eScholarship@UMassChan Repository at UMass Chan Medical School

eScholarship@UMassChan

Sherman Center building at UMass Chan Medical School at night

eScholarship@UMassChan is a digital repository for UMass Chan Medical School's research and scholarship, including journal articles, theses, datasets and more. We welcome submissions from our faculty, staff, and students. eScholarship@UMassChan is a service of the Lamar Soutter Library, Worcester, MA, USA. See also our open access journal publishing services.

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  • Celebrating and Congratulations!

    Silk, Hugh (2024-03-21)
    Introduction: This week I am celebrating, along with my colleagues, our very successful match into family medicine (and to our residencies)! With 14.02% of UMass Chan students matching into Family Medicine, we exceeded the national average of 12.7% (per AAFP). Family Medicine Proud! This quote from Dr. Victor Johnson, known as the founding father of the College of General Practitioners now the College of Family Physicians in Canada, summarizes their future impact. "I became convinced that the medical profession would be saved not by its organization but by the sum total of the common sense and humanity of its individual practicing members. General practitioners... are the doctors closest to [the] people. They heal more of the broken hearted, repair more of the injured and deprived, and live with the poor and dying who are without influence and hope. As Family Physicians, you are ideally positioned in the health care system to understand patients and their family and community context, and to provide for them a deep connection, compassion, and care." The picture below says it best. These individuals are way more than a statistic. They will make us proud in the way Victor Johnson wanted family doctors to be. Congratulations to these future family physicians and to all who taught, challenged, mentored, coached, consoled, and encouraged them. Take a moment and congratulate yourselves too! Be well.
  • Over Fartsgrensen

    Gracey, Kristina (2024-03-14)
    Introduction: This week I am grateful to Kristina Gracey, faculty at Barre Family Health Center, for her essay that is both personal and informative. She is an avid and successful runner. Which can be dangerous. She has been thinking about this element of risk and adds a public health perspective to her reflection that I personally admire. Food for thought for possible collective advocacy by us all on this topic.
  • Sampling of healthcare professionals' perspective on point-of-care technologies from 2019-2021: A survey of benefits, concerns, and development

    Orwig, Taylor; Sutaria, Shiv; Wang, Ziyue; Howard-Wilson, Sakeina; Dunlap, Denise; Lilly, Craig M; Buchholz, Bryan; McManus, David D; Hafer, Nathaniel (2024-03-08)
    Point-of-care technology (POCT) plays a vital role in modern healthcare by providing a fast diagnosis, improving patient management, and extending healthcare access to remote and resource-limited areas. The objective of this study was to understand how healthcare professionals in the United States perceived POCTs during 2019-2021 to assess the decision-making process of implementing these newer technologies into everyday practice. A 5-point Likert scale survey was sent to respondents to evaluate their perceptions of benefits, concerns, characteristics, and development of point-of-care technologies. The 2021 survey was distributed November 1st, 2021- February 15th, 2022, with a total of 168 independent survey responses received. Of the respondents, 59% identified as male, 73% were white, and 48% have been in practice for over 20 years. The results showed that most agreed that POCTs improve patient management (94%) and improve clinician confidence in decision making (92%). Healthcare professionals were most concerned with potentially not being reimbursed for the cost of the POCT (37%). When asked to rank the top 3 important characteristics of POCT, respondents chose accuracy, ease of use, and availability. It is important to note this survey was conducted during the COVID-19 pandemic. To achieve an even greater representation of healthcare professionals' point of view on POCTs, further work to obtain responses from a larger, more diverse population of providers is needed.
  • Photos of Meaningful Things and Places

    Penumetcha, Venkata "Sai Sri"; Isaac, Tamika; Coderre, Danielle; Silk, Hugh (2024-03-07)
    Introduction: This week I have a visual treat. Last week Sara Shields and I had a session with the PGY1s on the topic of medical humanities and one of the prompts was to go into the hospital and return with a photo of something that is meaningful to you - can be a piece, a thing, a person. The discussion that ensued from these photos was wonderful! I am sharing some of the photos here for you with their title. Enjoy.
  • Introducing Telomere-Dysfunction Induced Cellular Senescence in iPSC-Based Modeling Of Neurodegenerative Diseases

