Bioethics and Medical Ethics Commons^™

Comparing Visualization Performance Of Liquid Embolic Agents Using A Novel Injectable Phantom, J Ryan Mason, Cristina Dodge, Adam Beardsley, Susan Hilsenbeck, Goetz Benndorf

Center for Medical Ethics and Health Policy Staff Publications

Background: Radiographic visualization of liquid embolic agents (LEAs) during embolization procedures in neurovascular territory represents a crucial feature to ensure efficacy and safety for the patients during endovascular treatment of arteriovenous shunting lesions. Radiopacity of available LEAs varies significantly and limited methods are currently available for comparison. The purpose of this study was to compare the contrast resolution (CR) during injection under blank roadmap of various LEAs, as well as standard contrast material.

Methods: An injectable angiographic phantom was designed consisting of parallel tubings between 313 and 1000 micron. Under roadmap, eight radiopaque liquid agents were injected and analyzed: Onyx18®, …

What Is The Economic Benefit Of Annual Covid-19 Vaccination From The Adult Individual Perspective?, Sarah M Bartsch, Kelly J O'Shea, Colleen Weatherwax, Ulrich Strych, Kavya Velmurugan, Danielle C John, Maria Elena Bottazzi, Mustafa Hussein, Marie F Martinez, Kevin L Chin, Allan Ciciriello, Jessie Heneghan, Alexis Dibbs, Sheryl A Scannell, Peter J Hotez, Bruce Y Lee

Center for Medical Ethics and Health Policy Staff Publications

Background: With coronavirus disease 2019 (COVID-19) vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward.

Methods: We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine.

Results: For an 18-49 year old, getting vaccinated at its current price ($60) can save the individual on average $30-$603 if the individual is uninsured and $4-$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe …

A Systematic Review Of Racial Disparities In Emergency Department Pain Evaluation And Treatment In The United States, Cyrus Wolff

Theses and Graduate Projects

Background: Providers working in emergency departments (ED) must balance the need to relieve patients’ pain with the dangers of overprescribing opioids. Lack of standardization of pain evaluation and treatment may contribute to inequities in the management of pain in emergency departments. Evaluating differences in how different populations receive care in emergency departments can help to identify problems and areas where improvements need to occur.

Purpose: The purpose of this literature review is to evaluate what current research states about the prevalence and causes of racial disparities in pain evaluation and treatment in United States emergency departments and determine what gaps …

This Is A Call To Action For All Primary Care Providers: Do Better For Your Transgender Patients, Kate Castor

Theses and Graduate Projects

Background: Patients of all ages benefit from primary care. However, not everyone has equal access to primary care. Transgender patients often face a multitude of barriers to receiving basic healthcare.

Purpose: Improve health outcomes for transgender patients, enlighten providers on significant disparities, and offer solutions to these disparities faced by transgender community in the healthcare setting and when receiving cancer screening.

Methods: Literature review comprising results from Augsburg University Lindell Library databases, American Journal of Medicine, and Google Scholar.

Conclusions: Everyone can do better for their transgender patients, but primary care providers should take extra care cultivating relationships with these …

The Ethical Duty Of Care For Suicide Ideation, Tah Ngijoi Yogo

Electronic Theses and Dissertations

With suicide being a leading global cause of death, there is a need to explore the ethical complexities surrounding suicide and preventive measures. This dissertation questions the morality of suicide by examining the historical and philosophical dimensions across cultures and religions. The text argues for an approach that acknowledges rational suicide while developing the ethics of paternalistic measures for suicide prevention of vulnerable populations.

Considering the ethics of autonomy, the dissertation discusses the practice of nudging in healthcare to highlight the role of paternalism in supporting informed consent. The text proposes an enhanced autonomy model that balances trust, influence, and …

Phase I Trial Of Gd2cart Cells Augmented With Constitutive Interleukin-7 Receptor For Treatment Of High-Grade Pediatric Cns Tumors, Frank Y Lin, Austin Stuckert, Candise Tat, Mark White, Lucia Ruggieri, Huimin Zhang, Birju Mehta, Natalia Lapteva, Zhuyong Mei, Angela Major, Sachin Thakkar, Thomas Shum, Kathan Parikh, Meng-Fen Wu, Holly B Lindsay, Lauren Scherer, Meghan Shekar, Patricia Baxter, Tao Wang, Bambi Grilley, Karen Moeller, John Hicks, Angshumoy Roy, Jamie Anastas, Fatema Malbari, Guillermo Aldave, Murali Chintagumpala, Susan Blaney, D Williams Parsons, Malcolm K Brenner, Helen E Heslop, Cliona M Rooney, Bilal Omer

Center for Medical Ethics and Health Policy Staff Publications

Purpose: T cells modified with chimeric antigen receptors (CARTs) have demonstrated efficacy for hematologic malignancies; however, benefit for patients with CNS tumors has been limited. To enhance T cell activity against GD2+ CNS malignancies, we modified GD2-directed CART cells (GD2.CARTs) with a constitutively active interleukin (IL)-7 receptor (C7R-GD2.CARTs).

