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BackgroundIncreasing electronic health information exchange (HIE) between provider organizations is a top policy priority that has been pursued by establishing varied types of networks.ObjectivesTo measure electronic connectivity enabled by these networks, including community, electronic health record vendor, and national HIE networks, across US hospitals weighted by the volume of shared patients and identify characteristics that predict connectivity.Research designCross-sectional analysis of 1721 hospitals comprising 16,344 hospital pairs and 6,492,232 shared patients from 2018 CareSet Labs HOP data and national hospital surveys.SubjectsPairs of US acute care hospitals that delivered care to 11 or more of the same fee-for-service Medicare beneficiaries in 2018.MeasuresWhether a patient was treated by a pair of hospitals connected through participation in the same HIE network ("connected hospitals") or not connected because the hospitals participated in different networks, only 1 participated, or both did not participate.ResultsSixty-four percent of shared patients were treated by connected hospitals. Of the remaining shared patients, 14% were treated by hospital pairs that participated in different HIE networks, 21% by pairs in which only 1 hospital participated in an HIE network, and 2% by pairs in which neither participated. Patients treated by pairs with at least 1 for-profit hospital, and by pairs located in competitive markets, were less likely to be treated by connected hospitals.ConclusionsWhile the majority of shared patients received care from connected hospitals, remaining gaps could be filled by connecting HIE networks to each other and by incentivizing certain types of hospitals that may not participate because of competitive concerns.

Proteasomes critically regulate proteostasis via protein degradation. Proteasomes are multi-subunit complexes composed of the 20S proteolytic core particle (20S CP) that, in association with one or two 19S regulatory particles (19S RPs), generates the 26S proteasome, which is the major proteasomal complex in cells. Native gel protocols are used to investigate the 26S/20S ratio. However, a simple method for detecting these proteasome complexes in cells is missing. To this end, using CRISPR technology, we YFP-tagged the endogenous PSMB6 (β1) gene, a 20S CP subunit, and co-tagged endogenous PSMD6 (Rpn7), a 19S RP subunit, with the mScarlet fluorescent protein. We observed the colocalization of the YFP and mScarlet fluorescent proteins in the cells, with higher nuclear accumulation. Nuclear proteasomal granules are formed under osmotic stress, and all were positive for YFP and mScarlet. Previously, we have reported that PSMD1 knockdown, one of the 19 RP subunits, gives rise to a high level of “free” 20S CPs. Intriguingly, under this condition, the 20S-YFP remained nuclear, whereas the PSMD6-mScarlet was mostly in cytoplasm, demonstrating the distinct subcellular distribution of uncapped 20S CPs. Lately, we have shown that the PSMA3 (α7) C-terminus, a 20S CP subunit, binds multiple intrinsically disordered proteins (IDPs). Remarkably, the truncation of the PSMA3 C-terminus is phenotypically reminiscent of PSMD1 knockdown. These data suggest that the PSMA3 C-terminal region is critical for 26S proteasome integrity.

Proteasomes critically regulate proteostasis via protein degradation. Proteasomes are multisubunit complexes composed of the 20S proteolytic core particle (20S CP) that, in association with one or two 19S regulatory particles (19S RPs), generate the 26S proteasome. 26S is the major proteasomal complex in the cells. Native gel protocols are used to investigate the 26S/20S ratio. However, a simple method for detecting these proteasome complexes in the cells is missing. To this end, using CRISPR technology, we YFP tagged the endogenous PSMB6 (b1) gene, a 20S CP subunit, and co-tagged endogenous PSMD6 (Rpn7), a 19S RP subunit, with mScarlet fluorescent protein. We observed colocalization of YFP and mScarlet fluorescent proteins in the cells, with higher nuclear accumulation. Nuclear proteasomal granules are formed under osmotic stress, and all were positive for YFP and mScarlet. Previously we have reported that PSMD1 knockdown, one of the 19 RP subunits, gives rise to a high level of “free” 20S CP. Intriguingly, under this condition, the 20S-YFP remained nuclear, whereas the PSMD6-mScarlet is mostly in cytoplasm, demonstrating the distinct subcellular distribution of uncapped 20S CP. Lately, we have shown that the PSMA3 (a7) C-termininus, a 20S CP subunit, binds multiple intrinsically disordered proteins (IDPs). Remarkably, truncation of the PSMA3 C-terminus is phenotypically reminiscent of PSMD1 knockdown. These data suggest the PSMA3 C-terminal region is critical for the 26S proteasome integrity.

INTRODUCTION: The inability to achieve high COVID-19 vaccination rates can continue to have serious harm to our communities. Vaccine hesitancy is a major barrier towards high vaccination rates. We evaluated the relationship between COVID-19 vaccine uptake and vaccine hesitancy, and then examined whether community factors were associated with COVID-19 vaccine uptake and hesitancy. METHODS: We constructed and evaluated a cross-sectional, county-level dataset that included the levels of vaccination uptake and vaccine hesitancy, and population characteristics based on those included in the CDCs Social Vulnerability Index. RESULTS: Across 3142 US counties, vaccine hesitancy was significantly and negatively correlated with vaccine uptake rates(r=-0.06, p-value

Computable social risk factor phenotypes derived from routinely collected structured electronic health record (EHR) or health information exchange (HIE) data may represent a feasible and robust approach to measuring social factors. This study convened an expert panel to identify and assess the quality of individual EHR and HIE structured data elements that could be used as components in future computable social risk factor phenotypes.Technical expert panel.A 2-round Delphi technique included 17 experts with an in-depth knowledge of available EHR and/or HIE data. The first-round identification sessions followed a nominal group approach to generate candidate data elements that may relate to socioeconomics, cultural context, social relationships, and community context. In the second-round survey, panelists rated each data element according to overall data quality and likelihood of systematic differences in quality across populations (ie, bias).Panelists identified a total of 89 structured data elements. About half of the data elements (n = 45) were related to socioeconomic characteristics. The panelists identified a diverse set of data elements. Elements used in reimbursement-related processes were generally rated as higher quality. Panelists noted that several data elements may be subject to implicit bias or reflect biased systems of care, which may limit their utility in measuring social factors.Routinely collected structured data within EHR and HIE systems may reflect patient social risk factors. Identifying and assessing available data elements serves as a foundational step toward developing future computable social factor phenotypes.

This study evaluates the adoption of clinician billing for patient portal messages as e-visits, prompted by significant increases in patient messaging after the onset of the COVID-19 pandemic.

The adoption of electronic health records (EHRs) and digitization of health data over the past decade is ushering in the next generation of digital health tools that leverage artificial intelligence (AI) to improve varied aspects of health system performance. The decade ahead is therefore shaping up to be one in which digital health becomes even more at the forefront of health care delivery - demanding the time, attention, and resources of health care leaders and frontline staff, and becoming inextricably linked with all dimensions of health care delivery. In this chapter, we look back and look ahead. There are substantive lessons learned from the first era of large-scale adoption of enterprise EHRs and ongoing challenges that organizations are wrestling with - particularly related to the tension between standardization and flexibility/customization of EHR systems and the processes they support. Managing this tension during efforts to implement and optimize enterprise systems is perhaps the core challenge of the past decade, and one that has impeded consistent realization of value from initial EHR investments. We describe these challenges, how they manifest, and organizational strategies to address them, with a specific focus on alignment with broader value-based care transformation. We then look ahead to the AI wave - the massive number of applications of AI to health care delivery, the expected benefits, the risks and challenges, and approaches that health systems can consider to realize the benefits while avoiding the risks.

This cohort study examines changes in physician electronic health record (EHR) documentation time before and after changes in Centers for Medicare & Medicaid evaluation and management requirements.

ObjectiveTo identify organizational complementarities of adoption and use of electronic health records (EHRs) and assess what organizational strategies were associated with more advanced EHR use.Data sourcesPrimary survey data of US hospitals combined with secondary data from the American Hospital Association Annual Survey and IT Supplement.Study designIn this cross-sectional study, we describe hospital organizational practices around EHR adoption and use and identify how these practices coalesce into distinct strategies. We then assess the association between those organizational strategies and adoption of advanced EHR functions.Data collectionPrimary data collection consisted of surveys sent to 797 US acute care hospitals in 2018-2019, with 451 complete respondents.Principal findingsThere was significant variation in hospital organizational practices for EHR adoption and use. Factor analysis identified practices in three domains: leadership engagement, human capital, and systems integration. Hospitals in the top quartile of the leadership engagement factor were 14 percentage points more likely to have adopted patient engagement EHR functions (P=0.01) while hospitals in the top quartile of human capital were 14 percentage points less likely to have adopted these functions (P=0.02). Hospitals in the top quartile of systems integration were 12 percentage points more likely to have adopted patient engagement functions (P=0.02) and 14 percentage points more likely to have adopted EHR data analytics functions (P=0.02).ConclusionsOur findings suggest that specific organizational strategies are associated with more advanced EHR adoption. Hospital leaders interested in realizing more value from their EHR investment may find it useful to know that there is an association between adoption of more advanced EHR functions, and engaging senior leadership as well as building connectivity between clinical and administrative systems.

