51886 research outputs found
Sort by
Alpha Testing of a Patient-Centered Decision Aid for Cleft Revision Procedures
No full textIntroduction
Cleft lip and palate are the most common craniofacial anomaly. Primary repair occurs in the first year of life, with elective revision procedures becoming available in later childhood and adolescence. The choice to undergo a cleft-related revision procedure is preference sensitive, meaning that more than one reasonable treatment option exists. Shared decision-making is standard of care for preference-sensitive decisions, and decision aids facilitate the shared decision-making process.
Methods
After IRB approval, surgeons, parents of children with cleft lip, and children with isolated cleft palate, none of whom were currently facing the decision to undergo a cleft-related revision procedure, were recruited for alpha testing. Think aloud interviews were conducted and their content transcribed for qualitative analysis and theme development. All participants completed a single item literacy screener, a decision aid acceptability scale, and a system usability scale.
Results
Participants reported an excellent level of usability and acceptability. Scores indicated that all participants found the decision aid useful in decision making. Most participants answered that the length and amount of information in the decision aid were appropriate. In analysis of qualitative data, three themes emerged: use affirming and neutral language, improve visual appeal and usability, and clarify realistic expectations.
Conclusions
To our knowledge this is the first decision aid to be developed and tested with the goal of helping children make informed choices about cleft-related revision surgery. Participants overwhelmingly found the tool helpful and serviceable. Participant feedback will guide revisions that ensure the final iteration meets the needs of patients and families. These results support the readiness of the decision aid for beta testing and eventual integration into clinical practice as a resource that enhances shared decision-making
Global Investigation of Clinical Implementation Strategies for DPYD Testing to Guide Fluoropyrimidine Therapy
No full textFluoropyrimidines are a vital component of chemotherapy regimens. Deleterious DPYD variants reduce activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme of fluoropyrimidine catabolism, resulting in reduced fluoropyrimidine clearance and elevated risk of life-threatening toxicities. DPYD genotype-guided fluoropyrimidine therapy can mitigate the risk of severe life-threatening toxicities, but adoption of testing globally has been limited. We developed a 91-item survey investigating global DPYD implementation strategies to gain insight into common practices and successful strategies. The survey was disseminated to Pharmacogenomics Global Research Network Implementation Working Group members consisting of 54 health care sites across 15 countries. Survey responses were received from 28 sites (52%) across 9 countries. Over 80% of sites implemented, or planned to implement, a preemptive testing strategy (i.e., before a fluoropyrimidine is administered) leveraging the electronic health record (EHR) to disseminate DPYD results to providers. All sites created infrastructure to support DPYD testing (e.g., order sets, EHR decision support), but 70% of sites indicated reliance on clinicians to remember test ordering. Only 2 sites reported high DPYD testing rates (> 75%) among patients planned to receive a fluoropyrimidine. Most sites (57%) used in-house clinical laboratories that tested for the majority of DPYD Tier 1 variants. Among sites that had implemented DPYD testing, the median turnaround time was 10 days. Few sites indicated that a high percentage (> 75%) of DPYD results were returned before fluoropyrimidine administration. Our results suggest that additional implementation strategies are needed, addressing barriers and facilitators of DPYD testing
Cross‐National Study to Operationalize Amyloid, Tau, Neurodegeneration, and Vascular Contributions to Dementia
No full textBackground:
Recent diagnosis and staging criteria have been proposed for AD based on amyloid(“A”), tau(“T”), and neurodegeneration(“N”), with consideration of comorbid vascular(“V”) pathology. However, challenges remain in their application and interpretation for research and clinical use. Additionally, current criteria have been largely informed by data derived from samples of highly educated, non‐Hispanic White cohorts in the US. We compared methods to operationalize multimodal ATNV measures across two cohorts to meaningfully inform future research and clinical practice.
Method:
Participants with amyloid PET, tau PET, and brain MRI were included from two prospective cohort studies with similar study designs: ADNI3 in the US and KBASE in Korea. ATNV measures were operationalized as continuous (A=centiloid; T=meta‐temporal ROI; N = AD signature region cortical thickness; V=white matter hyperintensity volume) and as binary (+/‐) variables by replicating approaches applied in other cohorts. Clinical diagnoses of cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia were determined by experts at multidisciplinary consensus conferences. Parallel cross‐sectional analyses were performed within each cohort. Multivariate logistic regressions with ATNV modeled as continuous or binary predictors (16 possible combinations) adjusting for age, sex, and education were performed to compare model fit and predictive power for distinguishing participants with dementia versus CU.
Result:
A total of 508 participants in ADNI (mean age=71±7, female=55%, education(yrs)=16.5±2.3) and 165 in KBASE (n = 165; age=73±8, female=64%, education(yrs)=11.0±4.6) were included (Table 1). In ADNI, the continuous ATNV and continuous ATN+binary V explained the most variance in dementia diagnosis (highest pseudo‐R2, lowest AIC/BIC; Table 2). In KBASE, models had higher overall predictive power for distinguishing dementia. The best‐performing models included continuous A and T, binary N, and continuous V, or binary A, continuous T, binary N, and continuous V (Table 3).