    Neherin, Kashfia (2024-03-06)
    Investigation of disease-associated cellular changes in vitro has leaped forward significantly with the innovation of induced pluripotent stem cell (iPSC) technology. However, resetting the epigenetic landscape and aging clock during reprogramming results in iPSC-differentiated cells resembling fetal cell types instead of adult or aged cells. The lack of cellular aging in iPSC-based models presents a significant drawback in the investigation of age-associated diseases such as Alzheimer’s disease. My thesis aims to introduce proper cellular aging to improve iPSC-based modeling of neurodegeneration. Toward this goal, I created an inducible system to trigger senescence in iPSC-based cell models, as recent studies showed senescence playing a crucial role in aging and neurodegeneration. I utilized CRISPR-interference (CRISPRi) to suppress telomere repeat factor 2 (TERF2), a significant component of the telomere-protecting Shelterin complex. I demonstrated that suppression of TERF2 in iPSCs robustly activated DNA damage response (DDR), p53/p21 signaling, and cellular senescence in an inducible and synchronized manner. The inducible approach allows temporal control of senescence activation throughout differentiation from iPSCs to desired cell types. I applied the CRISPRi-TERF2 approach to iPSC-differentiated neural progenitor cells (NPCs) and showed that suppression of TERF2 efficiently activated DDR, p53/p21 signaling, and cellular senescence in differentiated NPCs. This inducible model of cellular senescence generated in this study will enable the investigation of cellular senescence using isogenic comparisons in the progression of age-associated neurodegeneration and improve disease modeling with a proper cellular aging context to facilitate drug discovery.
  • UMCCTS Newsletter, March 2024

    UMass Center for Clinical and Translational Science (2024-03-01)
    This is the March 2024 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
  • Adjustment for Renal Function Improves the Prognostic Performance of Urinary Thromboxane Metabolites

    Barton, Bruce A; Kronsberg, Shari S; Hariri, Essa; Vasan, Ramachandran S; Rade, Grace A; Xanthakis, Vanessa; Kickler, Thomas S; Rade, Jeffrey J (2024-02-28)
    Background: Systemic thromboxane A2 generation, assessed by quantifying the concentration of stable thromboxane B2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. Methods: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study. Cutpoints were determined for TXB2-M and TXB2-M/eGFR using log-rank statistics and used to assess mortality risk by Cox proportional hazard modeling and restricted mean survival time. Multivariable models were compared using the Akaike Information Criterion (AIC). A cohort of 105 aspirin users with heart failure was used for external validation. Results: Optimized cutpoints of TXB2-M were 1291 and 5609 pg/mg creatinine and of TXB2-M/eGFR were 16.6 and 62.1 filtered prostanoid units (defined as pg·min/creatinine·mL·1.73 m2), for aspirin users and nonusers, respectively. TXB2-M/eGFR cutpoints provided more robust all-cause mortality risk discrimination than TXB2-M cutpoints, with a larger unadjusted hazard ratio (2.88 vs 2.16, AIC P < 0.0001) and greater differences in restricted mean survival time between exposure groups (1.46 vs 1.10 years), findings that were confirmed in the external validation cohort of aspirin users. TXB2-M/eGFR cutpoints also provided better cardiovascular/stroke mortality risk discrimination than TXB2-M cutpoints (unadjusted hazard ratio 3.31 vs 2.13, AIC P < 0.0001). Conclusion: Adjustment for eGFR strengthens the association of urinary TXB2-M with long-term mortality risk irrespective of aspirin use.
  • Adulting Shorts: Let’s Talk About Workplace Accommodations

    Seward, Hannah (2024-02-27)
    Work can be hard! If you have a mental health condition, you might need to ask for an accommodation at work. An accommodation is a change to the way your job is done to allow you to do your job well when you have a disability. This comic by the NIDILRR-funded Learning & Working RRTC shares some real-world experiences young adults with lived experience of mental health conditions when working. For more information about requesting accommodations at work, please read our Accommodations at Work tip sheet.
  • Fleischner Society: Glossary of Terms for Thoracic Imaging

    Bankier, Alexander A; MacMahon, Heber; Colby, Thomas; Gevenois, Pierre Alain; Goo, Jin Mo; Leung, Ann N C; Lynch, David A; Schaefer-Prokop, Cornelia M; Tomiyama, Noriyuki; Travis, William D; et al. (2024-02-27)
    Members of the Fleischner Society have compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984, 1996, and 2008, respectively. The impetus to update the previous version arose from multiple considerations. These include an awareness that new terms and concepts have emerged, others have become obsolete, and the usage of some terms has either changed or become inconsistent to a degree that warranted a new definition. This latest glossary is focused on terms of clinical importance and on those whose meaning may be perceived as vague or ambiguous. As with previous versions, the aim of the present glossary is to establish standardization of terminology for thoracic radiology and, thereby, to facilitate communications between radiologists and clinicians. Moreover, the present glossary aims to contribute to a more stringent use of terminology, increasingly required for structured reporting and accurate searches in large databases. Compared with the previous version, the number of images (chest radiography and CT) in the current version has substantially increased. The authors hope that this will enhance its educational and practical value. All definitions and images are hyperlinked throughout the text. Click on each figure callout to view corresponding image. © RSNA, 2024 Supplemental material is available for this article. See also the editorials by Bhalla and Powell in this issue.
  • Modeling neurodevelopmental disorder-associated human AGO1 mutations in Caenorhabditis elegans Argonaute alg-1