Objective Recent policy making aims to prevent health systems, lectronic health record (EHR) vendors, and others from blocking the electronic sharing of patient data necessary for clinical care. We sought to assess the prevalence of information blocking prior to enforcement of these rules. Materials and Methods We conducted a national survey of health information exchange organizations (HIEs) to measure the prevalence of information blocking behaviors observed by these third-party entities. Eighty-nine of 106 HIEs (84%) meeting the inclusion criteria responded. Results The majority (55%) of HIEs reported that EHR vendors at least sometimes engage in information blocking, while 30% of HIEs reported the same for health systems. The most common type of information blocking behavior EHR vendors engaged in was setting unreasonably high prices, which 42% of HIEs reported routinely observing. The most common type of information blocking behavior health systems engaged in was refusing to share information, which 14% of HIEs reported routinely observing. Reported levels of vendor information blocking was correlated with regional competition among vendors and information blocking was concentrated in some geographic regions. Discussion Our findings are consistent with early reports, revealing persistently high levels of information blocking and important variation by actor, type of behavior, and geography. These trends reflect the observations and experiences of HIEs and their potential biases. Nevertheless, these data serve as a baseline against which to measure the impact of new regulations and to inform policy makers about the most common types of information blocking behaviors. Conclusion Enforcement aimed at reducing information blocking should consider variation in prevalence and how to most effectively target efforts.

A discussion and debate on the American Medical Informatics Association’s (AMIA) Ethical, Legal, and Social Issues (ELSI) Working Group listserv in 2021 raised important issues related to a forthcoming conference in Texas. Texas had recently enacted a restrictive abortion law and restricted voting rights. Several AMIA members advocated for a boycott of the state and the scheduled conference. The discussion led the AMIA Board of Directors to request that the organization’s Ethics Committee provide general guidance for principle-based venue selection. This document recommends overarching principles for the venue selection for future AMIA events and conferences. Discussions by the AMIA Board, the Ethics Committee, and the ELSI Working Group informed these recommendations, and this document on guiding principles was approved by the AMIA Board of Directors in April 2022.

Vascular smooth muscle cells (VSMCs) can switch from their contractile state to a synthetic phenotype resulting in high migratory and proliferative capacity and driving atherosclerotic lesion formation. The cysteine-rich LIM-only protein 4 (CRP4) reportedly modulates VSM-like transcriptional signatures, which are perturbed in VSMCs undergoing phenotypic switching. Thus, we hypothesized that CRP4 contributes to adverse VSMC behaviours and thereby to atherogenesis in vivo. The atherogenic properties of CRP4 were investigated in plaque-prone apolipoprotein E (ApoE) and CRP4 double-knockout (dKO) as well as ApoE-deficient CRP4 wildtype mice. dKO mice exhibited lower plaque numbers and lesion areas as well as a reduced content of α-smooth muscle actin positive cells in the lesion area, while lesion-associated cell proliferation was elevated in vessels lacking CRP4. Reduced plaque volumes in dKO correlated with significantly less intra-plaque oxidized low-density lipoprotein (oxLDL), presumably due to upregulation of the antioxidant factor peroxiredoxin-4 (PRDX4). This study identifies CRP4 as a novel pro-atherogenic factor that facilitates plaque oxLDL deposition and identifies the invasion of atherosclerotic lesions by VSMCs as important determinants of plaque vulnerability. Thus, targeting of VSMC CRP4 should be considered in plaque-stabilizing pharmacological strategies.

Objective To measure US hospitals’ adoption of electronic health record (EHR) functions that support care for older adults, focusing on structured documentation of the 4Ms (What Matters, Medication, Mentation, and Mobility) and electronic health information exchange/communication with patients, caregivers, and long-term care providers. Materials and Methods In an online survey of a national, random sample of 797 US acute-care hospitals in 2018–2019, 479 (60.1%) responded. We calculated nationally representative measures of the percentages of hospitals with EHRs that include structured documentation of the 4Ms and exchange/communications functions. Results Structured EHR documentation of the 4Ms was fully implemented in at least 1 unit in 64.0% of hospitals and across all units in 41.5% of hospitals. Of the 4Ms, structured documentation was the highest for medications (91.3% in at least 1 unit) and the lowest for mentation (70.3% in at least 1 unit). All exchange/communication functions had been implemented in at least 1 unit in 16.2% of facilities and across all units in 7.6% of hospitals. Less than half of the hospitals had an EHR portal for long-term care facilities to access hospital information (45.4% in at least 1 unit), sent information electronically to long-term care facilities (44.6%), and had training for adults/caregivers on the patient portal (32.1%). Discussion Despite significant national investment in EHRs, hospital EHRs do not yet include key documentation, exchange, and communication functions needed to support evidence-based care for the older adults who comprise the majority of the inpatient population. Additional policy efforts are likely needed to promote the expansion of EHR capabilities into these high-value domains. Conclusions US acute-care hospital EHRs are lacking key functions that support care for older adults.

Clinical workflow is the enactment of a series of steps to perform a clinical activity. The transition from paper to electronic health records (EHRs) over the past decade has been characterized by profound challenges supporting clinical workflow, impeding frontline clinicians' ability to deliver safe, efficient, and effective care. In response, there has been substantial effort to study clinical workflow as well as workarounds-exceptions to routine workflow-in order to identify opportunities for improvement. This article describes predominant methods of studying workflow and workarounds and provides examples of the applications of these methods along with the resulting insights. Challenges to studying workflow and workarounds are described, and recommendations for how to approach such studies are given. Although there is not yet a set of standard approaches, this article helps advance workflow research that ultimately serves to inform how to coevolve the design of EHR systems and organizational decisions about processes, roles, and responsibilities in order to support clinical workflow that more consistently delivers on the potential benefits of a digitized health care system.

The 3',5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase type I (cGKI aka PKGI) is a major cardiac effector acting downstream of nitric oxide (NO)-sensitive soluble guanylyl cyclase and natriuretic peptides (NPs), which signal through transmembrane guanylyl cyclases. Consistent with the wide distribution of the cGMP-generating guanylyl cyclases, cGKI, which usually elicits its cellular effects by direct phosphorylation of its targets, is present in multiple cardiac cell types including cardiomyocytes (CMs). Although numerous targets of cGMP/cGKI in heart were identified in the past, neither their exact patho-/physiological functions nor cell-type specific roles are clear. Herein, we inform about the current knowledge on the signal transduction downstream of CM cGKI. We believe that better insights into the specific actions of cGMP and cGKI in these cells will help to guide future studies in the search for predictive biomarkers for the response to pharmacological cGMP pathway modulation. In addition, targets downstream of cGMP/cGKI may be exploited for refined and optimized diagnostic and therapeutic strategies in different types of heart disease and their causes. Importantly, key functions of these proteins and particularly sites of regulatory phosphorylation by cGKI should, at least in principle, remain intact, although upstream signaling through the second messenger cGMP is impaired or dysregulated in a stressed or diseased heart state.

ObjectiveThere has been substantial growth in eHealth over the past decade, driven by expectations of improved healthcare system performance. Despite substantial eHealth investment, little is known about the monitoring and evaluation strategies for gauging progress in eHealth availability and use. This scoping review aims to map the existing literature and depict the predominant approaches and methodological recommendations to national and regional monitoring and evaluation of eHealth availability and use, to advance national strategies for monitoring and evaluating eHealth.MethodsPeer-reviewed and grey literature on monitoring and evaluation of eHealth availability and use published between January 1, 2009, and March 11, 2019, were eligible for inclusion. A total of 2354 publications were identified and 36 publications were included after full-text review. Data on publication type (eg, empirical research), country, level (national or regional), publication year, method (eg, survey), and domain (eg, provider-centric electronic record) were charted.ResultsThe majority of publications monitored availability alone or applied a combination of availability and use measures. Surveys were the most common data collection method (used in 86% of the publications). Organization for Economic Co-operation and Development (OECD), European Commission, Canada Health Infoway, and World Health Organization (WHO) have developed comprehensive eHealth monitoring and evaluation methodology recommendations.DiscussionEstablishing continuous national eHealth monitoring and evaluation, based on international approaches and recommendations, could improve the ability for cross-country benchmarking and learning. This scoping review provides an overview of the predominant approaches to and recommendations for national and regional monitoring and evaluation of eHealth. It thereby provides a starting point for developing national eHealth monitoring strategies.

