Faculty Bibliography

BACKGROUND:Germline genetic variants are important for prostate cancer (PCa) management and hereditary cancer risk assessment, but testing is underused. Furthermore, patients are often unaware of the genetic connections to PCa. Social media is increasingly serving as a source of awareness for health information and a method to gather data from a large population. OBJECTIVE:There were three objectives: to (1) create and test social media messages related to PCa genetics and genetic testing, (2) determine which social media message was most engaging, and (3) assess knowledge of and attitudes toward PCa genetic testing through an online survey using the most engaging social media message. METHODS:A paid social media campaign was developed to disseminate targeted messages about PCa and genetics. We tested combinations of 8 images and 8 messages that were created or selected by the research team and reviewed by a study-specific advisory board. We targeted men and women older than 35 years living in the United States. The campaign was launched on Facebook for 6 days (June 3-8, 2023). We tracked the reach and impressions of each post. The survey, administered directly after someone viewed a post, assessed knowledge about PCa and cancer genetics as well as beliefs about cancer risk and genetic testing. Descriptive and multivariable analyses were used to analyze survey data. RESULTS:Most posts were viewed by women (13,675/16,224, 84.3% of impressions) and people over the age of 55 years (19,997/22,906, 87.3% of impressions). The 2 most engaging images were a group of men of different races and ethnicities (reach: 28,151 people; impressions: 33,727 views), followed by a Hispanic family (reach: 16,026 people; impressions: 20,113 views). The following message had the most engagement: "Breast cancer and prostate cancer may be related because they can arise from the same gene mutation in a family" (reach: 58,980 people; impressions: 74,834 views). A total of 875 people (n=796, 91% male; mean age 43.42, SD 14.1 years; n=224, 25.6% Black or African American individuals; n=255, 29.1% Hispanic individuals) completed the survey. In total, 75.2% (658/875) strongly or somewhat agreed that genetics play a role in the development of PCa, and 84% (735/875) would want to know if they had a genetic predisposition to PCa. CONCLUSIONS:It is feasible to use social media platforms to test and disseminate messages that raise awareness about PCa genetics and the connection with other cancers (eg, breast cancer), as well as to deploy surveys that reach a wide audience.

Exposure to organophosphate pesticides (OPPs) has been linked to adverse birth outcomes, including low birthweight. Maternal biomarkers are commonly used as proxies for fetal exposure, but fetal exposure also depends on placental transport mechanisms. In 240 mother-newborn pairs, we explored how genetic variation in membrane transporters influences the association between maternal OPP concentrations and birthweight. Single nucleotide polymorphisms (SNPs) in the OAT4/SLC22A11 and OATP2B1/SLCO2B1 membrane transporters modified the relationship between OPP exposure and birthweight-for-gestational age, with significant inverse associations observed only among individuals with variant transporter genotypes. In this small study, we found that transporter genotype may influence the placental disposition of environmental chemicals and perinatal susceptibility to toxicity.

We conducted an umbrella review to synthesize the evidence on the diagnostic performance of liquid biopsy tests for detection of head and neck squamous cell carcinoma (HNSCC). Systematic reviews (SRs) were searched in Medline, Embase, and Google Scholar through December 6, 2023. The Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews was used to assess methodological quality. Two independent reviewers extracted data. We examined the pooled sensitivity and specificity of biomarker classes. We also statistically pooled sensitivity and specificity of individual biomarkers for oral SCC in cases where meta-analysis was not yet published, since most HNSCC occurs in the oral cavity. Performance was also assessed by specimen type (saliva, serum, plasma, and whole blood). Thirty-one SRs met inclusion criteria and 21 included meta-analyses on transcriptomic, proteomic, genomic, or metabolomic biomarkers. Overall methodologic quality was moderate to high. Primary study overlap was ≥ 15 % in 9.3 % of SR pairwise comparisons. MicroRNA (miRNA) was the biomarker class represented in the most SRs (n = 19) and individual studies (n = 106). Among these, the highest sensitivity was 77 % (95 % CI, 68-84 %), observed in miRNA-21. Hypermethylated DNA was the biomarker class with the highest pooled sensitivity (86 %; 95 % CI, 60-96 %) and specificity (92 %; 95 % CI, 80-97 %) overall, and with superior performance when used in panels compared to individual markers. In studies focused on OSCC detection, no other biomarker class or fluid type demonstrated superior performance over others. In future clinical studies, panels including hypermethylated DNA merit more rigorous evaluation to establish high specificity in addition to sufficient sensitivity.