    Duan, Ye; Li, Li; Panzade, Ganesh Prabhakar; Piton, Amélie; Zinovyeva, Anna; Ambros, Victor R. (2024-02-27)
    MicroRNAs (miRNA) associate with Argonaute (AGO) proteins and repress gene expression by base pairing to sequences in the 3' untranslated regions of target genes. De novo coding variants in the human AGO genes AGO1 and AGO2 cause neurodevelopmental disorders (NDD) with intellectual disability, referred to as Argonaute syndromes. Most of the altered amino acids are conserved between the miRNA-associated AGO in Homo sapiens and Caenorhabditis elegans, suggesting that the human mutations could disrupt conserved functions in miRNA biogenesis or activity. We genetically modeled four human AGO1 mutations in C. elegans by introducing identical mutations into the C. elegans AGO1 homologous gene, alg-1. These alg-1 NDD mutations cause phenotypes in C. elegans indicative of disrupted miRNA processing, miRISC (miRNA silencing complex) formation, and/or target repression. We show that the alg-1 NDD mutations are antimorphic, causing developmental and molecular phenotypes stronger than those of alg-1 null mutants, likely by sequestrating functional miRISC components into non-functional complexes. The alg-1 NDD mutations cause allele-specific disruptions in mature miRNA profiles, accompanied by perturbation of downstream gene expression, including altered translational efficiency and/or messenger RNA abundance. The perturbed genes include those with human orthologs whose dysfunction is associated with NDD. These cross-clade genetic studies illuminate fundamental AGO functions and provide insights into the conservation of miRNA-mediated post-transcriptional regulatory mechanisms.
  • Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study

    Dmytriw, Adam A; Musmar, Basel; Salim, Hamza; Ghozy, Sherief; Siegler, James E; Kobeissi, Hassan; Shaikh, Hamza; Khalife, Jane; Abdalkader, Mohamad; Klein, Piers; et al. (2024-02-26)
    Background: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. Methods: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. Results: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). Conclusion: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.
  • The Greatest Health Care System in the World

    Adelstein, Pamela (2024-02-22)
    Introduction: This week I am sharing with you another piece from Pam Adelstein, a former resident of the Family Health Center of Worcester, and now the Medical Director at Fenway Health. Her piece was written as a reflection on the prompt “cold”. As you can see, she writes about way too many people being left out in the cold in our healthcare system.
  • Racial and Ethnic Disparities in Use of Colorectal Cancer Screening Among Adults With Chronic Medical Conditions: BRFSS 2012-2020

    Castañeda-Avila, Maira A; Tisminetzky, Mayra; Oyinbo, Atinuke G; Lapane, Kate L (2024-02-22)
    Introduction: People with chronic conditions and people with colorectal cancer (CRC) may share common risk factors; thus, CRC screening is important for people with chronic conditions. We examined racial and ethnic differences in the use of CRC screening among people with various numbers of chronic conditions. Methods: We included data on adult respondents aged 50 to 75 years from the Behavioral Risk Factor Surveillance System in 2012 through 2020. We categorized counts of 9 conditions as 0, 1, 2, 3, and ≥4. We classified self-reported CRC screening status as up to date or not. We used Poisson models to estimate adjusted prevalence ratios (APRs) among the different counts of chronic conditions in 4 racial and ethnic groups: Hispanic adults with limited English proficiency (LEP), Hispanic adults without LEP, non-Hispanic Black adults, and non-Hispanic White adults. Results: Overall, 66.5% of respondents were up to date with CRC screening. The prevalence of being up to date increased with the number of chronic conditions. We found disparities among racial and ethnic groups. Hispanic respondents with LEP had lower rates than non-Hispanic White adults of being up to date with CRC screening across all counts of chronic conditions (APR for 0 conditions = 0.67; 95% CI, 0.64-0.71; APR for ≥4 conditions = 0.85; 95% CI, 0.79-0.91). Hispanic respondents without LEP with 0, 1, or 2 conditions were less likely than non-Hispanic White respondents to be up to date with CRC screening. We found no significant differences between non-Hispanic Black and non-Hispanic White respondents. Conclusion: We found disparities among Hispanic BRFSS respondents with LEP, who had lower rates than non-Hispanic White respondents of being up to date with CRC screening, regardless of the number of chronic conditions. Tailored interventions are needed to address these disparities and improve screening rates, particularly among Hispanic people.
  • A novel swine model of selective middle meningeal artery catheterization and embolization

    Mokin, Maxim; Pionessa, Donald; Koenigsknecht, Carmon; Gutierrez, Liza; Setlur Nagesh, Swetadri Vasan; Meess Tuttle, Karen M; Spengler, Mike; Akkad, Yousef; Vakharia, Kunal; Shapiro, Maksim; et al. (2024-02-22)
    Background: Middle meningeal artery (MMA) embolization is a promising intervention as a stand-alone or adjunct treatment to surgery in patients with chronic subdural hematomas. There are currently no large animal models for selective access and embolization of the MMA for preclinical evaluation of this endovascular modality. Our objective was to introduce a novel in vivo model of selective MMA embolization in swine. Methods: Diagnostic cerebral angiography with selective microcatheter catheterization into the MMA was performed under general anesthesia in five swine. Anatomical variants in arterial meningeal supply were examined. In two animals, subsequent embolization of the MMA with a liquid embolic agent (Onyx-18) was performed, followed by brain tissue harvest and histological analysis. Results: The MMA was consistently localized as a branch of the internal maxillary artery just distal to the origin of the ascending pharyngeal artery. Additional meningeal supply was observed from the external ophthalmic artery, although not present consistently. MMA embolization with Onyx was technically successful and feasible. Histological analysis showed Onyx material within the MMA lumen. Conclusions: Microcatheter access into the MMA in swine with liquid embolic agent delivery represents a reproducible model of MMA embolization. Anatomical variations in the distribution of arterial supply to the meninges exist. This model has a potential application for comparing therapeutic effects of various embolic agents in a preclinical setting that closely resembles the MMA embolization procedure in humans.
  • Persistent False Positive Covid-19 Rapid Antigen Tests

    Herbert, Carly; McManus, David D; Soni, Apurv (2024-02-22)
    Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially. The percentage of rapid antigen tests with false positive results is reported to be less than 1%. However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders.
  • Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation

    Wang, Maud; Henkes, Hans; Ghozy, Sherief; Siegler, James E; Shaikh, Hamza; Khalife, Jane; Abdalkader, Mohamad; Klein, Piers; Nguyen, Thanh N; Heit, Jeremy J; et al. (2024-02-21)
    Purpose: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. Methods: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. Results: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). Conclusion: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.
  • Auto-segmentation of Adult-Type Diffuse Gliomas: Comparison of Transfer Learning-Based Convolutional Neural Network Model vs. Radiologists

    Wan, Qi; Kim, Jisoo; Lindsay, Clifford; Chen, Xin; Li, Jing; Iorgulescu, J Bryan; Huang, Raymond Y; Zhang, Chenxi; Reardon, David; Young, Geoffrey S; et al. (2024-02-21)
    Segmentation of glioma is crucial for quantitative brain tumor assessment, to guide therapeutic research and clinical management, but very time-consuming. Fully automated tools for the segmentation of multi-sequence MRI are needed. We developed and pretrained a deep learning (DL) model using publicly available datasets A (n = 210) and B (n = 369) containing FLAIR, T2WI, and contrast-enhanced (CE)-T1WI. This was then fine-tuned with our institutional dataset (n = 197) containing ADC, T2WI, and CE-T1WI, manually annotated by radiologists, and split into training (n = 100) and testing (n = 97) sets. The Dice similarity coefficient (DSC) was used to compare model outputs and manual labels. A third independent radiologist assessed segmentation quality on a semi-quantitative 5-scale score. Differences in DSC between new and recurrent gliomas, and between uni or multifocal gliomas were analyzed using the Mann-Whitney test. Semi-quantitative analyses were compared using the chi-square test. We found that there was good agreement between segmentations from the fine-tuned DL model and ground truth manual segmentations (median DSC: 0.729, std-dev: 0.134). DSC was higher for newly diagnosed (0.807) than recurrent (0.698) (p < 0.001), and higher for unifocal (0.747) than multi-focal (0.613) cases (p = 0.001). Semi-quantitative scores of DL and manual segmentation were not significantly different (mean: 3.567 vs. 3.639; 93.8% vs. 97.9% scoring ≥ 3, p = 0.107). In conclusion, the proposed transfer learning DL performed similarly to human radiologists in glioma segmentation on both structural and ADC sequences. Further improvement in segmenting challenging postoperative and multifocal glioma cases is needed.
  • 2024 Gold Humanism Summit Art Gallery

    Silk, Hugh (2024-02-15)
    Introduction: This week I do not have a local piece to share, per se. However, I am sending you all to explore the 2024 Gold Humanism Summit Art Gallery, which showcases artwork that reflects experiences, creativity and insights from clinicians, trainees, patients, caregivers, and members of the healthcare community. I hope you enjoy this collection of visual art, video, performance, song, poetry, narrative writing, pottery, and more. The entries are from across the country. Represented from UMass are Jennifer Sohn and myself. Jennifer, (who worked with me during her LPP,) did a lovely drawing entitled, "the same on the inside". She wrote - I drew this during my second year of medical school after working for several months with local community members experiencing homelessness. I was struck by the way people tend to see unhoused individuals as intrinsically different from themselves. I wanted to emphasize that we are all human and feel joy and sadness in the same ways, no matter what our lived experiences may include. Mine is a poem entitled, Brief Advice to a Young Doctor. You can find them and many more incredible offerings here: https://www.gold-foundation.org/programs/2024-gold-humanism-summit/2024-gold-humanism-summit-art-gallery/
  • Hydroxyapatite deposition disease, an overlooked differential diagnosis in the emergency department: a case series and review of literature

    Patel, Jay; Tai, Ryan; Sereni, Christopher; Joshi, Ganesh (2024-02-15)
    Hydroxyapatite crystal deposition disease (HADD) poses diagnostic challenges in the emergency department (ED) as it may clinically present similarly to infection and other musculoskeletal conditions. Misdiagnosis often leads to unnecessary treatments and resource over-utilization. This review article provides an overview of HADD in seven patients who presented to the ED secondary to an acute presentation of this disease process. HADD is a prevalent pathology, which commonly involves the shoulder, followed by the hip, elbow, wrist, and knee. Predisposing risk factors, such as diabetes and certain genetic factors, have also been identified. Clinical history and imaging, particularly radiographs, play a vital role in diagnosing HADD, with characteristic calcification patterns observed in different stages of the disease. Conservative nonsurgical therapy is the mainstay of treatment, providing effective symptom relief in over 90% of cases. By recognizing HADD as a crucial differential diagnosis for patients with acute or chronic pain, healthcare resource utilization can be optimized, leading to improved patient care in the ED.
  • Diffusion of excellence: evaluating a system to identify, replicate, and spread promising innovative practices across the Veterans health administration

    Jackson, George L; Fix, Gemmae M; White, Brandolyn S; Cutrona, Sarah L; Reardon, Caitlin M; Damschroder, Laura J; Burns, Madison; DeLaughter, Kathryn; Opra Widerquist, Marilla A; Arasim, Maria; et al. (2024-02-13)
    Introduction: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices. Winning facilities/regions receive external facilitation to aid in replication/implementation over the course of a year. DoE staff then support diffusion of successful practices across the nationwide VHA. Methods: Organized around the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, we summarize results of an ongoing long-term mixed-methods implementation evaluation of DoE. Data sources include: Shark Tank application and bid details, tracking practice adoptions through a Diffusion Marketplace, characteristics of VHA facilities, focus groups with Shark Tank bidders, structured observations of DoE events, surveys of DoE program participants, and semi-structured interviews of national VHA program office leaders, VHA healthcare system/facility executives, practice developers, implementation teams and facilitators. Results: In the first eight Shark Tanks (2016-2022), 3,280 Shark Tank applications were submitted; 88 were designated DoE Promising Practices (i.e., practices receive facilitated replication). DoE has effectively spread practices across the VHA, with 1,440 documented instances of adoption/replication of practices across the VHA. This includes 180 adoptions/replications in facilities located in rural areas. Leadership decisions to adopt innovations are often based on big picture considerations such as constituency support and linkage to organizational goals. DoE Promising Practices that have the greatest national spread have been successfully replicated at new sites during the facilitated replication process, have close partnerships with VHA national program offices, and tend to be less expensive to implement. Two indicators of sustainment indicate that 56 of the 88 Promising Practices are still being diffused across the VHA; 56% of facilities originally replicating the practices have sustained them, even up to 6 years after the first Shark Tank. Conclusion: DoE has developed a sustainable process for the identification, replication, and spread of promising practices as part of a learning health system committed to providing equitable access to high quality care.

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