Faculty Bibliography

Former American football players are at risk for developing traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The objective of this study was to determine whether hyposmia is present in traumatic encephalopathy syndrome. The study included 119 former professional American football players, 60 former college football players, and 58 same age asymptomatic unexposed men from the DIAGNOSE CTE Research Project. All subjects included in the analysis had completed the Brief Smell Identification Test (B-SIT). Traumatic encephalopathy syndrome and the level of CTE certainty were diagnosed using the 2021 NINDS consensus diagnostic criteria. TES is categorized antemortem by provisional levels of increasing CTE certainty: Suggestive, Possible, and Probable. Former players who had traumatic encephalopathy syndrome and Probable CTE had lower B-SIT scores than those with TES and Suggestive CTE. Hyposmia was more likely in the former players with TES who were either CTE Possible or Probable than in those who did not have TES or had TES but were less likely to have CTE, CTE Suggestive. There was no difference in B-SIT scores between all former players versus unexposed men nor overall between the football players with and without TES. We conclude that lower B-SIT scores may be a clinical biomarker for underlying CTE in former American football players.

Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4-6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother-child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms.

BACKGROUND/UNASSIGNED:Tissue-based gene expression (genomic) tests provide estimates of prostate cancer aggressiveness and are increasingly used for patients considering or engaged in active surveillance. However, little is known about patient experiences with genomic testing and its role in their decision-making. METHODS/UNASSIGNED:We performed a qualitative study consisting of in-depth, semi-structured interviews of patients with low- or favourable-intermediate-risk prostate cancer managed with active surveillance. We purposively sampled to include patients who received biopsy-based genomic testing as part of clinical care. The interview guide focused on experiences with genomic testing during patients' decision-making for prostate cancer management and understanding of genomic test results. We continued interviews until thematic saturation was reached, iteratively created a code key and used conventional content analysis to analyse data. RESULTS/UNASSIGNED: = 20) mean age was 68 years (range 51-79). At initial biopsy, 17 (85%) had a Gleason grade group 1, and 3 (15%) had a grade group 2 prostate cancer. The decision to undergo genomic testing was driven by both participants and physicians' recommendations; however, some participants were unaware that testing had occurred. Overall, participants understood the role of genomic testing in estimating their prostate cancer risk, and the test results increased their confidence in the decision for active surveillance. Participants had some misconceptions about the difference between tissue-based gene expression tests and germline genetic tests and commonly believed that tissue-based tests measured hereditary cancer risk. While some participants expressed satisfaction with their physicians' explanations, others felt that communication was limited and lacked sufficient detail. CONCLUSION/UNASSIGNED:Patients interact with and are influenced by the results of biopsy-based genomic testing during active surveillance for prostate cancer, despite gaps in understanding about test results. Our findings indicate areas for improvement in patient counselling in order to increase patient knowledge and comfort with genomic testing.

BACKGROUND/UNASSIGNED:Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. OBJECTIVES/UNASSIGNED:We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

PURPOSE/OBJECTIVE:Cancer deaths in low- and middle-income countries (LMICs) will nearly double by 2040. Available evidence-based interventions (EBIs) for cancer prevention and early detection can reduce cancer-related mortality, yet there is a lack of evidence on effectively scaling these EBIs in LMIC settings. METHODS:We conducted a scoping review to identify published literature from six databases between 2012 and 2022 that described efforts for scaling cancer prevention and early detection EBIs in LMICs. Included studies met one of two definitions of scale-up: (1) deliberate efforts to increase the impact of effective intervention to benefit more people or (2) an intervention shown to be efficacious on a small scale expanded under real-world conditions to reach a greater proportion of eligible population. Study characteristics, including EBIs, implementation strategies, and outcomes used, were summarized using frameworks from the field of implementation science. RESULTS:This search yielded 3,076 abstracts, with 24 studies eligible for inclusion. Included studies focused on a number of cancer sites including cervical (67%), breast (13%), breast and cervical (13%), liver (4%), and colon (4%). Commonly reported scale-up strategies included developing stakeholder inter-relationships, training and education, and changing infrastructure. Barriers to scale-up were reported at individual, health facility, and community levels. Few studies reported applying conceptual frameworks to guide strategy selection and evaluation. CONCLUSION/CONCLUSIONS:Although there were relatively few published reports, this scoping review offers insight into the approaches used by LMICs to scale up cancer EBIs, including common strategies and barriers. More importantly, it illustrates the urgent need to fill gaps in research to guide best practices for bringing the implementation of cancer EBIs to scale in LMICs.

