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Indiana Dental Workforce in Context
No full textThis Bowen Policy Snapshot explores the dental workforce in Indiana, compared to contiguous states. It also looks into the Dentist and Dental Hygienist Compact across the country
Enrichment of G‐to‐U Substitution in SARS‐CoV‐2 Functional Regions and Its Compensation via Concurrent Mutations
No full textWe surveyed single nucleotide variant (SNV) patterns from 5 903 647 complete SARS-CoV-2 genomes. Among 10 012 SNVs, APOBEC-mediated C-to-U (C > U) deamination was the most prevalent, followed by G > U and other RNA editing-related substitutions including (A > G, U > C, G > A). However, C > U mutations were less frequent in functional regions, for example, S protein, intrinsic disordered regions, and nonsynonymous mutations, where G > U were over-represented. Notably, G-loss substitutions rarely appeared together. Instead, G-gain mutations tended to more frequently co-occur with others, with a marked preference in the S protein, suggesting a compensatory mechanism for G loss in G > U mutations. The temporal patterns revealed C > U frequency declined until late 2021 then resurged in early 2022. Conversely, G > U steadily decreased, with a pronounced drop in January 2022, coinciding with reduced COVID-19 severity. Vaccinated individuals exhibited a slightly but significantly higher C > U frequency and a notably lower G > U frequency compared to the unvaccinated group. Additionally, cancer patients had higher G > U frequency than general patients during the same period. Interestingly, none of the C > U SNVs were uniquely identified in 2724 environmental samples. These findings suggest novel functional roles of G > U in COVID-19 symptoms, potentially linked to oxidative stress and reactive oxygen species, while C > U remains the dominant substitution, likely driven by host immune-mediated RNA editing
Prophylactic Enoxaparin Dosing and Anti-Xa Levels in Medicine Patients With Obesity
No full textIntroduction: Previous studies have shown that the manufacturer's standard fixed dosing of enoxaparin for venous thromboembolism (VTE) prophylaxis leads to sub-prophylactic anti-Xa levels in medicine patients with obesity. Yet, there is limited literature describing higher dosing strategies in this patient population, and an optimal dosing regimen has not been well-established. Objective: The primary objective was to evaluate mean doses (mg/kg/d) of prophylactic enoxaparin that are associated with goal anti-Xa levels in medicine patients with obesity across 3 body mass index (BMI) groups (40-49 kg/m2, 50-59 kg/m2, ≥60 kg/m2). Methods: This is a single-center, retrospective cohort study of adult patients (age ≥18 years) with BMI ≥40 kg/m2 admitted to a medicine team with at least 1 appropriately drawn anti-Xa level between January 2018 and July 2023. The institution's goal anti-Xa level for VTE prophylaxis was 0.2 to 0.4 units/mL. The primary outcome was the comparison of mean dose between those within anti-Xa at goal and not at goal. Secondary outcomes included the percentages of initial anti-Xa levels below, within, or above goal range and the incidence of new VTE and major bleeding events during hospitalization while on enoxaparin. All outcomes were stratified into 3 BMI groups: 40-49 kg/m2, 50-59 kg/m2, and ≥60 kg/m2. Results: Median dose of those with final anti-Xa level at goal was significantly higher than that of those not in goal anti-Xa range across all 3 BMI groups (0.57 vs 0.50 mg/kg/d; P < 0.05). The majority of the initial anti-Xa levels were subprophylactic, with only 35.7% of patients (or 75 of 210 patients) had initial anti-Xa within the goal range. There were no statistically significant differences in the number of blood transfusions or VTE events between the groups. Conclusion: Findings suggest that medicine patients with BMI ≥40 kg/m2 may require enoxaparin doses higher than 0.5 mg/kg/d to reach goal prophylactic anti-Xa level. However, more robust data are necessary to further validate these results and the clinical implications
Association of Hepatorenal Syndrome-Acute Kidney Injury with Mortality in Patients with Cirrhosis Requiring Renal Replacement Therapy: Results from the HRS-HARMONY Consortium
No full textKey Points:
In patients with cirrhosis and AKI requiring renal replacement therapy (RRT), hepatorenal syndrome-AKI was not associated with an increased 90-day mortality when compared with other AKI etiologies.
