Faculty Bibliography

BACKGROUND:Fetal exposure to endocrine-disrupting chemicals such as phthalates and bisphenols might lead to fetal cardiovascular developmental adaptations and predispose individuals to cardiovascular disease in later life. OBJECTIVES/OBJECTIVE:We examined the associations of maternal urinary bisphenol and phthalate concentrations in pregnancy with offspring carotid intima-media thickness and distensibility at the age of 10 y. METHODS:In a population-based, prospective cohort study of 935 mother-child pairs, we measured maternal urinary phthalate and bisphenol concentrations at each trimester. Later, we measured child carotid intima-media thickness and distensibility in the children at age 10 y using ultrasound. RESULTS: DISCUSSION/CONCLUSIONS:In this large prospective cohort, higher maternal urinary bisphenols concentrations were associated with smaller childhood carotid intima-media thickness. Further studies are needed to replicate this association and to identify potential underlying mechanisms. https://doi.org/10.1289/EHP10293.

Survival modeling with time-varying coefficients has proven useful in analyzing time-to-event data with one or more distinct failure types. When studying the cause-specific etiology of breast and prostate cancers using the large-scale data from the Surveillance, Epidemiology, and End Results (SEER) Program, we encountered two major challenges that existing methods for estimating time-varying coefficients cannot tackle. First, these methods, dependent on expanding the original data in a repeated measurement format, result in formidable time and memory consumption as the sample size escalates to over one million. In this case, even a well-configured workstation cannot accommodate their implementations. Second, when the large-scale data under analysis include binary predictors with near-zero variance (e.g., only 0.6% of patients in our SEER prostate cancer data had tumors regional to the lymph nodes), existing methods suffer from numerical instability due to ill-conditioned second-order information. The estimation accuracy deteriorates further with multiple competing risks. To address these issues, we propose a proximal Newton algorithm with a shared-memory parallelization scheme and tests of significance and nonproportionality for the time-varying effects. A simulation study shows that our scalable approach reduces the time and memory costs by orders of magnitude and enjoys improved estimation accuracy compared with alternative approaches. Applications to the SEER cancer data demonstrate the real-world performance of the proximal Newton algorithm.

Introduction: Prostate cancer diagnosis and treatment have a significant impact on sexual function and quality of life. Although prostate cancer is often called a "couples disease," there is limited research on the needs of partners who are affected by the patient's sexual dysfunction.
Objective(s): The objective of our study was to compare the sexual health concerns and unmet needs of patients with prostate cancer and partners using real-world data from an online prostate cancer community.
Method(s): We performed a mixed-methods analysis of data from the Inspire UsTOO Prostate Cancer Online Support & Discussion Community. This online health community about prostate cancer has more than 30,000 members, including both patients and partners. Through a data use agreement, we obtained anonymized text from public postings to the Sexual Health & Intimacy Forum on this community. Quantitative and qualitative data were examined from a random sample of 10% of the posts by women about sexual health (n=66), and were compared to an equal number of randomly selected posts by men.
Result(s): Among 6193 posts about sexual health and intimacy in prostate cancer, 661 (11%) were by female contributors. Of posts with cancer treatment details, surgery was the most common treatment discussed followed by hormonal therapy. Erectile dysfunction was the most common sexual complaint for both men and women. Posts by women were most likely to discuss problems with communication, relationship conflict, their partner's loss of libido, and the importance of intimacy. Common themes of the posts included coping with a "new normal" in their relationship, lack of access to and expense of erectile aids, and insufficient information and support from clinicians surrounding sexual recovery. A greater proportion of female posts conveyed emotion compared to male posts. The most common positive emotions were satisfaction and hope; while the most common negative emotions were frustration and loss of familiar sexual interaction. Although many posts discussed a variety of medical and surgical therapies for sexual recovery, very few discussed counseling or other psychosocial treatments.
Conclusion(s): Patients with prostate cancer and their partners experience a wide range of sexual health issues related to prostate cancer diagnosis and treatment. Online communities are widely used to give and receive peer-to-peer advice and support during sexual recovery. These findings highlight an unmet need for more extensive education and support surrounding sexual health for couples during the prostate cancer journey. Disclosure: No
Copyright

Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants. Trans-ethnic meta-analysis was then applied to improve fine-mapping of potential causal variants. Mean estimated glomerular filtration rate was 44.4 and 41.5 mL/min/1.73m² in the White and Black participants, respectively. There were 45 significant metabolite associations at 19 loci, including novel associations at PYROXD2, PHYHD1, FADS1-3, ACOT2, MYRF, FAAH, and LIPC. The strength of associations was unchanged in models additionally adjusted for estimated glomerular filtration rate and proteinuria, consistent with a direct biochemical effect of gene products on associated metabolites. At several loci, trans-ethnic meta-analysis, which leverages differences in linkage disequilibrium across populations, reduced the number and/or genomic interval spanned by potentially causal single nucleotide polymorphisms compared to fine-mapping in the White participant cohort alone. Across all validated associations, we found strong concordance in effect sizes of the potentially causal single nucleotide polymorphisms between White and Black study participants. Thus, our study identifies novel genetic determinants of blood metabolites in chronic kidney disease, demonstrates the value of diverse cohorts to improve causal inference in metabolomics GWAS, and underscores the shared genetic basis of metabolism across race.

OBJECTIVE:To develop a screening tool to identify emergency department (ED) patients at risk of entering a homeless shelter, which could inform targeting of interventions to prevent future homelessness episodes. DATA SOURCES/METHODS:Linked data from (1) ED patient baseline questionnaires and (2) citywide administrative homeless shelter database. STUDY DESIGN/METHODS:Stakeholder-informed predictive modeling utilizing ED patient questionnaires linked with prospective shelter administrative data. The outcome was shelter entry documented in administrative data within 6 months following the baseline ED visit. Exposures were responses to questions on homelessness risk factors from baseline questionnaires. DATA COLLECTION/EXTRACTION METHODS/METHODS:Research assistants completed questionnaires with randomly sampled ED patients who were medically stable, not in police/prison custody, and spoke English or Spanish. Questionnaires were linked to administrative data using deterministic and probabilistic matching. PRINCIPAL FINDINGS/RESULTS:Of 1993 ED patients who were not homeless at baseline, 5.6% entered a shelter in the next 6 months. A screening tool consisting of two measures of past shelter use and one of past criminal justice involvement had 83.0% sensitivity and 20.4% positive predictive value for future shelter entry. CONCLUSIONS:Our study demonstrates the potential of using cross-sector data to improve hospital initiatives to address patients' social needs.

BACKGROUND:Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix - an educational and clinical/FH collection tool to facilitate GT in practice. MATERIALS AND METHODS/METHODS:A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descriptive statistics. Semi-structured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing. RESULTS:Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use. CONCLUSION/CONCLUSIONS:Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice.

To identify biomarkers of exposure present in Heated Tobacco Products (HTPs) users' urine which are associated with bladder cancer and to compare quantitative biomarker levels to those seen in combustible cigarette users. A systematic literature review was conducted in December 2020 with no date limits. Relevant studies that reported quantitative urinary biomarker of exposure in HTP users were included. Biomarkers and their parent compounds were classified by carcinogenicity according to the International Agency for Research on Cancer Monographs and were cross-referenced with the Collaborative on Health and the Environment Toxicant and Disease Database to determine associations with bladder cancer. Our literature search identified 561 articles and 30 clinical trial reports. 11 studies met inclusion criteria. These studies identified 29 biomarkers of exposure present in HTP users' urine, which reflect exposure to 21 unique parent compounds. Of these parent compounds, 14 are carcinogens and 10 have a known link to bladder cancer. HTP users' biomarkers of exposure were present at lower levels than combustible cigarette users but higher than never-smokers. Biomarkers of exposure to bladder carcinogens are present in the urine of HTP users. While levels of these biomarkers appear to be lower than combustible cigarette users, chronic urothelial exposure to bladder carcinogens is concerning and degree of bladder cancer risk remains unknown. Further long-term study is needed to elucidate the bladder cancer risk of HTP use.