Bioethics and Medical Ethics Commons^™

Actionability Of Unanticipated Monogenic Disease Risks In Newborn Genomic Screening: Findings From The Babyseq Project, Robert C Green, Nidhi Shah, Casie A Genetti, Timothy Yu, Bethany Zettler, Melissa K Uveges, Ozge Ceyhan-Birsoy, Matthew S Lebo, Stacey Pereira, Pankaj B Agrawal, Richard B Parad, Amy L Mcguire, Kurt D Christensen, Talia S Schwartz, Heidi L Rehm, Ingrid A Holm, Alan H Beggs

Center for Medical Ethics and Health Policy Staff Publications

Newborn genomic sequencing (NBSeq) to screen for medically important genetic information is of considerable interest but data characterizing the actionability of such findings, and the downstream medical efforts in response to discovery of unanticipated genetic risk variants, are lacking. From a clinical trial of comprehensive exome sequencing in 127 apparently healthy infants and 32 infants in intensive care, we previously identified 17 infants (10.7%) with unanticipated monogenic disease risks (uMDRs). In this analysis, we assessed actionability for each of these uMDRs with a modified ClinGen actionability semiquantitative metric (CASQM) and created radar plots representing degrees of penetrance of the condition, …

Tissue Mass Spectrometry: How Solid Is Our Future?, Daisy Unsihuay, William S Phipps, Amanda G Paulovich, Jessica R Chapman, Axel Ducret, Livia S Eberlin, Jeffrey M Spraggins, Richard J A Goodwin

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Physician-Investigator, Research Coordinator, And Patient Perspectives On Dual-Role Consent In Oncology: A Qualitative Study, Stephanie R Morain, Dorit Barlevy, Steven Joffe, Emily A Largent

Center for Medical Ethics and Health Policy Staff Publications

Importance: Classic statements of research ethics generally advise against dual-role consent in which physician-investigators seek consent for research participation from patients with whom they have preexisting treatment relationships. Yet dual-role consent is common in clinical oncology research, as studies are often conducted in close relationship with clinical care.

Objective: To explore key stakeholders' perspectives on dual-role consent in clinical oncology trials.

Design, setting, and participants: This qualitative study with 43 participants was conducted at a National Cancer Institute-designated comprehensive cancer center from 2018 to 2022. Semistructured qualitative interviews of physician-investigators, research coordinators, and patients were performed. Respondents were recruited from …

Mindfulness And Cognitive Emotion Regulation In Pediatric Misophonia, Samuel D Spencer, Andrew G Guzick, Matti Cervin, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Misophonia is characterized by decreased tolerance of ordinary human-generated trigger sounds and associated visual stimuli (e.g., chewing, sniffing, lip smacking), coupled with intense affective reactions. The disorder often begins during childhood or adolescence and is associated with impairment and distress in numerous life domains. Research has begun to examine the underlying psychological mechanisms of misophonia in adults, but studies in youth are limited. Trait mindfulness (i.e., nonjudgmental and nonavoidant present-moment awareness) and cognitive emotion regulation (i.e., cognitive processing, or responding to, emotionally arousing situations) are two proposed mechanisms that may underpin pediatric misophonia and associated functional impairment. In the present …

Cognitive Behavioral Therapy For Children And Adolescents With Anxiety Disorders, Jordan T Stiede, Erika S Trent, Andres G Viana, Andrew G Guzick, Eric A Storch, Jonathan Hershfield

Center for Medical Ethics and Health Policy Staff Publications

Anxiety disorders are the most common class of psychiatric conditions among children and adolescents. The cognitive behavioral model of childhood anxiety has a strong theoretic and empirical foundation that provides the basis for effective treatment. Cognitive behavioral therapy (CBT), with an emphasis on exposure therapy, is the gold standard treatment for childhood anxiety disorders, with strong empirical support. A case vignette demonstrating CBT for childhood anxiety disorders in practice, as well as recommendations for clinicians, are also provided.

