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Racism shapes the distribution of the social determinants of health (SDoH) along racial lines. Racism determines the environments in which people live, the quality of housing, and access to healthcare. Extensive research shows racism in its various forms negatively impacts health status, yet few studies and interventions seriously interrogate the role of racism in impacting health. The C2DREAM framework illuminates how exposure to racism, in multiple forms, connects to cardiovascular disease, hypertension, and obesity. The goal of the C2DREAM framework is to guide researchers to critically think about and measure the role of racism across its many levels of influence to better elucidate the ways it contributes to persistent health inequities. The conceptual framework highlights the interconnectedness between forms of racism, SDoH, and the lifecourse to provide a greater context to individual health outcomes. Utilizing this framework and critically contending with the effects of racism in its multiple and cumulative forms will lead to better research and interventions.

The hidden curriculum (HC), or implicit norms and values within a field or institution, affects faculty at all career stages. This study surveyed affiliates of a junior faculty training program (n = 12) to assess the importance of HC topics for junior faculty, mentors, and institutional leaders. For non-diverse junior faculty and their mentors, work-life balance, research logistics, and resilience were key HC topics. Coping with bias and assertive communication were emphasized for diverse junior faculty and mentors. Institutional norms and vision were essential for leaders, while networking was important for all groups. Future research should explore HC needs and potential interventions.

The benefit of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of primary sclerosing cholangitis (PSC) remains controversial. To identify predictors of jaundice resolution after ERCP and whether resolution is associated with improved patient outcomes, we conducted a retrospective cohort study of 124 patients with jaundice and PSC. These patients underwent endoscopic biliary balloon dilation and/or stent placement at an American tertiary center, with validation in a separate cohort of 102 patients from European centers. Jaundice resolved after ERCP in 52% of patients. Median follow‐up was 4.8 years. Independent predictors of jaundice resolution included older age (P = 0.048; odds ratio [OR], 1.03 for every 1‐year increase), shorter duration of jaundice (P = 0.059; OR, 0.59 for every 1‐year increase), lower Mayo Risk Score (MRS) (P = 0.025; OR, 0.58 for every 1‐point increase), and extrahepatic location of the most advanced biliary stricture (P = 0.011; OR, 3.13). A logistic regression model predicted jaundice resolution with area under the receiver operator characteristic curve of 0.67 (95% confidence interval, 0.5‐0.79) in the validation set. Independent predictors of death or transplant during follow‐up included higher MRS at the time of ERCP (P

This paper outlines the development, deployment and use, and testing of a tool for measuring and improving healthcare researcher embeddedness – i.e., being connected to and engaged with key leverage points and stakeholders in a health system. Despite the widely acknowledged importance of embeddedness for learning health systems and late-stage translational research, we were not aware of useful tools for addressing and improving embeddedness in scholar training programs. We developed the MN-LHS Embeddedness Tool covering connections to committees, working groups, leadership, and other points of contact across four domains: patients and caregivers; local practice (e.g., operations and workflows); local institutional research (e.g., research committees and agenda- or initiative-setting groups); and national (strategic connections within professional groups, conferences, etc.). We used qualitative patterns and narrative findings from 11 learning health system training program scholars to explore variation in scholar trajectories and the embeddedness tool’s usefulness in scholar professional development. Tool characteristics showed moderate evidence of construct validity; secondarily, we found significant differences in embeddedness, as a score, from baseline through program completion. The tool has demonstrated simple, practical utility in making embeddedness an explicit (rather than hidden) part of applied and learning health system researcher training, alongside emerging evidence for validity.

Abstract Introduction The learning health system (LHS) aligns science, informatics, incentives, stakeholders, and culture for continuous improvement and innovation. The Agency for Healthcare Research and Quality and the Patient‐Centered Outcomes Research Institute designed a K12 initiative to grow the number of LHS scientists. We describe approaches developed by 11 funded centers of excellence (COEs) to promote partnerships between scholars and health system leaders and to provide mentored research training. Methods Since 2018, the COEs have enlisted faculty, secured institutional resources, partnered with health systems, developed and implemented curricula, recruited scholars, and provided mentored training. Program directors for each COE provided descriptive data on program context, scholar characteristics, stakeholder engagement, scholar experiences with health system partnerships, roles following program completion, and key training challenges. Results To date, the 11 COEs have partnered with health systems to train 110 scholars. Nine (82%) programs partner with a Veterans Affairs health system and 9 (82%) partner with safety net providers. Clinically trained scholars (n = 87; 79%) include 70 physicians and 17 scholars in other clinical disciplines. Non‐clinicians (n = 29; 26%) represent diverse fields, dominated by population health sciences. Stakeholder engagement helps scholars understand health system and patient/family needs and priorities, enabling opportunities to conduct embedded research, improve outcomes, and grow skills in translating research methods and findings into practice. Challenges include supporting scholars through roadblocks that threaten to derail projects during their limited program time, ranging from delays in access to data to COVID‐19‐related impediments and shifts in organizational priorities. Conclusions Four years into this novel training program, there is evidence of scholars' accomplishments, both in traditional academic terms and in terms of moving along career trajectories that hold the potential to lead and accelerate transformational health system change. Future LHS training efforts should focus on sustainability, including organizational support for scholar activities.

Abstract Background Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process. Methods Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m2 were studied. Urinary EVs were quantified by digital flow cytometer and results expressed as EVs/ mg creatinine. Expressions of urinary proteins were measured by customized antibody array and results expressed as relative intensity. Data were analyzed by ANCOVA adjusting for sex, and biomarkers differences were considered statistically significant among groups at a false discovery rate threshold of Q

In recent years, there have been concerted efforts to better recruit, support, and retain diverse faculty, staff, and trainees in academic medicine. However, many institutions lack comprehensive and strategic plans to provide support to retain and recruit individuals from historically underrepresented groups. In this article, we itemize specific mechanisms through which institutions can support diverse individuals with the goal of improving inclusion and belonging in the workforce to better reflect the diversity of the intended patient and research participant population.

Introduction As the pandemic continues with new variants emerging, faculty and students require support with education's rapid shift to the virtual space. The Mayo Clinic Center for Clinical and Translational Science curriculum team works closely with faculty to support a smooth transition to offering graduate courses in a virtual learning environment. The aim of the present project was to explore faculty and student perceptions of these remote learning strategies to gain an understanding of the innovations required to improve future educational offerings. Methods All faculty and learners involved in nine Clinical and Translational Science courses in spring 2020 were invited to participate in a web-based questionnaire. Quantitative analysis was performed on closed-ended items, including 5-point Likert-scale questions used to assess the range of views. Qualitative free-text responses were independently analyzed for repetitive themes and summarized. Additionally, comparisons of faculty and course evaluations and student grade point averages (GPAs) from the in-person courses and their subsequent virtual course offerings were considered. Results Survey results indicated several positive impacts with moving courses into the virtual environment, including increased accessibility as well as more student-centered education. Learners joining from sites outside of the originating campus were especially grateful for the virtual classroom because they felt newly integrated within classes. Faculty and course evaluations, as well as student GPAs, remained consistent. Conclusion New COVID-19 variants continue to shift education online, and innovative ideas are required to further improve future virtual course offerings. Increased engagement is warranted, both from faculty to incorporate activities designed specifically for a virtual classroom, and from students to increase participation by activating their microphones and webcams. Greater opportunities for global involvement and connectedness arise. Finally, this project advocates for adequate eLearning staffing to support quality online education as the need for pedagogical and technical provision continues.

Abstract Background Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. Methods A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and eGFR. Results Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (eGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and eGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher eGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. Conclusion In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

As the pace of biomedical innovation rapidly evolves, there is a need to train researchers to understand regulatory science challenges associated with clinical translation. We describe a pilot course aimed at addressing this need delivered jointly through the Mayo Clinic Center for Clinical and Translational Science and the Yale-Mayo Center for Excellence in Regulatory Science and Innovation. Course design was informed by the Association for Clinical and Translational Science’s Regulatory Science Working Group’s competencies. The course used didactic, case-, and problem-based learning sessions to expose students to regulatory science concepts. Course evaluation focused on student satisfaction and learning. A total of 25 students enrolled in the first two course deliveries. Students represented several disciplines and career stages, from predoctoral to faculty. Students reported learning “an incredible amount” (7/19, 36.8%) or “a lot” (9/19, 47.4%); this was reflected in individual coursework and their course evaluations. Qualitative feedback indicated that assignments that challenged them to apply the content to their own research were appreciated. The heterogeneity of students enrolled, coupled with assessments and course evaluations, supports the statement that there is a growing need and desire for regulatory science-focused curricula. Future research will determine the long-term impact.

An amendment to this paper has been published and can be accessed via the original article.

