Faculty Bibliography

PURPOSE/OBJECTIVE:A critical function of public health is to monitor diseases that impede quality of life and burden affected communities. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network aims to advance disease monitoring for diabetes using multi-site electronic health record (EHR) data. METHODS:This work involved validating and refining case definitions for accurate identification of type 1 and type 2 diabetes cases to estimate incidence and prevalence of diabetes in children, adolescents, and young adults through age 44 years. RESULTS:In this essay, we describe the challenges experienced by the Network and lessons learned. Challenges included accessing EHR data, harmonizing EHR data from heterogeneous health systems to a common data model, and developing methods to account for bias introduced by the non-representativeness of health care utilization data. Lessons learned included approaches for data quality assessment, bias correction, and scalability. CONCLUSIONS:As the US continues to evolve its public health data systems and its approach to chronic disease monitoring, the DiCAYA Network offers guidance on factors for success as well as pitfalls to avoid.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem, but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer's disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). CSF was collected under controlled conditions using collection, processing, and cryostorage kits provided by the DIAGNOSE CTE Research Project Biomarker Core, and concentrations of Aβ₄₀, Aβ₄₂, tTau, and pTau (pTau₁₈₁, pTau₂₁₇, pTau₂₃₁) were measured at the University of Gothenburg, Sweden, using immunoassays. Associations between CSF biomarker levels with football history, and diagnosis of traumatic encephalopathy syndrome (TES) were examined using linear regression, and corrected for age, education, APOE-ε4 allele status, race, and body mass index. Our analysis revealed that football exposure affected both CSF Aβ₄₀ (p = 0.039) and Aβ₄₂ (p = 0.038), particularly among those under 60 years of age in the PRO compared to the UE exposure group. Among former football players, estimates of RHI exposure were not generally associated with CSF Aβ, tTau, and pTau biomarker levels. CSF Aβ₄₀ (p = 0.0041) and Aβ₄₂ (p = 0.011) were lower in former football players with TES diagnosis compared to unexposed participants, although CSF Aβ, tTau, and pTau biomarker levels did not differ between former players with and without a TES diagnosis. Among former football players, reduced CSF Aβ₄₀ (p = 0.011) and Aβ₄₂ (p = 6e-04) were observed in those with cognitive impairment compared to those with neurobehavioral dysregulation. The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.

PURPOSE/OBJECTIVE:Hemorrhagic radiation cystitis (HRC), a complication of pelvic radiation therapy, results from hypoxic and ischemic injury and causes urinary symptoms like hematuria, dysuria, frequency, urgency, and retention. Hyperbaric Oxygen Therapy (HBOT), where patients breathe 100% oxygen at increased atmospheric pressure, enhances tissue oxygenation, promoting neovascularization and reducing inflammation. The optimal pressure remains unclear, though pressures above 1.41 ATA are efficacious, with higher pressures increasing side effect risks. This study compares the efficacy and side effects of 2.0 versus 2.5 ATA therapy at two sites. MATERIALS AND METHODS/METHODS:A retrospective chart review of 93 patients treated for HRC at two sites was conducted. Data on demographics, efficacy (symptom reduction), and side effects were analyzed using GraphPad Prism. Chi-squared and Mann-Whitney tests were used for statistical analysis. Mixed effects logistic regression models were used. RESULTS AND CONCLUSIONS/CONCLUSIONS:Fewer patients treated at 2.5 ATA experienced gross hematuria within 1-year post-therapy compared to those treated at 2.0 ATA (p < 0.05). However, time to hematuria recurrence showed no difference between the groups (10.2 vs. 9.6 months). No difference was observed in other urinary symptoms. Adverse events were increased at 2.5 ATA when analyzed with a mixed effects logistic regression model. Other treatment parameters, including treatment number and duration, were similar across groups. These findings suggest an association between 2.5 ATA treatment and lower rates of hematuria recurrence, but further randomized studies are necessary to determine causality. Future studies should also assess quality of life and explore variations in treatment protocol for efficacy and safety. CLINICAL TRIAL REGISTRATION/BACKGROUND:As this is a retrospective study, no clinical trial registration is necessary.

AIMS/OBJECTIVE:To describe management of life with a left ventricular assist device (LVAD) by patients and caregivers and to determine the fit of self- and family management as a guiding concept in LVAD research. METHODS AND RESULTS/RESULTS:We applied dimensional analysis techniques to this concept analysis, beginning with a literature search (2010-25) of PubMed, CINAHL, Embase, PsycINFO, and Web of Science. Two reviewers screened and analysed 28 articles capturing perspectives on daily LVAD management among patients, caregivers, and healthcare professionals. Fourteen studies were qualitative, 12 were quantitative, and 2 were mixed methods. We identified five dimensions of patient and family management of LVAD therapy: patient facilitators and barriers; caregiver facilitators and barriers; processes of self- and family management; clinician facilitators and barriers/processes; and outcomes. These dimensions align with the concept of self- and family management and with core components of the Middle Range Theory of Self- and Family Management of Chronic Illness. CONCLUSION/CONCLUSIONS:This dimensional concept analysis advances understanding of managing life with an LVAD by clarifying the collaborative roles of patients, caregivers, LVAD coordinators, and other healthcare professionals. Our analysis supports the use of self- and family management as a guiding concept and the application of the Middle Range Theory of Self- and Family Management of Chronic Illness in LVAD research. A new conceptual definition of LVAD self- and family management reflects this theoretical grounding. Our work offers direction for future research, clinical practice, and education aimed at improving outcomes for patients and caregivers managing life with an LVAD.

The prevalence and incidence of prediabetes in children and youth continue to increase in parallel with the obesity epidemic. While prediabetes is defined by elevated HbA1c and/or impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), the risk of clinical disease is a continuum. Individuals with prediabetes are at a higher risk of developing youth-onset type 2 diabetes, which is considered a more aggressive form of the disease. This condition is associated with increased cardiovascular and metabolic risks and leads to an earlier onset of complications compared to adults with type 2 diabetes. Additionally, significant damage to beta cells may occur even before dysglycemia develops. Recent data indicate that mortality rates are higher in youths with type 2 diabetes compared to those with type 1 diabetes. Childhood prediabetes and cardiovascular complications associated with it are a significant health concern. This review provides the latest insights into this complex issue. We will present an overview of pathophysiology, screening methods, and therapeutic options to prevent the progression from prediabetes to type 2 diabetes in children. In summary, it is crucial to identify prediabetes in children, as this underscores the importance of appropriate screening and timely intervention.