Faculty Bibliography

OBJECTIVE:We assess diabetes risk in adulthood among adolescents with isolated glucosuria. RESEARCH DESIGN AND METHODS/METHODS:Included were adolescents (16-19 years) examined before military service between 1993 and 2015. Data were linked with the Israeli National Diabetes Registry. Glucosuria was confirmed following normal renal function and glucose tolerance tests. Cox models were applied. RESULTS:The study included 1,611,467 adolescents, of whom 755 (0.05%) had glucosuria. The latter group had a higher proportion of males (75% vs. 57%) and a lower proportion of BMI ≥ 85th percentile (10.4% vs. 16.3%) compared with nonglucosuric (all P < 0.001). During follow-up, 10,328 diabetes cases were recorded with an incidence rate of 87.5 and 43.3 per 100,000 person-years for those with versus without glucosuria, respectively. Individuals with glucosuria had an adjusted hazard ratio of 2.17 (95% CI, 1.17-4.04) for diabetes. CONCLUSIONS:Glucosuria in adolescents is associated with an increased risk of early-onset diabetes.

Obstructive sleep apnea (OSA) exerts pathogenic effects through a combination of sleep fragmentation (SF) and intermittent hypoxia (IH). The mechanisms through which sleep disruption impacts memory might arise by investigating disruption of specific sleep stages and, when such disruption occurs through OSA, by evaluating the individual contributions of SF and IH. Given region-specific EEG slow activity during non-REM sleep has been associated with overnight declarative, motor and spatial memory formation, we investigated the effects of disrupting slow wave sleep (SWS) on a virtual maze navigation task. Thirty three participants (24 male, 56 years old [range 28-68 years] with OSA (baseline AHI4%>20/hour) who were habitually well-treated and adherent to CPAP completed 3 timed trials on a 3D spatial maze before and after polysomnographically (PSG) recorded sleep. We restricted CPAP withdrawal to SWS through real-time monitoring of the PSG under three conditions: 1) stable-SWS on therapeutic CPAP, 2) SWS-CPAP withdrawal containing SF and IH, and 3) SWS-CPAP withdrawal with supplemental oxygen containing SF with reduced IH. SWS-specific CPAP withdrawal (with or without supplemental oxygen) did not significantly impact EEG slow oscillation or spatial navigational memory, despite effectively reducing %SWS and SWS bout length. Greater regional EEG slow oscillation (0.6-1Hz), but not delta (1-4Hz) activity, was associated with improvements in overnight memory during stable SWS in the CPAP condition. These observations suggest that slow oscillations may be important for overnight memory processing, and sleep disruptions of sufficient magnitude to reduce slow oscillations may be required to capture demonstrable change in spatial navigation performance.

Characterizing the chemical composition of semen can provide valuable insights into the exposome and environmental factors that directly affect seminal and overall health. In this study, we compared molecular profiles of 45 donated semen samples from general population New York City participants and examined the correlation between the chemical profiles in semen and fertility parameters, i.e., sperm concentration, sperm motility, sperm morphology, and semen volume. Samples were prepared using a protein precipitation procedure and analyzed using liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS). Non-targeted analysis (NTA) revealed 18 chemicals not previously reported in human exposome studies, with 3-hydroxyoctanedioic acid, a cosmetic additive, emerging as a plausible candidate found to be at higher levels in cases vs controls (p < 0.01) and associated with adverse sperm motility and morphology. Four level 1 identified compounds were found to have associations with semen health parameters; dibutyl phthalate and 2-aminophenol negatively impacted motility, 4-nitrophenol was associated with low morphology, while palmitic acid was found to be associated with both low morphology and low volume. This study aims to utilize NTA to understand the association of contaminants of emerging concern (CECs) along with a full chemical profile to find trends separating poor and normal semen health parameters from each other chemically. Our results suggest that the collective effects of many CECs could adversely affect semen quality.