Child And Adolescent Psychiatrists’ Use, Attitudes, And Understanding Of Genetic Testing And Pharmacogenetics In Clinical Practice, Takahiro Soda, Amanda R Merner, Brent J Small, Laura N Torgerson, Katrina Muñoz, Jehannine Austin, Eric A Storch, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

The purpose of this study was to report current practices and attitudes of child and adolescent psychiatrists (CAP) regarding diagnostic genetic and pharmacogenetic (PGx) testing. We surveyed 958 US-based practicing CAP. 54.9% of respondents indicated that they had ordered/referred for a genetic test in the past 12 months. 87% of respondents agreed that it is their role to discuss genetic information regarding psychiatric conditions with their patients; however, 45% rated their knowledge of genetic testing practice guidelines as poor/very poor. The most ordered test was PGx (32.2%), followed by chromosomal microarray (23.0%). 73.4% reported that PGx is at least slightly …

Withdrawing Extra Corporeal Membrane Oxygenation (Ecmo) Against A Family’S Wishes: Three Permissible Scenarios, Trevor M Bibler, Asma Zainab

Center for Medical Ethics and Health Policy Staff Publications

The ethical permissibility of unilaterally withdrawing life-sustaining technologies has been a perennial topic in transplant and critical care medicine, often focusing on CPR and mechanical ventilation. The permissibility of unilateral withdrawal of extracorporeal membrane oxygenation (ECMO) has been discussed sparingly. When addressed, authors have appealed to professional authority rather than substantive ethical analysis. In this Perspective, we argue that there are at least three (3) scenarios wherein healthcare teams would be justified in unilaterally withdrawing ECMO, despite the objections of the patient's legal representative. The ethical considerations that provide the groundwork for these scenarios are, primarily: equity, integrity, and the …

Ethical, Legal, And Social Implications Of Genomics Research: Implications For Building A More Racially Diverse Bioethics Workforce, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Child And Adolescent Psychiatrists’ Use, Attitudes, And Understanding Of Genetic Testing And Pharmacogenetics In Clinical Practice, Takahiro Soda, Amanda R Merner, Brent J Small, Laura N Torgerson, Katrina Muñoz, Jehannine Austin, Eric A Storch, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

The purpose of this study was to report current practices and attitudes of child and adolescent psychiatrists (CAP) regarding diagnostic genetic and pharmacogenetic (PGx) testing. We surveyed 958 US-based practicing CAP. 54.9% of respondents indicated that they had ordered/referred for a genetic test in the past 12 months. 87% of respondents agreed that it is their role to discuss genetic information regarding psychiatric conditions with their patients; however, 45% rated their knowledge of genetic testing practice guidelines as poor/very poor. The most ordered test was PGx (32.2%), followed by chromosomal microarray (23.0%). 73.4% reported that PGx is at least slightly …

Call For Moral Recognition As Part Of Paediatric Assent, Jared Smith, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Cancerhervdb: Human Endogenous Retrovirus (Herv) Expression Database For Human Cancer Accelerates Studies Of The Retrovirome And Predictions For Herv-Based Therapies, Erik Stricker, Erin C Peckham-Gregory, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

In this study, we sought to create a database summarizing the expression of human endogenous retroviruses (HERVs) in various human cancers. HERVs are suitable therapeutic targets due to their abundance in the human genome, overexpression in various malignancies, and involvement in various cancer pathways. We identified articles on HERVs from PubMed and then prescreened and automatically categorized them using the portable document format (PDF) data extractor (PDE) R package. We discovered 196 primary research articles with HERV expression data from cancer tissues or cancer cell lines. HERV RNA and protein expression was reported in brain, breast, cervical, colorectal, endocrine, gastrointestinal, …

An Integrated Isothermal Nucleic Acid Amplification Test To Detect Hpv16 And Hpv18 Dna In Resource-Limited Settings, Kathryn A Kundrod, Maria Barra, Alexis Wilkinson, Chelsey A Smith, Mary E Natoli, Megan M Chang, Jackson B Coole, Akshaya Santhanaraj, Cesaltina Lorenzoni, Celda Mavume, Hira Atif, Jane Richards Montealegre, Michael E Scheurer, Philip E Castle, Kathleen M Schmeler, Rebecca R Richards-Kortum

Center for Medical Ethics and Health Policy Staff Publications

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce …

Cervical Cancer Screening Among English- And Spanish-Speaking Hispanic Women In An Urban Safety Net Health System, 2015–2020, Trisha L Amboree, Susan Lackey Parker, Shaun Bulsara, Matthew L Anderson, Kathleen M Schmeler, Elizabeth Y Chiao, Jane R Montealegre

Center for Medical Ethics and Health Policy Staff Publications

Background: The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system.

Methods: Electronic health records were used to identify 46,094 women aged 30-65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test.

Results: Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: …

“Handicap Removed”: An Alternative Path To The Social Model, Craig M. Rustici

Journal of Gender, Ethnic, and Cross-Cultural Studies

This article identifies an expression of a social model of disability in a 1966 film promoting Hofstra University’s Program for the Higher Education of the Handicapped and traces that model back to books published by the pioneering rehabilitation physician Henry H. Kessler in 1935 and 1947, decades before the UPIAS (Union of the Physically Impaired against Segregation) Fundamental Principles of Disability (1976). In light of Kessler’s articulation of social and minority models, identification of contrasting religious, charity and medical models, and discussion of disability stigma, this article reassesses Ruth O’Brien’s critique, in Crippled Justice (2001), of Kessler and the twentieth-century …

Modeling The Longitudinal Changes Of Ancestry Diversity In The Million Veteran Program, Frank R Wendt, Gita A Pathak, Jacqueline Vahey, Xuejun Qin, Dora Koller, Brenda Cabrera-Mendoza, Angela Haeny, Kelly M Harrington, Nallakkandi Rajeevan, Linh M Duong, Daniel F Levey, Flavio De Angelis, Antonella De Lillo, Tim B Bigdeli, Saiju Pyarajan, John Michael Gaziano, Joel Gelernter, Mihaela Aslan, Dawn Provenzale, Drew A Helmer, Elizabeth R Hauser, Renato Polimanti, Department Of Veteran Affairs Cooperative Study Program (#2006)

Center for Medical Ethics and Health Policy Staff Publications

Background: The Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic changes over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). To investigate these aspects, we divided MVP participants into five birth cohorts (N-range = 123,888 [born from 1943 to 1947] to 136,699 [born from 1948 to 1953]).

Results: Ancestry groups were defined by (i) HARE (harmonized ancestry and race/ethnicity) and (ii) a random-forest clustering approach using the 1000 Genomes Project and …

Black Bioethics In The Age Of Black Lives Matter, Keisha Ray, Faith E Fletcher, Daphne O Martschenko, Jennifer E James

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Correction To: Black Bioethics In The Age Of Black Lives Matter, Keisha Ray, Faith E Fletcher, Daphne O Martschenko, Jennifer E James

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Divergent Clinical Presentations And Outcomes Among Children And Adolescents With Kaposi Sarcoma In Malawi And Tanzania, Liane R Campbell, Allison Silverstein, Erin Peckham-Gregory, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Jason M Bacha, Carrie L Kovarik, Parth S Mehta, Toni Chanroo, Asulwisye Kapesa, Beatrice Malingoti, Rizine Mzikamanda, Nmazuo W Ozuah, Carl E Allen, Michael E Scheurer, Nader K El-Mallawany

Center for Medical Ethics and Health Policy Staff Publications

Objectives: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach.

Methods: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania.

Results: …

Expanding Narrative Medicine Through The Collaborative Construction And Compelling Performance Of Stories, Woods Nash, Mgbechi Erondu, Andrew Childress

Center for Medical Ethics and Health Policy Staff Publications

This essay proposes an expansion of the concept of narrative competence, beyond close reading, to include two more skills: the collaborative construction and compelling performance of stories. To show how this enhanced form of narrative competence can be attained, the essay describes Off Script, a cocurricular medical storytelling program with three phases: 1) creative writing workshop, 2) dress rehearsal, and 3) public performance of stories. In these phases, Off Script combines literary studies, creative writing, reflective practice, collegial feedback, and drama. With increased narrative competence, Off Script participants are likely better equipped to engage in more impactful health advocacy and …

Ethical Hazards Of Health Data Governance In The Metaverse, Kristin Kostick-Quenet, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Metaverse-enabled healthcare is no longer hypothetical. Developers must now contend with ethical, legal and social hazards if they are to overcome the systematic inefficiencies and inequities that exist for patients who seek care in the real world.

Framing The Family: A Qualitative Exploration Of Factors That Shape Family-Level Experience Of Pediatric Genomic Sequencing, Hadley Stevens Smith, Emily S Bonkowski, Madison R Hickingbotham, Raymond Belanger Deloge, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS …

Framing The Family: A Qualitative Exploration Of Factors That Shape Family-Level Experience Of Pediatric Genomic Sequencing, Hadley Stevens Smith, Emily S Bonkowski, Madison R Hickingbotham, Raymond Belanger Deloge, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS …

International Society For Prenatal Diagnosis 2022 Debate 3-Fetal Genome Sequencing Should Be Offered To All Pregnant Patients, Ignatia B Van Den Veyver, Yuval Yaron, Zandra C Deans

Center for Medical Ethics and Health Policy Staff Publications

Prenatal trio exome sequencing (ES) has become integrated into the care for pregnant women when the fetus has structural anomalies. Details regarding optimizing indications for prenatal exome sequencing, its detection rates with different categories of fetal anomalies, and principles of interpretation of pathogenicity of sequence variants are still under investigation. However, there is now growing consensus about its benefits for finding the cause of fetal structural anomalies. What is not established, is whether exome or genome sequencing (GS) has a place in the care of all pregnant women. This report is a summary of the debate on this topic at …

Things That Make You Go Hmm: Myths And Misconceptions Within Cognitive-Behavioral Treatment Of Obsessive-Compulsive Disorder, Samuel D Spencer, Jordan T Stiede, Andrew D Wiese, Andrew G Guzick, Matti Cervin, Dean Mckay, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

The past four decades have yielded a robust body of evidence supporting the efficacy and effectiveness of cognitive-behavioral therapy (CBT) as a gold-standard treatment for obsessive-compulsive disorder (OCD) across the lifespan. Exposure and response prevention (E/RP) has been identified as a key component of this approach. Despite robust research support for CBT with E/RP, several myths and misconceptions continue to proliferate in both research and practice settings. Such myths and misconceptions are concerning, as they lack empirical basis, may hinder widespread dissemination and implementation of CBT for OCD, and run contrary to the practice of evidence-based psychological medicine. Focusing on …

Development And Pilot Testing Of Internet-Delivered, Family-Based Cognitive Behavioral Therapy For Anxiety And Obsessive-Compulsive Disorders In Autistic Youth, Andrew G Guzick, Sophie C Schneider, Amanda B Perozo Garcia, Minjee Kook, Rebecca L Greenberg, David Riddle, Morgan Mcneel, Servando Rodriguez-Barajas, Michelle Yang, Blake Upshaw, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Cognitive behavioral therapy adapted for autistic youth with anxiety and/or OCD has a strong evidence base, but few have access. A 12-week family-based, Internet-delivered cognitive behavioral therapy (iCBT) program for 7-15 year-old autistic youth with anxiety and/or OCD was developed as a potential method to address this problem. Quantitative and qualitative feedback from stakeholders (parents, youth, clinicians) was gathered on an initial draft of content before conducting a pilot trial. This feedback suggested high quality, engagement, usability, and informativeness of the material. Suggestions were incorporated into the treatment program that was tested in a pilot trial. Eight families were randomized …

Are Human Papillomavirus Knowledge And Vaccine Uptake Associated With Hiv Status And Social Determinants Of Health In Young Sexual Minority Men?, Trisha L Amboree, Alan G Nyitray, John Schneider, Nick Gargurevich, Jacky Kuo, Elizabeth Y Chiao, Lu-Yu Hwang, Kayo Fujimoto

Center for Medical Ethics and Health Policy Staff Publications

This brief report examines the relationship, if any, between human immunodeficiency virus (HIV) status, and individual-level and socio-sexual partner-level factors of social determinants of health (SDOH) that are associated with human papillomavirus (HPV) knowledge and vaccine uptake in young sexual minority men (YSMM). We used data from 126 YSMM recruited by network-based sampling during 2015-2016 in Houston, Texas. Descriptive statistics and regression analyses were conducted to test the association between HIV status, SDOH, and HPV knowledge and vaccine uptake. Those living with HIV had lower odds of knowledge of HPV-associated anal cancer (OR: 0.43, 95% CI: 0.18-0.97) and knowledge of …

Key Drivers Of Family-Level Utility Of Pediatric Genomic Sequencing: A Qualitative Analysis To Support Preference Research, Hadley Stevens Smith, Emily S Bonkowski, Raymond Belanger Deloge, Amanda M Gutierrez, Alva M Recinos, Tara A Lavelle, David L Veenstra, Amy L Mcguire, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Given that pediatric genomic sequencing (GS) may have implications for the health and well-being of both the child and family, a clearer understanding of the key drivers of the utility of GS from the family perspective is needed. The purpose of this study is to explore what is important to caregivers of pediatric patients regarding clinical GS, with a focus on family-level considerations. We conducted semi-structured interviews with caregivers (n = 41) of pediatric patients who had been recommended for or completed GS that explored the scope of factors caregivers considered when deciding whether to pursue GS for their child. …

Hervs And Cancer-A Comprehensive Review Of The Relationship Of Human Endogenous Retroviruses And Human Cancers, Erik Stricker, Erin C Peckham-Gregory, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV …

Parents’ Decision-Making Regarding Whether To Receive Adult-Onset Only Genetic Findings For Their Children: Findings From The Babyseq Project, Stacey Pereira, Amanda M Gutierrez, Jill Oliver Robinson, Kurt D Christensen, Casie A Genetti, Carrie L Blout Zawatsky, Rebecca L Hsu, Bethany Zettler, Melissa Kurtz Uveges, Richard B Parad, Alan H Beggs, Ingrid A Holm, Robert C Green, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Most professional guidelines recommend against genetic screening for adult-onset only (AO) conditions until adulthood, yet others argue that there may be benefit to disclosing such results. We explored parents' decision-making on this issue in the BabySeq Project, a clinical trial of newborn genomic sequencing.

Methods: We conducted interviews with parents (N = 24) who were given the option to receive actionable AO results for their children. Interviews explored parents' motivations to receive and reasons to decline AO genetic disease risk information, their decision-making process, and their suggestions for supporting parents in making this decision.

Results: Parents noted several motivations …

Replication Competent Retrovirus Testing (Rcr) In The National Gene Vector Biorepository: No Evidence Of Rcr In 1,595 Post-Treatment Peripheral Blood Samples Obtained From 60 Clinical Trials, Kenneth Cornetta, Jing Yao, Kimberley House, Lisa Duffy, Prasad S Adusumilli, Rachel Beyer, Claire Booth, Malcolm Brenner, Kevin Curran, Bambi Grilley, Helen Heslop, Christian S Hinrichs, Rosandra N Kaplan, Hans-Peter Kiem, James Kochenderfer, Donald B Kohn, Sham Mailankody, Scott M Norberg, Roisin E O'Cearbhaill, Jennifer Pappas, Jae Park, Carlos Ramos, Antonio Ribas, Isabelle Rivière, Steven A Rosenberg, Craig Sauter, Nirali N Shah, Susan F Slovin, Adrian Thrasher, David A Williams, Tsai-Yu Lin

Center for Medical Ethics and Health Policy Staff Publications

The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far …