BACKGROUND:Glaucoma Research Foundation's third Catalyst for a Cure team (CFC3) was established in 2019 to uncover new therapies for glaucoma, a leading cause of blindness. In the 2021 meeting "Solving Neurodegeneration," (detailed in Mol Neurodegeneration 17(1), 2022) the team examined the failures of investigational monotherapies, issues with translatability, and other significant challenges faced when working with neurodegenerative disease models. They emphasized the need for novel, humanized models and proposed identifying commonalities across neurodegenerative diseases to support the creation of pan-neurodegenerative disease therapies. Since then, the fourth Catalyst for a Cure team (CFC4) was formed to explore commonalities between glaucoma and other neurodegenerative diseases. This review summarizes outcomes from the 2023 "Solving Neurodegeneration 2" meeting, a forum for CFC3 and CFC4 to share updates, problem solve, plan future research collaborations, and identify areas of unmet need or opportunity in glaucoma and the broader field of neurodegenerative disease research. MAIN BODY/METHODS:We summarize the recent progress in the field of neurodegenerative disease research and present the newest challenges and opportunities moving forward. While translatability and disease complexity continue to pose major challenges, important progress has been made in identifying neuroprotective targets and understanding neuron-glia-vascular cell interactions. New challenges involve improving our understanding of the disease microenvironment and timeline, identifying the optimal approach(es) to neuronal replacement, and finding the best drug combinations and synergies for neuroprotection. We propose solutions to common research questions, provide prescriptive recommendations for future studies, and detail methodologies, strategies, and approaches for addressing major challenges at the forefront of neurodegenerative disease research. CONCLUSIONS:This review is intended to serve as a research framework, offering recommendations and approaches to validating neuroprotective targets, investigating rare cell types, performing cell-specific functional characterizations, leveraging novel adaptations of scRNAseq, and performing single-cell sorting and sequencing across neurodegenerative diseases and disease models. We focus on modeling neurodegeneration using glaucoma and other neurodegenerative pathologies to investigate the temporal and spatial dynamics of neurodegenerative disease pathogenesis, suggesting researchers aim to identify pan-neurodegenerative drug targets and drug combinations leverageable across neurodegenerative diseases.

Genome-wide association studies have revealed that the genetic architectures of complex traits vary widely, including in terms of the numbers, effect sizes, and allele frequencies of significant hits. However, at present we lack a principled way of understanding the similarities and differences among traits. Here, we describe a probabilistic model that combines the effects of mutation, drift, and stabilizing selection at individual sites with a genome-scale model of phenotypic variation. In this model, the architecture of a trait arises from the distribution of selection coefficients of mutations and from two scaling parameters. We fit this model for 95 highly polygenic quantitative traits of different kinds from the UK Biobank. Notably, we infer that all these traits have fairly similar, though not identical, distributions of selection coefficients. This similarity suggests that differences in architectures of highly polygenic traits arise mainly from the two scaling parameters: the mutational target size and heritability per site, which vary by orders of magnitude among traits. When these two scale factors are accounted for, we find that the architectures of all 95 traits are very similar.

BACKGROUND:Fall injury is a sentinel event for mortality among older adults, and activity intensity may play a role in mitigating this outcome. This study assessed the relationship between activity intensity and all-cause mortality following fall injury among community-dwelling U.S. older adults. METHODS:For this retrospective cohort study, we pooled 12 years of data from the National Health Interview Survey and identified older adults (aged 65 years and older) who sustained fall injuries (N = 2454). The outcome variable was time to death following a fall injury. We defined activity intensity as a binary variable, none-to-low and normal-to-high, using the American Heart Association's weekly 500 Metabolic Equivalent of Task (MET) as a cutoff. We controlled for sociodemographic, healthcare access, and health characteristics; performed survey-weighted Cox proportional hazard regression analysis; and reported the adjusted mortality risks (plus 95% confidence interval (CI)). RESULTS:The survey comprised 2454 older adults with fall injuries, representing 863,845 US older adults. The population was predominantly female (68%), non-Hispanic White (85%), and divorced/separated (54%). During the follow-up period, 45% of the study population died. Approximately 81% of the study population had low activity levels. However, between 2006 and 2017, the proportion of the study population with low physical activity decreased from 90% to 67%. After adjusting for sociodemographic, healthcare access, and health characteristics, none-to-low activity intensity was associated with 50% increased mortality risk (aHR: 1.50; 95% CI: 1.20-1.87). CONCLUSIONS:Promoting higher physical activity levels may significantly reduce the all-cause mortality risk following fall injury among older adults.