Etiology of AKI may not be a critical factor regarding decisions to trial RRT in acutely ill patients with cirrhosis and AKI.
Although elevated, mortality rates in this study are comparable with those reported in general hospitalized patients with AKI requiring RRT.
Background: While AKI requiring renal replacement therapy (AKI-RRT) is associated with increased mortality in heterogeneous inpatient populations, the epidemiology of AKI-RRT in hospitalized patients with cirrhosis is not fully known. Herein, we evaluated the association of etiology of AKI with mortality in hospitalized patients with cirrhosis and AKI-RRT in a multicentric contemporary cohort.
Methods: This is a multicenter retrospective cohort study using data from the HRS-HARMONY consortium, which included 11 US hospital network systems. Consecutive adult patients admitted in 2019 with cirrhosis and AKI-RRT were included. The primary outcome was 90-day mortality, and the main independent variable was AKI etiology, classified as hepatorenal syndrome (HRS-AKI) versus other (non–HRS-AKI). AKI etiology was determined by at least two independent adjudicators. We performed Fine and Gray subdistribution hazard analyses adjusting for relevant clinical variables.
Results: Of 2063 hospitalized patients with cirrhosis and AKI, 374 (18.1%) had AKI-RRT. Among them, 65 (17.4%) had HRS-AKI and 309 (82.6%) had non–HRS-AKI, which included acute tubular necrosis in most cases (62.6%). Continuous renal replacement therapy was used as the initial modality in 264 (71%) of patients, while intermittent hemodialysis was used in 108 (29%). The HRS-AKI (versus non–HRS-AKI) group received more vasoconstrictors for HRS management (81.5% versus 67.9%), whereas the non–HRS-AKI group received more mechanical ventilation (64.3% versus 50.8%) and more continuous renal replacement therapy (versus intermittent hemodialysis) as the initial RRT modality (73.9% versus 56.9%). In the adjusted model, HRS-AKI (versus non–HRS-AKI) was not independently associated with increased 90-day mortality (subdistribution hazard ratio, 1.36; 95% confidence interval, 0.95 to 1.94).
Conclusions: In this multicenter contemporary cohort of hospitalized adult patients with cirrhosis and AKI-RRT, HRS-AKI was not independently associated with an increased risk of 90-day mortality when compared with other AKI etiologies. The etiology of AKI appears less relevant than previously considered when evaluating the prognosis of hospitalized adult patients with cirrhosis and AKI requiring RRT
Social Determinants of Health and Their Effects on Readmission and 30-Day Readmission in Patients with a History of Cardiovascular Interventions
No full textSocial Determinants of Health and Their Effects on Readmission and 30-Day Readmission in Patients with a History of Cardiovascular Interventions
Mark Delos Reyes, Baraka Muvuka, Jonathan Guerrero
Indiana University School of Medicine- Northwest (IUSM-NW)
Background: 30-day readmission is a quality indicator impacting patients and healthcare systems. Medicare patients accounted for 2.3 million 30-day readmissions, costing $35.7 billion 4 years following the 2012 Hospital Readmission Reduction Program (HRRP) launch . Three of six HRRP measures are cardiovascular: myocardial infarction, Heart Failure, and Coronary Artery Bypass Graft Surgery. This study examined relationships between social determinants of health (SDOH), demographics, and behavioral factors on readmission and 30-day readmission among patients with a cardiovascular intervention history in partnership with an urban Northwest Indiana (NWI)-based health system.
Methods: This retrospective study analyzed de-identified data from inpatient SDOH screenings in Epic using the Protocol for Responding to and Assessing Patients Assets, Risks and Experiences (PRAPARE) at 3 urban hospitals between January 2021 and April 2024. Data analysis included descriptive, bivariate (Chi-Square, Mann-Whitney U, Kruskal Wallis; p<0.05), and multivariate (binary logistic regression; p<0.05) analyses in SPSS 29.0. This study was exempted by the Indiana University Human Research Protection Program (IRB #14040).
