Implementing a Responsible Conduct of Research Curriculum for an Undergraduate Summer Clinical Research Program in Quantitative Sciences.

Objectives: Instilling the principles of ethical and responsible medical research is critical for educating the next generation of clinical researchers. We developed a responsible conduct of research (RCR) workshop and associated curriculum for undergraduate trainees in a quantitative clinical research program.

Methods: Topics in this 7-module RCR workshop are relevant to undergraduate trainees in quantitative fields, many of whom are learning about these concepts for the first time.

Multi-Cancer Early Detection Tests: State of the Art and Implications for Radiologists.

Multi-cancer early detection (MCED) tests are already being marketed as noninvasive, convenient opportunities to test for multiple cancer types with a single blood sample. The technology varies-involving detection of circulating tumor DNA, fragments of DNA, RNA, or proteins unique to each targeted cancer. The priorities and tradeoffs of reaching diagnostic resolution in the setting of possible false positives and negatives remain under active study.

Pharmacist-Led Video Consultation to Identify and Mitigate Drug Interactions Among Patients Initiating Oral Anticancer Drugs.

Purpose: The past decade has seen an increase in oral anticancer drug (OACD) approvals. Polypharmacy and drug-drug interactions (DDIs) likely contribute to OACD toxicity. We assessed a one-time pharmacist-led video consultation to identify DDIs.

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

Background: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine-induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions.

Methods: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population-level SARS-CoV-2 seroprevalence.

Trends in uterine cancer incidence in the United States: The contribution of age, period and cohort effects.

Objective: In the U.S., uterine cancer incidence is rising, with racial and ethnic minorities experiencing the largest increases.

The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

Background: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition.

Excess morbidity and mortality associated with underuse of estrogen replacement therapy in premenopausal women who undergo surgical menopause.

Background: Contrary to clinical guidelines, there has been a decrease over time in estrogen therapy use in premenopausal women undergoing bilateral oophorectomy for benign indications.

Objective: This study aimed to estimate the excess morbidity and mortality associated with current patterns of estrogen therapy use in women who undergo bilateral oophorectomy with hysterectomy for benign indications.

Study Design: We developed 2 Bayesian sampling Markov state-transition models to estimate the excess disease incidence (incidence model) and mortality (mortality model).

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

Background: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine- induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions.

Methods: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population- level SARS-CoV-2 seroprevalence.

Cost-Effectiveness of Adjuvant Olaparib for Patients With Breast Cancer and Germline BRCA1/2 Mutations.

Importance: The OlympiA trial found that 1 year of adjuvant olaparib therapy can improve distant disease-free survival and overall survival from early-stage breast cancer in patients with a germline BRCA1/2 mutation. However, olaparib, an oral poly-adenosine diphosphate ribose polymerase inhibitor, is estimated to cost approximately $14 000 per month in the US.

Objective: To estimate the incremental cost-effectiveness of adjuvant olaparib compared with no olaparib in eligible patients.

Placental cell conditioned media modifies hematopoietic stem cell transcriptome invitro.

Introduction: Hematopoietic stem cells are cells that differentiate into blood cell types. Although the placenta secretes hormones, proteins and other factors important for maternal/fetal health, cross-talk between placental and hematopoietic stem cells is poorly understood. Moreover, toxicant impacts on placental-hematopoietic stem cell communication is understudied.

Association Between Copayment Assistance, Insurance Type, Prior Authorization, and Time to Receipt of Oral Anticancer Drugs.

Purpose: Oral anticancer drugs (OACDs) have become increasingly prevalent over the past decade. OACD prescriptions require coordination between payers and providers, which can delay drug receipt. We examined the association between insurance type, pursuit of copayment assistance, pursuit of prior authorization (PA), and time to receipt (TTR) for new OACD prescriptions.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer.

Placental single cell transcriptomics: Opportunities for endocrine disrupting chemical toxicology.

The placenta performs essential biologic functions for fetal development throughout pregnancy. Placental dysfunction is at the root of multiple adverse birth outcomes such as intrauterine growth restriction, preeclampsia, and preterm birth. Exposure to endocrine disrupting chemicals during pregnancy can cause placental dysfunction, and many prior human studies have examined molecular changes in bulk placental tissues.

Disparities with influenza vaccine use in long-term survivors of metastatic breast cancer.