IMPORTANCE/UNASSIGNED:The emergency department (ED) offers an opportunity to initiate palliative care for older adults with serious, life-limiting illness. OBJECTIVE/UNASSIGNED:To assess the effect of a multicomponent intervention to initiate palliative care in the ED on hospital admission, subsequent health care use, and survival in older adults with serious, life-limiting illness. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Cluster randomized, stepped-wedge, clinical trial including patients aged 66 years or older who visited 1 of 29 EDs across the US between May 1, 2018, and December 31, 2022, had 12 months of prior Medicare enrollment, and a Gagne comorbidity score greater than 6, representing a risk of short-term mortality greater than 30%. Nursing home patients were excluded. INTERVENTION/UNASSIGNED:A multicomponent intervention (the Primary Palliative Care for Emergency Medicine intervention) included (1) evidence-based multidisciplinary education; (2) simulation-based workshops on serious illness communication; (3) clinical decision support; and (4) audit and feedback for ED clinical staff. MAIN OUTCOME AND MEASURES/UNASSIGNED:The primary outcome was hospital admission. The secondary outcomes included subsequent health care use and survival at 6 months. RESULTS/UNASSIGNED:There were 98 922 initial ED visits during the study period (median age, 77 years [IQR, 71-84 years]; 50% were female; 13% were Black and 78% were White; and the median Gagne comorbidity score was 8 [IQR, 7-10]). The rate of hospital admission was 64.4% during the preintervention period vs 61.3% during the postintervention period (absolute difference, -3.1% [95% CI, -3.7% to -2.5%]; adjusted odds ratio [OR], 1.03 [95% CI, 0.93 to 1.14]). There was no difference in the secondary outcomes before vs after the intervention. The rate of admission to an intensive care unit was 7.8% during the preintervention period vs 6.7% during the postintervention period (adjusted OR, 0.98 [95% CI, 0.83 to 1.15]). The rate of at least 1 revisit to the ED was 34.2% during the preintervention period vs 32.2% during the postintervention period (adjusted OR, 1.00 [95% CI, 0.91 to 1.09]). The rate of hospice use was 17.7% during the preintervention period vs 17.2% during the postintervention period (adjusted OR, 1.04 [95% CI, 0.93 to 1.16]). The rate of home health use was 42.0% during the preintervention period vs 38.1% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of at least 1 hospital readmission was 41.0% during the preintervention period vs 36.6% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of death was 28.1% during the preintervention period vs 28.7% during the postintervention period (adjusted OR, 1.07 [95% CI, 0.98 to 1.18]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This multicomponent intervention to initiate palliative care in the ED did not have an effect on hospital admission, subsequent health care use, or short-term mortality in older adults with serious, life-limiting illness. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03424109.

BACKGROUND:Age-related hearing loss is common among older adults and may influence physical activity and sedentary behaviors, such as TV viewing. This study examined whether a hearing intervention could affect these behaviors over three years. METHODS:977 participants (mean age of 76.8, 53.5% female, 11.5% Black), recruited from the ARIC study (n=238) and de novo (n=739) with hearing loss (pure-tone average=39.4 dB), were randomized to a hearing intervention or a health education control group. Physical activity, leisurely walking, and TV viewing were interrogated at baseline and three-year follow-up. We used regression models adjusted for demographic and hearing loss severity to examine the impact of the intervention on the change in the frequency of engaging in these activities. RESULTS:At baseline, 57.6% of participants engaged in moderate-to-vigorous physical activity (MVPA), 29.1% in high-frequency leisurely walking, and 46.8% in high-frequency TV viewing. Over three years, MVPA decreased to 48.8%, while leisurely walking and TV viewing increased. After three years, the hearing intervention group had similar odds of engaging in MVPA (ratio of odds ratios [ROR] = 1.03, 95% confidence interval [CI]: 0.93 to 1.14), leisurely walking (ROR = 1.04, 95% CI: 0.93 to 1.17), and TV viewing (ROR = 0.95, 95% CI: 0.87 to 1.02) compared to the control group. Results were consistent across recruitment sources (ARIC and de novo). CONCLUSION/CONCLUSIONS:A hearing intervention did not significantly influence physical activity, walking, or TV viewing behaviors in older adults over three years. Additional strategies may be needed to change physical and sedentary behaviors in this population.

Many phthalates have been identified as endocrine-disrupting chemicals because they alter hormone functions throughout the lifespan. Nationally representative biomonitoring data are available from the United States, Canada, and Europe, but data elsewhere are sparse, making extrapolations of related disease and disability burdens difficult. We therefore examined trends in urinary phthalate metabolite concentrations in non-occupationally exposed populations in countries other than the United States, Canada, and Europe, where representative data are already available at the country level. We systematically reviewed studies published between 2000 and 2023 and analyzed changes in urinary phthalate metabolite concentrations across time using mixed-effects meta-regression models with and without a quadratic term for time. We controlled for region, age, and pregnancy status, and identified heterogeneity using Cochran's Q-statistic and I² index. Our final analysis consisted of 216 studies. Non-pregnant and youth populations exhibited nearly 2.0-fold or greater difference in concentration compared to pregnant and adult populations. Phthalates with significant regional differences had 10-fold higher concentrations in the Middle East and South Asia than in other regions. Our meta-regressions identified an exponential increase in DBP exposure through MnBP concentration internationally (beta: 0.65 ng/mL/year²) and in Eastern and Pacific Asia (EPA) (beta: 0.78 ng/mL/year²). Most DEHP and DnOP metabolites significantly declined internationally and in EPA, while MEP concentration declined by 10.62 ng/mL in Latin America and 8.98 ng/mL in Africa over time. Our findings fill gaps in phthalate exposure data and set the stage for further analysis of the attributable disease burden and cost at regional and international levels, especially in low- and middle-income countries.

