which outpatient intensivist teams (OITs) provided care to high-need high-cost (HNHC) Medicaid patients. Teams were supported using the ECHO model™, a continuing medical education approach that connects specialists with primary care providers for case-based mentoring to treat complex diseases. DESIGN: Using an interrupted time series analysis of Medicaid claims data, we measured healthcare utilization and expenditures before and after ECHO Care. PARTICIPANTS: ECHO Care served 770 patients in New Mexico between September 2013 and June 2016. Nearly all had a chronic mental illness, and over three-quarters had a chronic substance use disorder. INTERVENTION: ECHO Care patients received care from an OIT, which typically included a nurse practitioner or physician assistant, a registered nurse, a licensed mental health provider, and at least one community health worker. Teams focused on addressing patients' physical, behavioral, and social issues. MAIN MEASURES: We assessed the effect of ECHO Care on Medicaid costs and utilization (inpatient admissions, emergency department (ED) visits, other outpatient visits, and dispensed prescriptions. KEY RESULTS: ECHO Care was associated with significant changes in patients' use of the healthcare system. At 12 months post-enrollment, the odds of a patient having an inpatient admission and an ED visit were each reduced by approximately 50%, while outpatient visits and prescriptions increased by 23% and 8%, respectively. We found no significant change in overall Medicaid costs associated with ECHO Care. CONCLUSIONS: ECHO Care shifts healthcare utilization from inpatient to outpatient settings, which suggests decreased patient suffering and greater access to care, including more effective prevention and early intervention for chronic conditions.

ECHO Care: Providing Multidisciplinary Specialty Expertise to Support the Care of Complex Patients.

BACKGROUND: Programs for high-need, high-cost (HNHC) patients can improve care and reduce costs. However, it may be challenging to implement these programs in rural and underserved areas, in part due to limited access to specialty consultation. AIM: Evaluate the feasibility of using the Extension for Community Health Outcomes (ECHO) model to provide specialist input to outpatient intensivist teams (OITs) dedicated to caring for HNHC patients. SETTING: Weekly group videoconferencing sessions that connect multidisciplinary specialists with OITs. PARTICIPANTS: Six OITs across New Mexico, typically consisting of a nurse practitioner or physician assistant, a registered nurse, a counselor or social worker, and at least one community health worker. PROGRAM DESCRIPTION: OITs and specialists participated in weekly teleECHO sessions focused on providing the OITs with case-based mentoring and support. PROGRAM EVALUATION: OITs and specialists discussed 427 highly complex patient cases, many of which had social or behavioral health components to address. In 70% of presented cases, the teams changed their care plan for the patient, and 87% reported that they applied what they learned in hearing case presentations to other HNHC patients. DISCUSSION: Pairing the ECHO model with intensive outpatient care is a feasible strategy to support OITs to provide high-quality care for HNHC patients.

Making the Mark: The Role of Adenosine Modifications in the Life Cycle of RNA Viruses.

Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating life cycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral life cycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2' O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies.

STAT4-mediated transcriptional repression of the IL5 gene in human memory Th2 cells.

Type I interferon (IFN-α/ß) plays a critical role in suppressing viral replication by driving the transcription of hundreds of interferon-sensitive genes (ISGs). While many ISGs are transcriptionally activated by the ISGF3 complex, the significance of other signaling intermediates in IFN-α/ß-mediated gene regulation remains elusive, particularly in rare cases of gene silencing. In human Th2 cells, IFN-α/ß signaling suppressed IL5 and IL13 mRNA expression during recall responses to T-cell receptor (TCR) activation. This suppression occurred through a rapid reduction in the rate of nascent transcription, independent of de novo expression of ISGs. Further, IFN-α/ß-mediated STAT4 activation was required for repressing the human IL5 gene, and disrupting STAT4 dimerization reversed this effect. This is the first demonstration of STAT4 acting as a transcriptional repressor in response to IFN-α/ß signaling and highlights the unique activity of this cytokine to acutely block the expression of an inflammatory cytokine in human T cells.

Interferon at the crossroads of allergy and viral infections.

IFN-α/ß was first described as a potent inhibitor of viral replication, but it is now appreciated that IFN signaling plays a pleiotropic role in regulating peripheral T cell functions. Recently, IFN-α/ß was shown to block human Th2 development by suppressing the transcription factor GATA3. This effect is consistent with the role for IFN-α/ß in suppressing allergic inflammatory processes by blocking granulocyte activation and IL-4-mediated B cell isotype switching to IgE. With the consideration of recent studies demonstrating a defect in IFN-α/ß secretion in DCs and epithelial cells from individuals with severe atopic diseases, there is an apparent reciprocal negative regulatory loop in atopic individuals, whereby the lack of IFN-α/ß secretion by innate cells contributes to the development of allergic Th2 cells. Is it possible to overcome these events by treating with IFN-α/ß or by inducing its secretion in vivo? In support of this approach, case studies have documented the therapeutic potential of IFN-α/ß in treating steroid-resistant allergic asthma and other atopic diseases. Additionally, individuals with asthma who are infected with HCV and respond to IFN therapy showed a reduction in symptoms and severity of asthma attacks. These findings support a model, whereby allergic and antiviral responses are able to cross-regulate each other, as IgER cross-linking of pDCs prevents IFN-α/ß production in response to viral infection. The clinical importance of upper-respiratory viruses in the context of allergic asthma supports the need to understand how these pathways intersect and to identify potential therapeutic targets.

IFN-α suppresses GATA3 transcription from a distal exon and promotes H3K27 trimethylation of the CNS-1 enhancer in human Th2 cells.

CD4(+) Th2 development is regulated by the zinc finger transcription factor GATA3. Once induced by acute priming signals, such as IL-4, GATA3 poises the Th2 cytokine locus for rapid activation and establishes a positive-feedback loop that maintains elevated GATA3 expression. Type I IFN (IFN-α/ß) inhibits Th2 cells by blocking the expression of GATA3 during Th2 development and in fully committed Th2 cells. In this study, we uncovered a unique mechanism by which IFN-α/ß signaling represses the GATA3 gene in human Th2 cells. IFN-α/ß suppressed expression of GATA3 mRNA that was transcribed from an alternative distal upstream exon (1A). This suppression was not mediated through DNA methylation, but rather by histone modifications localized to a conserved noncoding sequence (CNS-1) upstream of exon 1A. IFN-α/ß treatment led to a closed conformation of CNS-1, as assessed by DNase I hypersensitivity, along with enhanced accumulation of H3K27me3 mark at this CNS region, which correlated with increased density of total nucleosomes at this putative enhancer. Consequently, accessibility of CNS-1 to GATA3 DNA binding activity was reduced in response to IFN-α/ß signaling, even in the presence of IL-4. Thus, IFN-α/ß disrupts the GATA3-autoactivation loop and promotes epigenetic silencing of a Th2-specific regulatory region within the GATA3 gene.