Bioethics and Medical Ethics Commons^™

The Risks Of Birth Defects And Childhood Cancer With Conception By Assisted Reproductive Technology, Barbara Luke, Morton B Brown, Ethan Wantman, Maria J Schymura, Marilyn L Browne, Sarah C Fisher, Nina E Forestieri, Chandrika Rao, Hazel B Nichols, Mahsa M Yazdy, Susan T Gershman, Caitlin R Sacha, Melanie Williams, Mary K Ethen, Mark A Canfield, Kevin J Doody, Michael L Eisenberg, Valerie L Baker, Carrie Williams, Alastair G Sutcliffe, Melissa A Richard, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Study question: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer?

Summary answer: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects.

What is known already: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for …

Should Health Systems Share Genetic Findings With At-Risk Relatives When The Proband Is Deceased? Interviews With Individuals Diagnosed With Lynch Syndrome, Jessica Ezzell Hunter, Jennifer L. Schneider, Alison J. Firemark, James V. Davis, Sara Gille, Pamala A. Pawloski, Su-Ying Liang, Victoria Schlieder, Alanna Kulchak Rahm

Journal of Patient-Centered Research and Reviews

Purpose: Genetic information has health implications for patients and their biological relatives. Death of a patient before sharing a genetic diagnosis with at-risk relatives is a missed opportunity to provide important information that could guide interventions to minimize cancer-related morbidity and mortality in relatives.

Methods: We performed semi-structured interviews with individuals diagnosed with Lynch syndrome at 1 of 4 health systems to explore their perspectives on whether health systems should share genetic risk information with relatives following a patient’s death. An inductive, open-coding approach was used to analyze audio-recorded content, with software-generated code reports undergoing iterative comparative analysis by a …

Resident Perceptions Of The Short- And Long-Term Impacts Of Hurricane Harvey, Amal Rammah, Sheryl Mccurdy, Melissa Bondy, Abiodun O Oluyomi, Elaine Symanski

Center for Medical Ethics and Health Policy Staff Publications

Severe storms and flooding events are expected to increase in frequency and severity, with lasting economic, social, and psychological impacts on communities in post-disaster recovery. In the first mixed methods study to focus on the experiences of Houstonians during Hurricane Harvey, which resulted in unprecedented and widespread flooding and billions of dollars in damage, we conducted five focus groups from four neighborhoods almost two years after Harvey made landfall. Our purpose was to understand how residents withstood and recovered from flooding-related stressors, what the major sources of support were and what long-term issues they were still dealing with. Residents relied …

Mendelian Gene Identification Through Mouse Embryo Viability Screening, Pilar Cacheiro, Carl Henrik Westerberg, Jesse Mager, Mary E Dickinson, Lauryl M J Nutter, Violeta Muñoz-Fuentes, Chih-Wei Hsu, Ignatia B Van Den Veyver, Ann M Flenniken, Colin Mckerlie, Stephen A Murray, Lydia Teboul, Jason D Heaney, K C Kent Lloyd, Louise Lanoue, Robert E Braun, Jacqueline K White, Amie K Creighton, Valerie Laurin, Ruolin Guo, Dawei Qu, Sara Wells, James Cleak, Rosie Bunton-Stasyshyn, Michelle Stewart, Jackie Harrisson, Jeremy Mason, Hamed Haseli Mashhadi, Helen Parkinson, Ann-Marie Mallon, Damian Smedley

Center for Medical Ethics and Health Policy Staff Publications

Background: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property.

Methods: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous …

Measurement Of Severe Acute Respiratory Syndrome Coronavirus 2 Antigens In Plasma Of Pediatric Patients With Acute Coronavirus Disease 2019 Or Multisystem Inflammatory Syndrome In Children Using An Ultrasensitive And Quantitative Immunoassay, George B Sigal, Tanya Novak, Anu Mathew, Janet Chou, Yubo Zhang, Navaratnam Manjula, Pradeepthi Bathala, Jessica Joe, Nikhil Padmanabhan, Daniel Romero, Gabriella Allegri-Machado, Jill Joerger, Laura L Loftis, Stephanie P Schwartz, Tracie C Walker, Julie C Fitzgerald, Keiko M Tarquinio, Matt S Zinter, Jennifer E Schuster, Natasha B Halasa, Melissa L Cullimore, Aline B Maddux, Mary A Staat, Katherine Irby, Heidi R Flori, Bria M Coates, Hillary Crandall, Shira J Gertz, Adrienne G Randolph, Nira R Pollock, Overcoming Covid-19 Investigators

Center for Medical Ethics and Health Policy Staff Publications

Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery).

Methods: Plasma was collected from inpatients (< 21 years) enrolled across 15 hospitals in 15 US states. Acute COVID-19 patients (n = 36) had a range of disease severity and positive nasopharyngeal SARS-CoV-2 RT-PCR within 24 hours of blood collection. Patients with MIS-C (n = 53) met CDC criteria and tested positive for SARS-CoV-2 (RT-PCR or serology). Controls were patients pre-COVID-19 (n = 67) or within 24 hours of negative RT-PCR (n = 43).