Despite expectations that Medicare accountable care organizations (ACOs) would curb health care spending, their effect has been modest. One possible explanation is that ACOs' inability to prohibit out-of-network care limits their control over spending. To examine this possibility, we examined the association between out-of-network care and per beneficiary spending using national Medicare data for 2012-15. While there was no association between out-of-network specialty care and ACO spending, each percentage-point increase in receipt of out-of-network primary care was associated with an increase of $10.79 in quarterly total ACO spending per beneficiary. When we broke down total spending by place of service, we found that out-of-network primary care was associated with higher spending in outpatient, skilled nursing facility, and emergency department settings, but not inpatient settings. Our findings suggest an opportunity for the Medicare program to realize substantial savings, if policy makers developed explicit incentives for beneficiaries to seek more of their primary care within network.

Objective To assess longitudinal primary care organization participation patterns in large-scale reform programs and identify organizational characteristics associated with multiprogram participation. Data sources Secondary data analysis of national program participation data over an eight-year period (2009-2016). Study design We conducted a retrospective, observational study by creating a unique set of data linkages (including Medicare and Medicaid Meaningful Use and Medicare Shared Savings Program Accountable Care Organization (MSSP ACO) participation from CMS, Patient-Centered Medical Home (PCMH) participation from the National Committee for Quality Assurance, and organizational characteristics) to measure longitudinal participation and identify what types of organizations participate in one or more of these reform programs. We used multivariate models to identify organizational characteristics that differentiate those that participate in none, one, or two-to-three programs. Data extraction methods We used Medicare claims to identify organizations that delivered primary care services (n = 56 ,287) and then linked organizations to program participation data and characteristics. Principal findings No program achieved more than 50% participation across the 56,287 organizations in a given year, and participation levels flattened or decreased in later years. 36% of organizations did not participate in any program over the eight-year study period; 50% participated in one; 13% in two; and 1% in all three. 14.31% of organizations participated in five or more years of Meaningful Use while 3.84% of organizations participated in five years of the MSSP ACO Program and 0.64% participated in at least five years of PCMH. Larger organizations, those with younger providers, those with more primary care providers, and those with larger Medicare patient panels were more likely to participate in more programs. Conclusions and relevance Primary care transformation via use of voluntary programs, each with their own participation requirements and approach to incentives, has failed to broadly engage primary care organizations. Those that have chosen to participate in multiple programs are likely those already providing high-quality care.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the COVID-19 pandemic. More than 274 million individuals have suffered from COVID-19 and over five million people have died from this disease so far. Therefore, there is an urgent need for therapeutic drugs. Repurposing FDA approved drugs should be favored since evaluation of safety and efficacy of de-novo drug design are both costly and time consuming. We report that imatinib, an Abl tyrosine kinase inhibitor, robustly decreases SARS-CoV-2 infection and uncover a mechanism of action. We show that imatinib inhibits the infection of SARS-CoV-2 and its surrogate lentivector pseudotype. In latter, imatinib inhibited both routes of viral entry, endocytosis and membrane-fusion. We utilized a system to quantify in real-time cell–cell membrane fusion mediated by the SARS-CoV-2 surface protein, Spike, and its receptor, hACE2, to demonstrate that imatinib inhibits this process in an Abl1 and Abl2 independent manner. Furthermore, cellular thermal shift assay revealed a direct imatinib-Spike interaction that affects Spike susceptibility to trypsin digest. Collectively, our data suggest that imatinib inhibits Spike mediated viral entry by an off-target mechanism. These findings mark imatinib as a promising therapeutic drug in inhibiting the early steps of SARS-CoV-2 infection.