Unauthorized immigrants and permanent residents may experience challenges in accessing kidney transplantation due to limited healthcare access, socioeconomic and cultural barriers. Understanding the United States (US) national landscape of kidney transplantation for non-citizens may inform policy changes. To evaluate this, we utilized two cohorts from the US national registry (2013-2023): 287,481 adult candidates for first transplant listing and 190,176 adult first transplant recipients. Citizenship was categorized as US citizen (reference), permanent resident, and presumed unauthorized immigrant. Negative binomial regression was used to quantify the incidence rate ratio over time by citizenship status. Cause-specific hazards models, with clustering at the state of listing/transplant, were used to calculate the adjusted hazard ratio of waitlist mortality, kidney transplant, and post-transplant outcomes (mortality/death-censored graft failure) by citizenship category. The crude proportion of presumed unauthorized immigrants listed increased over time (2013: 0.9%, 2023:1.9%). However, after accounting for case mix and waitlist size, there was no change in listing over time. Presumed unauthorized immigrants were less likely to experience waitlist mortality (adjusted Hazard Ratio 0.54, 95% Confidence Interval: 0.46-0.62), were more likely to obtain deceased donor kidney transplant (1.11: 1.05-1.18), but less likely to receive live donor (0.80: 0.71-0.90) or preemptive kidney transplant (0.52: 0.43- 0.62). When stratified by insurance status, presumed unauthorized immigrants on Medicaid were less likely to receive deceased donor kidney transplants compared to their citizen counterparts; however, presumed unauthorized immigrants with Private insurance or Medicare were more likely to receive deceased donor kidney transplants. Presumed unauthorized immigrants were less likely to experience post-transplant death (0.56: 0.43-0.69) and graft failure (0.69: 0.57-0.84). Residents had similar pre- and post-transplant outcomes. Despite the barriers to kidney transplantation faced by presumed unauthorized immigrants and residents in the US, better post-transplant outcomes for presumed unauthorized immigrants compared to citizens persisted, even after accounting for differences in patient characteristics.

PURPOSE OF REVIEW/OBJECTIVE:Artificial intelligence (AI) chatbots are increasingly used as a source of information. Our objective was to review the literature on their use for patient education in urology. RECENT FINDINGS/RESULTS:There are many published studies examining the quality of AI chatbots, most commonly ChatGPT. In many studies, responses from chatbots had acceptable accuracy but were written at a difficult reading level without specific prompts to enhance readability. A few studies have examined AI chatbots for other types of patient education, such as creating lay summaries of research publications or generating handouts. SUMMARY/CONCLUSIONS:Artificial intelligence chatbots may provide an adjunctive source of patient education in the future, particularly if prompted to provide results with better readability. In addition, they may be used to rapidly generate lay research summaries, leaflets or other patient education materials for final review by experts.

INTRODUCTION/BACKGROUND:There is an unmet need for tools to quantify dementia risk during its multi-decade preclinical/prodromal phase, given that current biomarkers predict risk over shorter follow-up periods and are specific to Alzheimer's disease. METHODS:Using high-throughput proteomic assays and machine learning techniques in the Atherosclerosis Risk in Communities study (n = 11,277), we developed the Dementia SomaSignal Test (dSST). RESULTS:In addition to outperforming existing plasma biomarkers, the dSST predicted mid-life dementia risk over a 20-year follow-up across two independent cohorts with different ethnic backgrounds (areas under the curve [AUCs]: dSST 0.68-0.70, dSST+age 0.75-0.81). In a separate cohort, the dSST was associated with longitudinal declines across multiple cognitive domains, accelerated brain atrophy, and elevated measures of neuropathology (as evidenced by positron emission tomography and plasma biomarkers). DISCUSSION/CONCLUSIONS:The dSST is a cost-effective, scalable, and minimally invasive protein-based prognostic aid that can quantify risk up to two decades before dementia onset. HIGHLIGHTS/CONCLUSIONS:The Dementia SomaSignal Test (dSST) predicts 20-year dementia risk across two independent cohorts. dSST outperforms existing plasma biomarkers in predicting multi-decade dementia risk. dSST predicts cognitive decline and accelerated brain atrophy in a third cohort. dSST is a prognostic aid that can predict dementia risk over two decades.