Results: The sample comprised 3717 patients, majority White (70.2%), publicly insured (87.4%), and older adults (73+17). Readmissions represented 43.5% of admissions, 19.8% being 30-day readmissions. Bivariate analysis revealed significant associations between readmission and age (p<0.001), ethnicity (p=0.001), race (p<0.001), sex (p<0.001), sexual orientation (p=0.007), insurance type (p<0.001), financial resource risk (<0.001), housing risk (p=0.05), smoking status (p=0.041), BMI (p<0.001), hospital (p<0.001), and comorbidities (p=0.027). Sex, insurance type, sexual orientation, BMI, and hospital were also associated with 30-day readmission. Multivariate analysis revealed significantly higher odds of readmission with prolonged hospital stay (OR=1.051; p<0.001), former smoking (OR=1.759; p=0.039), and patients at a small, lower SES-serving hospital (OR=1.473; p<0.001).
Conclusions: Social-behavioral factors were associated with readmissions and 30-day readmissions among patients with a history of cardiovascular interventions. Integrating SDOH and behavioral screenings and interventions into hospital readmission reduction initiatives could strengthen these programs.This project was funded with support from the Indiana Clinical and Translational Sciences Institute, the National
Institutes of Health (NIH), Indiana University School of Medicine – Northwest, and Health Resources and
Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS
Advancing patient evidence in XLH (APEX): rationale and design of a real-world XLH global data unification program
No full textX-linked hypophosphatemia (XLH) is a rare, genetic, progressive, lifelong disorder caused by pathogenic variants in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, resulting in excess fibroblast growth factor 23 (FGF23) and consequent renal phosphate wasting. Chronic hypophosphatemia leads to deficits of the musculoskeletal system affecting bone, muscle, joint, and dental health. XLH treatments include oral phosphate and active vitamin D-which are associated with a burdensome dosing regimen, gastrointestinal disturbances, hyperparathyroidism, and nephrocalcinosis-or burosumab, a fully human anti-FGF23 antibody. Randomized clinical trials (RCTs) demonstrated burosumab to be well tolerated and efficacious in improving serum phosphate, rickets, bone turnover, and patient-reported outcomes. However, there are limited data on the natural history of XLH or real-world comparisons of the safety, effectiveness, and long-term outcomes of XLH treatments. Advancing Patient Evidence in XLH (APEX) is a global data unification project aiming to describe the burden and lifelong progression of XLH, collect real-world data on treatment effectiveness and safety, and investigate regional differences in treatment outcomes. Participants from three observational, noninterventional, retrospective and prospective, multicenter, longitudinal (10-year) studies of patients with XLH will be included: XLH Disease Monitoring Program (NCT03651505), International XLH Registry (NCT03193476), and SUNFLOWER (NCT03745521). Data collected in the Americas, Europe, Israel, Japan, and South Korea will be processed to unify identical and similar data elements. Data unification will be an iterative process with a clinical and programming review, ensuring validity and accuracy. In this observational study, unified data involving approximately 2000 pediatric and adult participants with XLH will be analyzed to address research questions in an exploratory manner. Long-term observational studies and patient registries provide opportunities to generate real-world data and address knowledge gaps in rare diseases. APEX aims to improve clinical decision-making and practice by bridging evidence gaps that cannot be addressed by RCTs or regional registries
Building Communities of Practice among Undergraduate STEM Departments to Foster Emergent Transformation: A Report on the Impact of Multiple-year Engagement within the PULSE Midwest and Great Plains Regional Network
No full textA vibrant ecosystem of innovation hinges on undergraduate science programs that inclusively deepen conceptual understanding, develop scientific competencies, and spark wonder and appreciation for science. To create this ecosystem, we need to influence multiple components of the system, including faculty as well as culture (i.e., rules, goals, and beliefs giving rise to them). Here we describe and evaluate a multi-institution community of practice focused on transforming undergraduate biology programs' organizational practices, behaviors, and beliefs, as well as instilling a sense of agency in community participants. The approach drew on three change theories: Community of Practice, Participatory Organizational Change, and Organizational Justice. Via mixed methods, we found that participation in the community catalyzed the flow of tangible capital (knowledge resources), grew social capital (relationships and identity), and developed human capital (creative problem-solving and facilitative leadership skills; sense of agency). In participants' home departments, application of knowledge capital was associated with increased implementation of the principles of the Vision and Change report. Departmental change was enhanced when coupled with use of capitals developed through a community of practice centered on creative problem-solving, facilitative leadership, conflict resolution, and organizational justice
Delayed cerebral vasculopathy following pneumococcal meningitis: a case report
No full textAcute bacterial meningitis (ABM) remains a common disease, especially in developing countries. Although morbidity and mortality have improved with advances in medicine, significant neurologic complications of meningitis still occur. Delayed cerebral vasculopathy (DCV) is a unique complication following ABM leading to ischemic strokes and poor functional outcomes. We describe a case of a 66-year-old man with repeated acute infarcts from DCV due to ABM, notably in the absence of empiric dexamethasone treatment, which was not administered as meningitis was diagnosed post-antibiotic initiation. New areas of acute ischemia were noted on repeat imaging on days 6, 24, and 30 of admission. Vascular imaging revealed multifocal vascular stenosis, consistent with vasospasm that was successfully treated with Milrinone
A30 Through-The-Scope Clip With Anchor Prongs For Prophylactic Clip Closure After Gi Lesion Resection: A Prospective Cohort Study
No full textBackground:
Endoscopic clipping following gastrointestinal (GI) lesion resection provides prophylaxis for delayed bleeding. A rotatable, anchor-pronged through-the-scope endoscopic clip (TTSC) underwent limited prospective study since commercialization in the USA in 2022.