Conclusion:
Models including ATNV were highly predictive of dementia in both cohorts. Models with predominantly continuous variables explained more variability in dementia diagnosis, and are optimal for research use due to their simplicity. In Korea, binary N and binary A increased predictive power. Ongoing analyses will assess the relative contribution of ATNV to cognitive performance and diagnosis in each cohort to better inform appropriate research and clinical use in cross‐national cohorts
Prophylactic Muscle Flap Coverage in Frail Patients Undergoing Spinal Surgery
No full textBackground: Postoperative wound complications remain a significant challenge in complex spinal fusion, particularly in patients with multiple comorbidities. Prophylactic muscle flap coverage can reduce these complications, but the specific patient populations most likely to benefit have not been consistently defined. This study evaluated the utility of the five-item modified frailty index (mFI-5) scores in identifying high-risk patients who may benefit from prophylactic muscle flap closure.
Methods: The American College of Surgeons National Surgical Quality Improvement Program database (2005-2020) was queried for patients ≥50 years old undergoing posterior-approach spinal surgery with and without prophylactic muscle flap closure. Patients with mFI-5 scores ≥2 were included, while revision and non-spine procedures were excluded. A 4:1 propensity score match was performed, comparing nonflap to flap patients. Postoperative complications were assessed with chi-square and Fisher's exact tests, and outcomes were further analyzed using multivariate logistic regression.
Results: A total of 680 patients who underwent nonflap reconstruction were matched to 170 patients who underwent flap reconstruction. On univariate analysis, flap coverage was associated with reduced superficial surgical site infection (SSI) (0.6% vs 3.4%, p = 0.049) and increased bleeding requiring transfusion (35.3% vs 5.1%, p < 0.0001). On multivariate analysis, flap reconstruction was independently associated with a 94% reduction in odds of superficial SSI (odds ratio [OR], 0.062; 95% confidence interval [CI], 0.008-0.498; p = 0.022), while higher body mass index (kg/m2) independently predicted SSI risk (OR, 1.09 per unit; 95% CI, 1.03-1.16; p = 0.003). Bleeding requiring transfusion was no longer significant.
Conclusion: Prophylactic muscle flap coverage significantly reduces superficial infection in frail patients (mFI-5 scores ≥2) undergoing spinal surgery. This provides a standardized framework to identify high-risk patients most likely to benefit from this approach
The role of IL-10 in antiviral immune memory development
No full textViral infections induce heterogeneous memory T and B cell populations that may rapidly recall and provide protection against re-infection. The immunomodulatory cytokine interleukin-10 (IL-10) is well described for its role in restricting immunopathology during viral infection; however, less is known about its role in the development of cellular and humoral immune memory. In this review, we explore the current knowledge of the role of IL-10 in the regulation of antiviral memory T and B cell development. Furthermore, we highlight the importance of the cellular source and timing of IL-10 production in regulating this complex process
Advice From an Early-Career Digital Archivist
No full textPresentation given to the Indiana University Indianapolis Library and Information Science Digital Preservation course (LIS-S 582) in February 2026. The presentation provides advice to students pursing archives careers and learning more about digital preservation from the perspective of an early-to-mid-career digital archivist. The presentation discusses the presenter's career journey, their past positions and projects, and their current position and projects. The guest lecture was pre-recorded, and students watched it virtually
Association of Retinal Perfusion with Plasma Biomarkers of Alzheimer's Disease
No full textBackground:
The eye has been considered a ‘window to the brain’ and to several neurodegenerative brain disorders including Alzheimer's disease (AD) that display alterations in the eye, especially the retina. Plasma levels of AD biomarkers, including Aβ42/Aβ40 ratio, pTau 181, glial fibrillary acidic protein (GFAP), total Tau (tTau), and Neurofilament lightchain (NfL) are significantly altered in AD patients. We sought to evaluate the association of retinal perfusion measured using optical coherence tomography angiography (OCTA) with plasma biomarkers of AD.
Method:
Participants (31; 5 mild cognitive decline/AD, 6 subjective cognitive decline and 20 cognitively normal) underwent ophthalmological evaluation including OCTA and a blood sample. Single molecule array (Simoa) assays were used to measure plasma concentrations of Aβ42, and Aβ40, pTau181, GFAP, Ttau, and NfL. Partial Pearson correlations, covaried for age and sex, were used to compare retinal vessel and perfusion density with plasma level of the Aβ42/Aβ40 ratio, pTau181, GFAP, tTau and NfL.
Result:
Plasma Aβ42/Aβ40 showed a significant positive association with retinal vessel density (r=0.398 p = 0.036) and perfusion density (r = 0.384 p = 0.044). pTau 181 showed a significant negative association with retinal perfusion density (r=‐0.499 p = 0.041). GFAP showed a significant positive association with foveal avascular zone area in the superficial capillary plexus (r=0.554 p = 0.021).