Purpose: Elderly women diagnosed with metastatic breast cancer (MBC) are living longer, however their primary care management may be sub-optimal. Influenza results in preventable hospitalizations and deaths. Guidelines recommend the influenza vaccine for those > 65 years and those with cancer but use is unknown.

Trichloroethylene Metabolite -(1,2-Dichlorovinyl)-l-cysteine Stimulates Changes in Energy Metabolites and Amino Acids in the BeWo Human Placental Trophoblast Model during Syncytialization.

Syncytialization, the fusion of cytotrophoblasts into an epithelial barrier that constitutes the maternal-fetal interface, is a crucial event of placentation. This process is characterized by distinct changes to amino acid and energy metabolism. A metabolite of the industrial solvent trichloroethylene (TCE), -(1,2-dichlorovinyl)-l-cysteine (DCVC), modifies energy metabolism and amino acid abundance in HTR-8/SVneo extravillous trophoblasts.

Placental Cell Conditioned Media Modifies Hematopoietic Stem Cell Transcriptome In Vitro.

Background: Hematopoietic stem cells are cells that differentiate into all blood cell types. Although the placenta secretes hormones, proteins and other factors important for maternal and fetal health, cross-talk between placental cells and hematopoietic stem cells is poorly understood. Moreover, toxicant impacts on placental-hematopoietic stem cell communication is understudied.

Implementation of Systematic Financial Screening in an Outpatient Breast Oncology Setting.

Purpose: Implementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center.

Methods: We developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry.

Placental cell type deconvolution reveals that cell proportions drive preeclampsia gene expression differences.

The placenta mediates adverse pregnancy outcomes, including preeclampsia, which is characterized by gestational hypertension and proteinuria. Placental cell type heterogeneity in preeclampsia is not well-understood and limits mechanistic interpretation of bulk gene expression measures. We generated single-cell RNA-sequencing samples for integration with existing data to create the largest deconvolution reference of 19 fetal and 8 maternal cell types from placental villous tissue (n = 9 biological replicates) at term (n = 40,494 cells).

Advancing Survivors Knowledge (ASK Study) of Skin Cancer Surveillance After Childhood Cancer: A Randomized Controlled Trial in the Childhood Cancer Survivor Study.

Purpose: To improve skin cancer screening among survivors of childhood cancer treated with radiotherapy where skin cancers make up 58% of all subsequent neoplasms. Less than 30% of survivors currently complete recommended skin cancer screening.

Patients And Methods: This randomized controlled comparative effectiveness trial evaluated patient and provider activation (PAE + MD) patient and provider activation with teledermoscopy (PAE + MD + TD) compared with patient activation alone (PAE), which included print materials, text messaging, and a website on skin cancer risk factors and screening behaviors.

Changes in COVID-19 Vaccine Intent Among a Diverse Population of Older Adults, June 2021-February 2022.

Introduction COVID-19 vaccination rates remain suboptimal in the United States. Clinicians and policymakers need to better understand how likely vaccine-hesitant individuals are to ultimately accept vaccination and what is associated with such changes. This study's aims were to 1) describe changes between vaccine intentions and actual uptake from June 2021 through February 2022, and 2) identify modifiable factors associated with vaccine uptake among those with initial hesitancy.

Impact of a Hospital-Based Specialty Pharmacy in Partnership With a Care Coordination Organization on Time to Delivery and Receipt of Oral Anticancer Drugs.

Purpose: Oral anticancer drug (OACD) prescriptions require extensive coordination between providers and payers, which can delay drug receipt. Specialty pharmacies facilitate communication between multiple entities. In 2018, our cancer center partnered with a freestanding organization to implement a hospital-based specialty pharmacy (HB-SP).

Sexually concordant and dimorphic transcriptional responses to maternal trichloroethylene and/or N-acetyl cysteine exposure in Wistar rat placental tissue.

Numerous Superfund sites are contaminated with the volatile organic chemical trichloroethylene (TCE). In women, exposure to TCE in pregnancy is associated with reduced birth weight. Our previous study reported that TCE exposure in pregnant rats decreased fetal weight and elevated oxidative stress biomarkers in placentae, suggesting placental injury as a potential mechanism of TCE-induced adverse birth outcomes.

Dostarlimab for recurrent mismatch repair-deficient endometrial cancer: A cost-effectiveness study.

Objective: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy.