Faculty Bibliography

AIMS/OBJECTIVE:Early identification of individuals at risk for type 2 diabetes (T2D) is essential for prevention. We evaluated a novel model-derived disposition index without insulin (mDI-woI), which requires only glucose values from a three time-point oral glucose tolerance test (OGTT: 0, 60, 120 min). METHODS:) followed biennially for up to 14 years with repeated OGTTs, we compared baseline mDI-woI with current diabetes biomarkers and the oral disposition index (oDI) using AUC-ROC analyses. RESULTS:mDI-woI and mean OGTT glucose (mean G) showed the strongest prediction for incident T2D (AUC = 0.79 each), outperforming fasting plasma glucose (0.67), 1 h-PG (0.77), 2 h-PG (0.72), HbA1c (0.71), and oDI (0.68; all P < 0.001). In individuals who progressed to T2D, baseline mDI-woI, mean G, and 1-PG exceeded their thresholds while fasting and 2 h glucose were still below prediabetes cutoffs, indicating earlier risk detection. Moreover, the novel marker mDI-woI is the earliest one, 4 years earlier than mean G and 4.5 years earlier than 1 h-PG, the next two earliest. CONCLUSIONS:Using only three glucose measurements without measuring insulin, mDI-woI provides a simple, sensitive, and clinically practical early marker that outperforms current diabetes criteria for predicting T2D progression, with strong potential for large-scale studies.

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.

We characterize within-city life expectancy gaps and their correlation with social and environmental characteristics in 948 US cities. Life expectancy estimates were drawn from the US Life Expectancy Estimation Program. City life expectancy gaps were calculated by subtracting the lowest tract-level life expectancy estimate from the highest for each city. Correlations were established using Spearman's correlation coefficient. The average city-level life expectancy gap in our sample was 11.8 years. Life expectancy gaps were larger in cities with lower average life expectancy and were evident across the USA. Life expectancy gaps of a decade were seen even in smaller cities and in high life expectancy cities. Life expectancy gaps were most strongly correlated with racialized residential segregation, children in poverty, and household income. Significant between-neighborhood gaps in life expectancy exist across US cities. Life expectancy gaps present a compelling target for establishing robust health equity goals.

OBJECTIVES/OBJECTIVE:To examine how media, geography, race, and social factors shaped patient experiences to inform strategies for improving trust and care. DESIGN/METHODS:We conducted a cross-sectional online survey of experiences and perceptions of OB/GYN care and medical mistrust using a stratified, randomised sampling approach. SETTING/METHODS:The survey was distributed through Prolific. POPULATION/METHODS:Inclusion criteria included assigned female at birth, age between 18 and 40 years, and residing in the United States. MAIN OUTCOME MEASURES/METHODS:Gender preference of OB/GYN clinician, demographic association with negative OB/GYN experiences, and degree of medical mistrust. RESULTS:Of 579 respondents, 93% identified as women, 33.9% as LGBTQIA+, and 45.2% had a history of pregnancy. Anxiety was the most common (46.4%) emotion experienced when receiving OB/GYN care, and 25.8% reported negative experiences, primarily from minimization of concerns (68.5%). A majority (65.3%) preferred receiving care from a female OB/GYN. Identifying as Republican was associated with higher odds of having had a negative experience with an OB/GYN, whereas Asian race and lower education were linked to lower odds. Black, Asian, and multiracial participants were more likely to have a racial preference for clinicians. Medical mistrust was higher among Black respondents and those with lower education. Feeling heard by a clinician was the strongest predictor of care satisfaction. CONCLUSION/CONCLUSIONS:Anxiety and negative experiences were prevalent among participants. Feeling heard was the strongest predictor of patient satisfaction, highlighting the importance of patient-centred OB/GYN care to reduce mistrust and improve patient experiences, particularly for marginalised groups.

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.

ObjectiveWe designed a survey to determine the prevalence of sexual dysfunction among cancer patients and to understand the gaps in provider-patient communication.MethodsAn IRB-approved 36-item survey was distributed through the Jefferson Recruitment Enhancement Service team and social media. Questions assessed the impact of cancer treatment on sexual health, provider communication, how sexual health was assessed, and possible interventions. Chi-square test or Fisher's exact test were used to compare the group differences with a P-value threshold (α) of 0.05 for statistical significance.Results916 patients responded to the survey, with most being diagnosed with breast (n = 271, 29.6%) and prostate cancer (n = 358, 39.1%). 71.8% of patients experienced an impact on sexual function by cancer treatment. Most experienced issues with their sexual desire, body image, arousal, comfort during intercourse, and ability to achieve orgasm (α < 0.001). Only 35.5% reported being asked about their sexual health by an oncologist and only 22.2% were given a questionnaire to assess their sexual health (α < 0.001). 49.8% of breast patients and 15.4% of prostate patients were never told their sexual health could be affected by their cancer treatment (α < 0.001). 60.3% of prostate patients were formally asked about their sexual health by an oncologist compared to 21.4% of breast patients (α < 0.001). 74% of respondents stated it is essential for oncologists to speak to patients about sexual health.ConclusionCancer survivors believe it is important for providers to discuss sexual health. However, providers are more inclined to address sexual health concerns with male patients than with female counterparts.

PURPOSE/OBJECTIVE:To evaluate the association between socioeconomic status (SES; represented by a patient's neighborhood area deprivation index) and structural and functional measurements of the eye at initial presentation for those who eventually underwent trabeculectomy. DESIGN/METHODS:A retrospective cohort study. PARTICIPANTS/METHODS:We identify patients who underwent a trabeculectomy and had at least 1 OCT scan and 1 visual field (VF) test before undergoing surgery. Patients of any age with either progressing glaucoma or uncontrolled intraocular pressure, or both, who underwent a trabeculectomy and were a part of the DOMAIN cohort study were included. METHODS:We use a subject's first recorded OCT scan and VF test to obtain baseline structural and functional measurements. We next use patient addresses to determine their census block, which is then matched to the corresponding proxy for SES. Univariate and multivariate regressions controlling for race, age, and gender were used to analyze the associations between SES and structural and functional measurements at baseline. MAIN OUTCOME MEASURE/METHODS:The association between SES and structural and functional measures at baseline. RESULTS:Among the 154 eyes in the study, we find that living in an area with greater deprivation is associated with worse structural (larger cup volumes [CVs], thinner retinal nerve fiber layer, and ganglion cell-inner plexiform layer) and functional (lower visual field index [VFI] and mean deviation [MD]) measures at baseline. However, these associations only remained statistically significant in the multivariate analysis for CV, VFI, and MD after controlling for a patient's race, gender, and age. In addition, when comparing those living in the best and worst neighborhoods, we find that living in the area with the highest decile level of deprivation is associated with a 6.63 dB lower MD at presentation compared to those living in areas with the least deprivation. CONCLUSIONS:Lower SES is associated with worse optic nerve damage and VF performance at presentation for eyes that eventually undergo trabeculectomy surgery. FINANCIAL DISCLOSURE(S)/BACKGROUND:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.