Methods: Patients age 1-21 years with H3K27-altered diffuse midline glioma (DMG) or other recurrent GD2-expressing CNS tumors were eligible for this phase I trial (ClinicalTrials.gov identifier: NCT04099797). All subjects received standard-of-care adjuvant radiation therapy or chemotherapy before study enrollment. The first treatment cohort received GD2.CARTs alone (1 × 107 cells/m2), and …

Taking Chances: Plagiarism In Manuscripts, Richard Alweis

Advances in Clinical Medical Research and Healthcare Delivery

The Editor-in-Chief reflects on why authors plagiarize after the journal received several manuscripts containing plagiarized work.

Phase Ii Study Of Vemurafenib In Children And Young Adults With Tumors Harboring Braf V600 Mutations: Nci-Cog Pediatric Match Trial (Apec1621) Arm G, Marie V Nelson, Aerang Kim, P Mickey Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent D Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Nilsa C Ramirez, Alok Jaju, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D Williams Parsons

Center for Medical Ethics and Health Policy Staff Publications

Background: This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations.

Methods: Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib.

Results: Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to …

Measuring Perceived Utility Of Genomic Sequencing: Development And Validation Of The Genetic Utility (Gene-U) Scale For Pediatric Diagnostic Testing, Hadley Stevens Smith, Caryn Kseniya Rubanovich, Jill Oliver Robinson, Ariel N Levchenko, Sarah A Classen, Janet Malek, Barbara Biesecker, Kyle B Brothers, Benjamin S Wilfond, Christine Rini, Sara J Knight, Amy L Mcguire, Cinnamon S Bloss

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Measuring the effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents' perceived utility of pediatric diagnostic GS.

Methods: Informed by a 5-domain conceptual model, the study comprised 5 steps: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Parents of pediatric patients who had received results of clinically indicated GS participated in structured cognitive interviews and 2 rounds of surveys. After eliminating items based on theory and quantitative performance, we conducted …

Expanding A Behavioral View On Digital Health Access: Drivers And Strategies To Promote Equity, Maura M Kepper, Lauren A Fowler, Isabelle S Kusters, Jean W Davis, Manal Baqer, Sara Sagui-Henson, Yunyu Xiao, Adati Tarfa, Jean C Yi, Bryan Gibson, Kristin E Heron, Nicole M Alberts, Marissa Burgermaster, Veronica Ps Njie-Carr, Lisa M Klesges

Center for Medical Ethics and Health Policy Staff Publications

The potential and threat of digital tools to achieve health equity has been highlighted for over a decade, but the success of achieving equitable access to health technologies remains challenging. Our paper addresses renewed concerns regarding equity in digital health access that were deepened during the COVID-19 pandemic. Our viewpoint is that (1) digital health tools have the potential to improve health equity if equitable access is achieved, and (2) improving access and equity in digital health can be strengthened by considering behavioral science-based strategies embedded in all phases of tool development. Using behavioral, equity, and access frameworks allowed for …

Governing With Public Engagement: An Anticipatory Approach To Human Genome Editing, Dorit Barlevy, Eric Juengst, Jeffrey Kahn, Jonathan Moreno, Lauren Lambert, Alta Charo, Hervé Chneiweiss, Mahmud Farooque, David H Guston, Insoo Hyun, Paul S Knoepfler, Cynthia Selin, Rebecca Wilbanks, Manar Zaghlula, Christopher Thomas Scott

Center for Medical Ethics and Health Policy Staff Publications

In response to calls for public engagement on human genome editing (HGE), which intensified after the 2018 He Jiankui scandal that resulted in the implantation of genetically modified embryos, we detail an anticipatory approach to the governance of HGE. By soliciting multidisciplinary experts’ input on the drivers and uncertainties of HGE development, we developed a set of plausible future scenarios to ascertain publics values—specifically, their hopes and concerns regarding the novel technology and its applications. In turn, we gathered a subset of multidisciplinary experts to propose governance recommendations for HGE that incorporate identified publics’ values. These recommendations include: (1) continued …

Generating Clinical-Grade Gene-Disease Validity Classifications Through The Clingen Data Platforms, Matt W Wright, Courtney L Thaxton, Tristan Nelson, Marina T Distefano, Juliann M Savatt, Matthew H Brush, Gloria Cheung, Mark E Mandell, Bryan Wulf, T J Ward, Scott Goehringer, Terry O'Neill, Phil Weller, Christine G Preston, Ingrid M Keseler, Jennifer L Goldstein, Natasha T Strande, Jennifer Mcglaughon, Danielle R Azzariti, Ineke Cordova, Hannah Dziadzio, Lawrence Babb, Kevin Riehle, Aleksandar Milosavljevic, Christa Lese Martin, Heidi L Rehm, Sharon E Plon, Jonathan S Berg, Erin R Riggs, Teri E Klein

Center for Medical Ethics and Health Policy Staff Publications

Clinical genetic laboratories must have access to clinically validated biomedical data for precision medicine. A lack of accessibility, normalized structure, and consistency in evaluation complicates interpretation of disease causality, resulting in confusion in assessing the clinical validity of genes and genetic variants for diagnosis. A key goal of the Clinical Genome Resource (ClinGen) is to fill the knowledge gap concerning the strength of evidence supporting the role of a gene in a monogenic disease, which is achieved through a process known as Gene-Disease Validity curation. Here we review the work of ClinGen in developing a curation infrastructure that supports the …

How To Design Equitable Digital Health Tools: A Narrative Review Of Design Tactics, Case Studies, And Opportunities, Amy Bucher, Beenish M Chaudhry, Jean W Davis, Katharine Lawrence, Emily Panza, Manal Baqer, Rebecca T Feinstein, Sherecce A Fields, Jennifer Huberty, Deanna M Kaplan, Isabelle S Kusters, Frank T Materia, Susanna Y Park, Maura Kepper

Center for Medical Ethics and Health Policy Staff Publications

With a renewed focus on health equity in the United States driven by national crises and legislation to improve digital healthcare innovation, there is a need for the designers of digital health tools to take deliberate steps to design for equity in their work. A concrete toolkit of methods to design for health equity is needed to support digital health practitioners in this aim. This narrative review summarizes several health equity frameworks to help digital health practitioners conceptualize the equity dimensions of importance for their work, and then provides design approaches that accommodate an equity focus. Specifically, the Double Diamond …

Genomic Sequencing Research In Pediatric Cancer Care: Decision Making, Attitudes, And Perceived Utility Among Adolescents And Young Adults And Their Parents, Amanda M Gutierrez, Jill O Robinson, Hadley S Smith, Lauren R Desrosiers-Battu, Sarah R Scollon, Isabel Canfield, Rebecca L Hsu, Nicole M Schneider, D Williams Parsons, Sharon E Plon, Wendy Allen-Rhoades, Mary A Majumder, Janet Malek, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Professional guidelines recommend engaging adolescents and young adults (AYAs) in medical decision making (DM), including whether to undergo genomic sequencing (GS). We explored DM around GS and attitudes after return of GS results among a diverse group of AYAs with cancer and their parents.

Methods: We surveyed AYAs with cancer (n = 75) and their parents (n = 52) 6 months after receiving GS results through the Texas KidsCanSeq study. We analyzed AYAs' DM role in GS research enrollment and their satisfaction with that role. We compared AYAs' and parents' self-reported understanding of, attitudes toward, and perceived utility of …

Large-Scale Genotype Prediction From Rna Sequence Data Necessitates A New Ethical And Policy Framework, Mary A Majumder, Jeffrey T Leek, Kasper D Hansen, Afrooz Razi, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Genotype prediction from RNA-seq data has become widespread. RNA-seq data, unlike DNA-seq data, are available as raw reads for many projects, with related protocols and consent terms typically inaccessible. However, there is a lack of clarity in current policy and inconsistency in practice with regard to the handling of these data. Here, we call for a framework for management of RNA-seq data and the predicted genotypes that includes registered access for RNA-seq data, controlled access for predicted genotypes, and a code of conduct for data access and use, as well as enhanced downstream protections.

Trust Criteria For Artificial Intelligence In Health: Normative And Epistemic Considerations, Kristin Kostick-Quenet, Benjamin H Lang, Jared Smith, Meghan Hurley, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Rapid advancements in artificial intelligence and machine learning (AI/ML) in healthcare raise pressing questions about how much users should trust AI/ML systems, particularly for high stakes clinical decision-making. Ensuring that user trust is properly calibrated to a tool's computational capacities and limitations has both practical and ethical implications, given that overtrust or undertrust can influence over-reliance or under-reliance on algorithmic tools, with significant implications for patient safety and health outcomes. It is, thus, important to better understand how variability in trust criteria across stakeholders, settings, tools and use cases may influence approaches to using AI/ML tools in real settings. As …

Chimeric Antigen Receptor-Induced Antigen Loss Protects Cd5cart Cells From Fratricide Without Compromising On-Target Cytotoxicity, Royce Ma, Mae Woods, Phillip Burkhardt, Noah Crooks, Dayenne G Van Leeuwen, Daniil Shmidt, Jacob Couturier, Alexandre Chaumette, Divya Popat, Laquisa C Hill, Rayne H Rouce, Sachin Thakkar, Aaron F Orozco, Alexandre F Carisey, Malcolm K Brenner, Maksim Mamonkin

Center for Medical Ethics and Health Policy Staff Publications

Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage. We demonstrate that the expression of a chimeric antigen receptor (CAR) targeting CD5, a prominent pan-T cell antigen, induces rapid internalization and complete loss of the CD5 protein on T cells, protecting them from self-targeting. Notably, exposure of healthy and malignant T cells to CD5.CART cells induces similar internalization of CD5 on target cells, transiently shielding them from cytotoxicity. However, this protection is short-lived, as sustained activity of CD5.CART cells in patients with T cell malignancies results in full …

Impact Of Efavirenz On Hormone-Positive Breast Cancer Survival In Women Living With Hiv, Arthur T Johnson, Taolo Ntloedibe, Jose Euberto Mendez Reyes, Mogomotsi S Matshaba, Scott L Dryden-Peterson, Elizabeth Y Chiao

Center for Medical Ethics and Health Policy Staff Publications

Women living with HIV and breast cancer have poorer survival than HIV-negative women. Efavirenz-estrogen interactions are documented; however, the survival impact is unknown. Survival between women with estrogen-receptor positive breast cancer taking efavirenz (n = 38) and nonefavirenz regimens (n = 51) were compared. The 5-year overall-survival was 48.9% [95% confidence interval (CI) 33.0-72.2 and 51.1% (95% CI 34.0-76.8)] in the efavirenz and nonefavirenz groups, respectively suggesting efavirenz is unlikely driving poorer survival in women living with HIV and estrogen-receptor positive breast cancer.

The Impact Of Clinical Genome Sequencing In A Global Population With Suspected Rare Genetic Disease, Erin Thorpe, Taylor Williams, Chad Shaw, Evgenii Chekalin, Julia Ortega, Keisha Robinson, Jason Button, Marilyn C Jones, Miguel Del Campo, Donald Basel, Julie Mccarrier, Laura Davis Keppen, Erin Royer, Romina Foster-Bonds, Milagros M Duenas-Roque, Nora Urraca, Kerri Bosfield, Chester W Brown, Holly Lydigsen, Henry J Mroczkowski, Jewell Ward, Fabio Sirchia, Elisa Giorgio, Keith Vaux, Hildegard Peña Salguero, Aimé Lumaka, Gerrye Mubungu, Prince Makay, Mamy Ngole, Prosper Tshilobo Lukusa, Adeline Vanderver, Kayla Muirhead, Omar Sherbini, Melissa D Lah, Katelynn Anderson, Jeny Bazalar-Montoya, Richard S Rodriguez, Mario Cornejo-Olivas, Karina Milla-Neyra, Marwan Shinawi, Pilar Magoulas, Duncan Henry, Kate Gibson, Samuel Wiafe, Parul Jayakar, Daria Salyakina, Diane Masser-Frye, Arturo Serize, Jorge E Perez, Alan Taylor, Shruti Shenbagam, Ahmad Abou Tayoun, Alka Malhotra, Maren Bennett, Vani Rajan, James Avecilla, Andrew Warren, Max Arseneault, Tasha Kalista, Ali Crawford, Subramanian S Ajay, Denise L Perry, John Belmont, Ryan J Taft

Center for Medical Ethics and Health Policy Staff Publications

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds …

Olaparib For Childhood Tumors Harboring Defects In Dna Damage Repair Genes: Arm H Of The Nci-Cog Pediatric Match Trial, Julia L Glade Bender, Kerice Pinkney, Paul M Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent D Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Nilsa C Ramirez, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald W Parsons

Center for Medical Ethics and Health Policy Staff Publications

Background: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib.

Methods: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response.

Results: Eighteen patients matched …