Artificial intelligence (AI) chatbots are becoming a popular source of information but there are limited data on the quality of information on urological malignancies that they provide. Our objective was to characterize the quality of information and detect misinformation about prostate, bladder, kidney, and testicular cancers from four AI chatbots: ChatGPT, Perplexity, Chat Sonic, and Microsoft Bing AI. We used the top five search queries related to prostate, bladder, kidney, and testicular cancers according to Google Trends from January 2021 to January 2023 and input them into the AI chatbots. Responses were evaluated for quality, understandability, actionability, misinformation, and readability using published instruments. AI chatbot responses had moderate to high information quality (median DISCERN score 4 out of 5, range 2-5) and lacked misinformation. Understandability was moderate (median Patient Education Material Assessment Tool for Printable Materials [PEMAT-P] understandability 66.7%, range 44.4-90.9%) and actionability was moderate to poor (median PEMAT-P actionability 40%, range 0-40%The responses were written at a fairly difficult reading level. AI chatbots produce information that is generally accurate and of moderate to high quality in response to the top urological malignancy-related search queries, but the responses lack clear, actionable instructions and exceed the reading level recommended for consumer health information. PATIENT SUMMARY: Artificial intelligence chatbots produce information that is generally accurate and of moderately high quality in response to popular Google searches about urological cancers. However, their responses are fairly difficult to read, are moderately hard to understand, and lack clear instructions for users to act on.

BACKGROUND:Abnormal orthostatic blood pressure (BP) regulation may result in cerebral hypoperfusion and brain ischemia and contribute to dementia. It may also manifest as early symptoms of the neurodegenerative process associated with dementia. The relationship between the magnitude and timing of orthostatic BP responses and dementia risk is not fully understood. METHODS:We conducted a prospective cohort analysis of the associations of orthostatic BP changes and self-reported orthostatic dizziness with the risk of dementia in the Atherosclerosis Risk in Communities study (ARIC). We calculated changes in BP from the supine to the standing position at 5 measurements taken within 2 minutes after standing during the baseline visit (1987-1989). The primary outcome was adjudicated dementia ascertained through 2019. RESULTS:Among 11 644 participants (mean [SD] age, 54.5 [5.7] years; 54.1% women; 25.9% Black), 2303 dementia cases were identified during a median follow-up of 25.9 years. Large decreases in systolic BP from the supine to standing position measured at the first 2 measurements ≈30 and 50 seconds after standing, but not afterward, were associated with orthostatic dizziness and a higher risk of dementia. Comparing a decrease in systolic BP of ≤-20 or >-20 to -10 mm Hg to stable systolic BP (>-10 to 10 mm Hg) at the first measurement, the adjusted hazard ratios were 1.22 (95% CI, 1.01-1.47) and 1.10 (95% CI, 0.97-1.25), respectively. CONCLUSIONS:Abnormal orthostatic BP regulation, especially abrupt drops in BP within the first minute, might be early risk markers for the development of dementia. Transient early orthostatic hypotension warrants more attention in clinical settings.

Anecdotal evidence of superior efficacy and lack of extrapyramidal symptoms in treating schizophrenia made clozapine a promising therapy in the United States during the early 1970s. In 1975, however, numerous fatal cases of clozapine-related agranulocytosis in Finland nearly ended the drug's development. Convinced of the significant benefits to patients, some clinicians in the United States advocated having clozapine available on a case-by-case humanitarian basis, which eventually helped resurrect the drug for Food and Drug Administration approval in 1989. This article builds on previous literature by utilizing oral histories from clinicians, researchers, and a patient's family member to understand how clozapine was saved. Exploring these stakeholders' perspectives has value to modern clinicians, who underprescribe the drug despite demonstrable benefits for treatment-resistant schizophrenia and suicide prevention.