Social media can benefit prostate cancer care through education and empowerment, but also have the potential for exposure to misinformation, leading to adverse health and/or economic impacts for patients and damaging the patient-physician relationship. Clinicians should promote digital health literacy and provide recommended sources of reliable online content for additional information.

BACKGROUND/UNASSIGNED:Despite their efficacy, medications for opioid use disorder (MOUD) remain underutilized in patients with infections from intravenous opioid use (I-IOU). This study evaluates the impact of an Expanded MOUD Access Initiative (EMAI) on MOUD uptake and other clinical outcomes in patients hospitalized for I-IOU at an institution without addiction medicine consultation. METHODS/UNASSIGNED:We performed a retrospective pre-post study of hospital admissions for I-IOU before (January 2019-June 2021) and after (January 2022-December 2023) EMAI introduction. Data was collected via chart review. The EMAI eliminated restrictions on methadone use and established a new order set for buprenorphine inductions. The primary outcome was MOUD receipt; secondary outcomes included patient directed discharge (PDD) and 30-day re-hospitalization. RESULTS/UNASSIGNED:There were 129 hospitalizations prior to the intervention (control) and 98 after (EMAI). MOUD receipt was significantly higher in the EMAI group (75.5% vs 31.0%; OR, 6.86 [95% CI, 3.84-12.61]). In patients not receiving MOUD prior to admission (n = 176), new inductions occurred more frequently in the EMAI group (68.0% vs 11.9%; OR, 15.76 [95% CI, 7.50-35.78]). PDD was lower in the EMAI group (23.5% vs 48.8%; OR, 0.32 [95% CI, 0.10-0.57]), as was 30-day re-hospitalization (12.2% vs 22.5%; OR, 0.48 [95% CI, 0.22-0.98]). In a multivariable logistic regression model, the EMAI was the only variable to show a statistically significant association with MOUD receipt (aOR, 6.89 [95% CI, 3.75-13.11]). CONCLUSIONS/UNASSIGNED:The EMAI was associated with increased MOUD uptake, reduced PDD, and fewer 30-day re-hospitalizations despite the lack of addiction medicine consultation.

INTRODUCTION/BACKGROUND:The United States is facing an opioid use disorder (OUD) epidemic, marked by unprecedented overdose death rates. In New York State, synthetic opioids significantly contribute to the increasing overdose deaths, disproportionately impacting Black and Latinx communities. There is an urgent need to address issues related to equitable access to and the quality of care provided by substance use disorder (SUD) treatment programs. In light of this, the Quality Measurement and Management Research Center (QM2-RC) brought together an academic-government partnership to develop a person-centered quality measurement system and to assess its impact on a statewide treatment system that serves approximately 180,000 individuals per year. METHODS AND ANALYSIS/METHODS:The QM2-RC encompasses three interconnected projects (Project 1, 2, and 3) aimed at developing a quality management strategy and evaluating its impact on system performance across New York State. This report specifically focuses on Project 3, which involves a stepped-wedge trial with 35 clinics receiving a quality management intervention that includes performance coaching. This intervention will be compared to a treatment-as-usual (TAU) condition for clinics not participating in the trial. Administrative data will be utilized to monitor outcomes over four years. The coaching intervention, guided by the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) model, emphasizes interpreting quality measures and applying insights to enhance care. Coaches will provide support on data utilization, patient-centered care, harm reduction strategies, and the use of patient monitoring tools. The trial aims to evaluate clinic staff and leadership attitudes, experiences, and behaviors through surveys, semi-structured interviews, and external facilitator notes. Primary clinic outcomes will be assessed through adverse events, decreased clinic rates of substance use related emergency department visits and hospitalizations as well as mortality among patients within the first 12 months after admission to treatment after adjusting for individual and community level characteristics. This study is being developed over a multi-year period and will be informed by a mixed-methods approach incorporating multiple data sources, qualitative interviews, patient and clinic surveys. The study is being conducted in partnership with New York State Office of Addiction Services and Supports (OASAS) and will be informed by input from patient, providers, health insurers, family members and local governing units. DISCUSSION/CONCLUSIONS:Project 3 of the QM2 study specifically targets key barriers in measuring the quality of SUD treatment, including technological limitations, unvalidated measures, workforce data literacy, and concerns about fairness in assessing clinical complexity. Through the implementation of a stepped-wedge trial involving 35 clinics, the project aims to develop new quality measures, offer performance feedback, and engage clinic leadership and staff in efforts to improve practices. The ultimate goal of Project 3 is to overcome these barriers, promote person-centered care, and improve SUD treatment practices across New York State.