Background: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT.Methods: Patients with PH1 enrolled in the Rare Kidney Stone Consortium PH Registry who progressed to require RRT, had ≥2 plasma oxalate (pOx) measurements 3–36 months after start of RRT, and at least one pair of pOx measurements between 6 and 18 months apart were retrospectively analyzed. Clinical, echocardiographic, and laboratory results were obtained from the Registry.Results: The 17 PH1 patients in our cohort had a mean total HD hours/week of 17.4 (SD 7.9; range 7.5–36) and a range of age of RRT start of 0.2–75.9 years. The average change in plasma oxalate (pOx) over time on RRT was −0.74 [−2.9, 1.4] μmol/L/month with the mean pOx never declining below 50 μmol/L. Over time on RRT, oxalosis progressively developed in multiple organ systems. Echocardiography performed on 13 subjects showed worsening of left ventricular global longitudinal strain correlated with pOx (p < 0.05).Conclusions: Even when a cohort of PH1 patients were treated with intensified RRT, their predialysis pOx remained above target and they developed increasing evidence of oxalosis. Echocardiographic data suggest that cardiac dysfunction could be related to elevated pOx and may worsen over time.

Background: Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. Methods: Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. Results: Bile has a unique microbiota distinguished from negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. Conclusions: We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.

AbstractPurposeThis study examined the effectiveness of a formal postdoctoral education program designed to teach skills in clinical and translational science, using scholar publication rates as a measure of research productivity.MethodParticipants included 70 clinical fellows who were admitted to a master’s or certificate training program in clinical and translational science from 1999 to 2015 and 70 matched control peers. The primary outcomes were the number of publications 5 years post-fellowship matriculation and time to publishing 15 peer-reviewed manuscripts post-matriculation.ResultsClinical and translational science program graduates published significantly more peer-reviewed manuscripts at 5 years post-matriculation (median 8 vs 5, p=0.041) and had a faster time to publication of 15 peer-reviewed manuscripts (matched hazard ratio = 2.91, p=0.002). Additionally, program graduates’ publications yielded a significantly higher average H-index (11 vs. 7, p=0.013).ConclusionThese findings support the effectiveness of formal training programs in clinical and translational science by increasing academic productivity.

Abstract Introduction: Statistical literacy is essential in clinical and translational science (CTS). Statistical competencies have been published to guide coursework design and selection for graduate students in CTS. Here, we describe common elements of graduate curricula for CTS and identify gaps in the statistical competencies. Methods: We surveyed statistics educators using e-mail solicitation sent through four professional organizations. Respondents rated the degree to which 24 educational statistical competencies were included in required and elective coursework in doctoral-level and master’s-level programs for CTS learners. We report competency results from institutions with Clinical and Translational Science Awards (CTSAs), reflecting institutions that have invested in CTS training. Results: There were 24 CTSA-funded respondents representing 13 doctoral-level programs and 23 master’s-level programs. For doctoral-level programs, competencies covered extensively in required coursework for all doctoral-level programs were basic principles of probability and hypothesis testing, understanding the implications of selecting appropriate statistical methods, and computing appropriate descriptive statistics. The only competency extensively covered in required coursework for all master’s-level programs was understanding the implications of selecting appropriate statistical methods. The least covered competencies included understanding the purpose of meta-analysis and the uses of early stopping rules in clinical trials. Competencies considered to be less fundamental and more specialized tended to be covered less frequently in graduate courses. Conclusion: While graduate courses in CTS tend to cover many statistical fundamentals, learning gaps exist, particularly for more specialized competencies. Educational material to fill these gaps is necessary for learners pursuing these activities.

Abstract Objective: To mitigate the impact of racism, sexism, and other systemic biases, it is essential for organizations to develop strategies to address their diversity, equity and inclusion (DEI) climates. The objective of this formative evaluation was to assess Mayo Clinic Department of Health Sciences Research (HSR) faculty and staff perceptions toward a proposed departmental DEI plan and to explore findings by diversity and professional subgroups. Materials and methods: Key plan components include recruitment and support for diverse individuals; training for all HSR employees and leaders; and a review system to capture diversity and inclusion feedback for leaders. Additional activities include building inclusion “nudges” into existing performance reviews. To assess pre-implementation beliefs about specific plan components, we polled attendees at a departmental staff meeting in July 2020. Results: Overall, respondents (n = 162) commonly endorsed a blinded promotion review process and DEI training for all staff and leaders as most important. In contrast, respondents expressed less support for plan activities related to “nudges.” However, attitudes among certain diversity or professional groups toward specific plan activities diverged from their non-diversity group counterparts. Qualitative feedback indicated awareness of the need to address DEI issues. Discussion: Overall, HSR faculty and staff respondents conveyed support for the plan. However, some specific plan activities were perceived differently by members of certain diversity or professional subgroups. Conclusion: These findings present a DEI framework on which other institutions can build and point to future directions for how DEI activities may be differentially perceived by impacted faculty and staff.

The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.

Abstract Introduction: Research career development awards (CDAs) facilitate development of clinician-scientists. This study compared the academic achievements of individuals in a structured institutional “pre-K” CDA program, the Mayo Clinic Kern Scholars program, with individuals who applied for but were not admitted to the Kern program (“Kern applicants”), and awardees of other unstructured internal CDAs. Methods: This was a longitudinal cohort study of clinicians engaged in research at Mayo Clinic between 2010 and 2019. The primary outcome was time to the 15th new peer-reviewed publication after the program start, adjusted for baseline number of publications. Secondarily, we described successful awarding of federal funding by the NIH or VA. Results: The median (IQR) number of baseline publications was highest among Kern Scholars compared to Kern Applicants or other CDA awardees [16 (12, 29) vs 5 (1, 11) and 8 (5, 16); P < 0.001]. After adjustment for baseline publications, the time to 15th new publication was significantly shorter for Kern Scholars than for the two comparator groups (P

Abstract Introduction: The hidden curriculum encompasses the norms, values, and behaviors within a learning environment. Navigating the hidden curricula of academia is crucial for doctoral trainees, particularly those from underrepresented backgrounds. Faculty mentors have an important role in helping trainees uncover and cope with the hidden curriculum. The purpose of this paper is to explore perceptions of the hidden curriculum among diverse doctoral trainees and mentors. Methods: Following a presentation on the hidden curriculum at the Association for Clinical and Translational Science annual meeting in March 2021, attendees were asked to brainstorm ideas for diverse trainees and their mentors. Breakout room discussions were held for specific hidden curriculum topics; participants voted on which topics to discuss from a list of topics defined during the presentation. Ideas from these discussions were presented to the larger group to upvote. Results: Participants (n = 116) voted to discuss the following hidden curriculum topics: “coping with bias,” “assertive communication,” “knowing how things work,” and “developing a career.” Many suggestions emphasized the role of institutions in empowering mentors to help diverse trainees and, more generally, to meaningfully support policies and programs that facilitate the career success of trainees and faculty from underrepresented backgrounds. Conclusions: This work generated a list of suggested action items for trainees, mentors, and institutions to ameliorate the hidden curricula of academia, especially for diverse trainees. However, institutions need to support changes that will facilitate these discussions as well as more broadly enable the success of faculty and students from diverse backgrounds.

It is very important for medical professionals and medical researchers to be literate in statistics. However, we have found that the degree of literacy that is required should not be identical for every statistical competency or even for every learner. We first begin by describing why the development, teaching, and assessment of statistical competencies for medical professionals and medical researchers are critical tasks. We next review our three substantial efforts at developing a comprehensive list of statistical competencies that can be used as a guide for what medical research learners should know about statistics, for curricular development, and for assessment of statistical education. We then summarize the origin and the inclusion of the statistical competency items. We follow this with a description of potential uses and applications of the statistical competencies to improve targeted learning for medical research learners. Finally, we discuss implications of the statistical competencies for undergraduate statistics education.

Introduction It is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from ‘fundamental’ (necessary for all) to ‘specialized’ (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized. Methods We surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by ‘fundamental’ and ‘specialized.’ Results There were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one’s own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%). Conclusion We have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.

This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8–115), 3a (HR 13.7, 95% CI 3.0–62), and 3b stages (HR 5.2, 95% CI 1.1–25), p < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1–Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.

Influenza is a global problem infecting 5-10% of adults and 20-30% of children annually. Non-pharmaceutical interventions (NPIs) are attractive approaches to complement vaccination in the prevention and reduction of influenza. Strong cyclical reduction of absolute humidity has been associated with influenza outbreaks in temperate climates. This study tested the hypothesis that raising absolute humidity above seasonal lows would impact influenza virus survival and transmission in a key source of influenza virus distribution, a community school. Air samples and objects handled by students (e.g. blocks and markers) were collected from preschool classrooms. All samples were processed and PCR used to determine the presence of influenza virus and its amount. Additionally samples were tested for their ability to infect cells in cultures. We observed a significant reduction (p < 0.05) in the total number of influenza A virus positive samples (air and fomite) and viral genome copies upon humidification as compared to control rooms. This suggests the future potential of artificial humidification as a possible strategy to control influenza outbreaks in temperate climates. There were 2.3 times as many ILI cases in the control rooms compared to the humidified rooms, and whether there is a causal relationship, and its direction between the number of cases and levels of influenza virus in the rooms is not known. Additional research is required, but this is the first prospective study suggesting that exogenous humidification could serve as a scalable NPI for influenza or other viral outbreaks.