Aims:
We prospectively studied 30-day delayed bleeding rates after prophylactic clip closure of lesions using the new TTSC.
Methods:
We conducted a multicenter, prospective cohort study of the anchor-pronged MANTISTM clip (Boston Scientific Corporation, Marlborough, Massachusetts, USA) used for prophylactic clipping after lesion resection at 10 sites in 6 countries (ClinicalTrials.gov number, NCT05653843). Outcomes were 1) complete defect closure without delayed bleeding at the original resection site, 2) rate of delayed bleeding at the original resection site, defined as a severe bleeding event requiring hospitalization, blood transfusion (>5 units), or another invasive intervention ≤30 days after study clip placement, 3) rate of serious device or procedure-related adverse events (SAEs).
Results:
Among 191 enrolled participants, the mean age was 65.4±12.2 (range 23-89) years, and 110 (57.6%) were male. Median maximum lesion diameter was 25.0 (range 5.0-100.0) mm. Of 199 attempted clipping procedures, 190 (95.5%) defects had complete closure without delayed bleeding at the original lesion site (Table). Delayed bleeding occurred in 1 (0.5%) patient by 30 days after the index procedure. Seven (3.7%) patients had at least one SAE, including bleeding (2 patients), perforation (1), aspiration (1), nausea (1), pneumoperitoneum (1), postpolypectomy syndrome (1). No SAEs were considered device-related.
Conclusions:
A rotatable, anchor-pronged TTSC showed high rates of procedural completion and sustained lesion closure, and low rates of delayed bleeding or other SAEs by 30 days after the index procedure
Multi-modal Imaging-based Pseudotime Analysis of Alzheimer progression
No full textAlzheimer's disease (AD) is a neurodegenerative disorder that results in progressive cognitive decline but without any clinically validated cures so far. Understanding the progression of AD is critical for early detection and risk assessment for AD in aging individuals, thereby enabling initiation of timely intervention and improved chance of success in AD trials. Recent pseudotime approach turns cross-sectional data into "faux" longitudinal data to understand how a complex process evolves over time. This is critical for Alzheimer, which unfolds over the course of decades, but the collected data offers only a snapshot. In this study, we tested several state-of-the-art pseudotime approaches to model the full spectrum of AD progression. Subsequently, we evaluated and compared the pseudotime progression score derived from individual imaging modalities and multi-modalities in the ADNI cohort. Our results showed that most existing pseudotime analysis tools do not generalize well to the imaging data, with either flipped progression score or poor separation of diagnosis groups. This is likely due to the underlying assumptions that only stand for single cell data. From the only tool with promising results, it was observed that all pseudotime, derived from either single imaging modalities or multi-modalities, captures the progressiveness of diagnosis groups. Pseudotime from multi-modality, but not the single modalities, confirmed the hypothetical temporal order of imaging phenotypes. In addition, we found that multi-modal pseudotime is mostly driven by amyloid and tau imaging, suggesting their continuous changes along the full spectrum of AD progression