Conclusion:
The majority of the sample was cognitively normal or mildly impaired, suggesting that retinal perfusion may be a useful tool for early diagnosis of AD‐related pathophysiology. Future longitudinal studies in larger samples and evaluating the utility of combining retinal and plasma biomarkers for predicting future progression to AD are needed
Student Journey Map
No full textThe Student Journey Map, developed by the Office of Scholar Development at Indiana University Indianapolis, assists students in developing curricular and non-curricular pathways that prepare them for applying to prestigious scholarships.Office of Undergraduate Education; Honors Colleg
Type 2 Diabetes Genetic Risk and Type 1 Diabetes Heterogeneity and Progression
No full textInsulin secretion varies widely in preclinical type 1 diabetes. To understand the pathogenesis of this metabolic heterogeneity, we asked whether genetic predisposition to type 2 diabetes, quantified by a type 2 diabetes genetic risk score (T2D-GRS), modulates β-cell function and disease progression in individuals at risk of type 1 diabetes. We analyzed 4,324 islet autoantibody–positive TrialNet Pathway to Prevention participants with genome-wide genotyping and oral glucose tolerance testing. Both T2D-GRS and the type 1 diabetes genetic risk score 2 (T1D-GRS2) differed significantly across five previously described groups defined by C-peptide area under the curve (AUC; a measure of insulin secretion). The highest C-peptide AUC group, compared with the lowest, had significantly higher T2D-GRS, lower T1D-GRS2, higher BMI z-score, greater insulin resistance, older age, and lower prevalence of male participants; multiple islet autoantibody positivity; and IA-2 or insulin autoantibody positivity. Progression to clinical (stage 3) type 1 diabetes was significantly associated with T1D-GRS2 across all groups and with T2D-GRS in all but the lowest C-peptide AUC group. In conclusion, type 2 diabetes genetic burden shapes metabolic heterogeneity and accelerates progression in preclinical type 1 diabetes. These results support the evaluation of type 2 diabetes–related mechanisms as targets to improve the prediction and prevention of type 1 diabetes.
Article highlights: Heterogeneity in β-cell function is a barrier to precision medicine in type 1 diabetes. We asked whether type 2 diabetes-associated genes influence insulin secretion and progression to clinical type 1 diabetes in autoantibody-positive individuals. A type 2 diabetes genetic risk score was associated with higher C-peptide area under the curve (AUC) and increased clinical type 1 diabetes risk in all but the lowest C-peptide AUC subgroup. Addressing type 2 diabetes mechanisms could improve type 1 diabetes prediction and prevention
410. Preliminary results of 20-valent pneumococcal conjugate vaccine (PCV20) monitoring in children through 24 months of age in the Vaccine Safety Datalink
No full textBackground:
In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) 4-dose series was licensed and approved for routine vaccination of children. In June 2023, the 20-valent pneumococcal conjugate vaccine (PCV20) 4-dose series was licensed and approved as an alternative for routine vaccination of children. Using surveillance data from the Vaccine Safety Datalink (VSD), we assessed post-licensure safety of the new PCV20 compared to a historical PCV13 control group. The VSD is a collaboration between the Centers for Disease Control and Prevention and 13 healthcare organizations that share electronic health record data and/or provide subject-matter expertise for vaccine safety surveillance and research studies.
Methods:
In February 2025, weekly sequential monitoring was initiated to estimate the rate ratio of 10 pre-specified adverse events (i.e., outcomes) following vaccination with PCV20 between June 2023-June 2025, compared to vaccination with historical PCV13 between June 2021-June 2023 in children aged 2, 4, 6, and 12-15 months of age. Analyses were conducted by PCV dose number and age group at vaccination. Within each subgroup, we used Poisson regression models with exact inference, stratified by age, sex, quarter, VSD site, and race and ethnicity.
Results:
Among 259,337 PCV20 doses and 549,321 PCV13 doses administer as of May 2025, there were no observed statistically significant signals for nine of the 10 outcomes monitored. We identified a statistically significant finding for urticaria/angioedema (ANGIO) following PCV20 dose 4 receipt (n=19,021 doses), when compared to PCV13 dose 4 receipt (n=80,960 doses) (rate ratio: 4.14; 95% CI: 1.19-16.48; p-value: 0.0251). Angioneurotic edema and vaccination-site urticaria reactions have been spontaneously reported during post approval use of PCV13 and may also be seen in post marketing experience with PCV20.
Conclusion:
During surveillance of the newly licensed PCV20 vaccine, the only statistically significant finding to date was a potential increased risk of ANGIO following PCV20 dose 4 receipt, compared to PCV13 dose 4. Medical record review to validate automated ANGIO cases is ongoing. Surveillance will conclude in November 2025, with plans for repeat analyses using chart confirmed cases