Results: Specificities of N and S assays were 95-97% and 100%, respectively. In acute COVID-19 patients, N/S plasma assays …

Safety And Immunogenicity Of The Na-Apr-1 Hookworm Vaccine In Infection-Naïve Adults, David J Diemert, Maria Zumer, Doreen Campbell, Shannon Grahek, Guangzhao Li, Jin Peng, Maria Elena Bottazzi, Peter Hotez, Jeffrey Bethony

Center for Medical Ethics and Health Policy Staff Publications

Background: The Necator americanus hemoglobinase, aspartic protease-1 (Na-APR-1), facilitates the ability of adult hookworms to parasitize the intestine of their human hosts. A recombinant version of APR-1 protected laboratory animals against hookworm infection by inducing neutralizing antibodies that block the protein's enzymatic activity and thereby impair blood feeding. A catalytically inactive version of the wild-type hemoglobinase (Na-APR-1(M74)) was expressed by infiltrating Nicotiana benthamiana tobacco plants with an Agrobacterium tumefaciens strain engineered to express the vaccine antigen, which was adjuvanted with aluminum hydroxide adjuvant (Alhydrogel).

Methods: An open-label dose-escalation Phase 1 clinical trial was conducted in 40 healthy, hookworm-naïve adult volunteers …

Wellness Review 2022, Part 1, Martin Huecker, Brian A. Ferguson, Jacob Shreffler

Journal of Wellness

Introduction: This article represents the first of a two-part assessment of 2022 literature addressing wellness in healthcare professionals published from January 1, 2022 to June 30, 2022.

Methods: Three editors conducted a similar keyword search in Pubmed, also adding manually curated articles. Focusing chiefly on clinical trials and other prospective research, we settled on a final 25 significant papers focusing on wellness in medical professionals to include in this review.

Literature Review: Recent literature into HCW wellness continues to describe burnout factors and COVID-19 impact, but includes more resilience-targeting interventions and systematic reviews of trials seeking bolstering of well-being. Subsections …

On Conflict, Brenden Huynh

be Still

Conflict

In the past, I’ve always been one to avoid conflict. Conflict always had a negative connotation in my mind. I did whatever I could to avoid it. Because of my aversion to conflict, I have had to compromise my time and my efforts in numerous situations. I’ve held my tongue to prevent problems; but sometimes, this would lead to even more. This has affected me all my life, whether its a friend who said something I wasn’t fond of or a waitress that messed up my order, I almost never said anything simply to avoid conflict. Last year, I …

Towards A Definitive Symptom Structure Of Obsessive-Compulsive Disorder: A Factor And Network Analysis Of 87 Distinct Symptoms In 1366 Individuals, Matti Cervin, Euripedes C Miguel, Ayşegül Selcen Güler, Ygor A Ferrão, Ayşe Burcu Erdoğdu, Luisa Lazaro, Sebla Gökçe, Daniel A Geller, Yasemin Yulaf, Şaziye Senem Başgül, Özlem Özcan, Koray Karabekiroğlu, Leonardo F Fontenelle, Yankı Yazgan, Eric A Storch, James F Leckman, Maria Conceição Do Rosário, David Mataix-Cols

Center for Medical Ethics and Health Policy Staff Publications

Background: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques.

Methods: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the …

Incidence And 5-Year Survival Of Children And Adolescents With Hepatoblastoma In The United States, Justin A Kahla, David A Siegel, Shifan Dai, Philip J Lupo, Jennifer H Foster, Michael E Scheurer, Andras A Heczey

Center for Medical Ethics and Health Policy Staff Publications

Objective: Hepatoblastoma (HB) is the most common pediatric primary malignant liver tumor, its incidence has been increasing worldwide, but recent changes in incidence and outcomes with high population coverage are not well characterized.

Methods: We defined the incidence of HB diagnosed during 2003-2017 from United States Cancer Statistics (USCS) database, and survival during 2001-2016 from the National Program of Cancer Registries (NPCR). Data were stratified by sex, race/ethnicity, age, tumor stage, county population, and diagnosis year. Incidence trends were assessed by calculating average annual percent change (AAPC) using Joinpoint regression. Differences in overall 5-year survival were estimated using Cox regression …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …

Surveying The Stigma: How The Plhiv Stigma Index Acts As A Validated Framework To Measure Healthcare Discrimination And How It Can Be Adapted To Quantify Mental Health Stigma, Keeley Lariviere

Independent Study Project (ISP) Collection

The PLHIV Stigma Index is an ongoing, international study conducted by and for people living with HIV to measure the stigmatization that people living with HIV experience. As a model that has been proven successful in translating to targeted advocacy campaigns, this paper theorizes on how this Stigma Index could be broadened to capture other aspects of healthcare discrimination. With a growing demand for mental health support and a critically underdeveloped mental healthcare framework, understanding the stigma and discrimination that exist for people living with depression is a good place to start. Using mixed methods analysis from existing literature and …

Medical Ethics: How Resource Distribution Affects The Decision Making Of Doctors In Rural India: An Explorative And Comparative Study In Jamkhed, Maharashtra, Jared Yee

Independent Study Project (ISP) Collection

Using rural Mahrasthra as a case study, I was able to explore the medical ethics and common dilemmas that occur in Rural India. Through a collection of interviews and articles, I was able to piece together my understanding of some common ethical challenges that India faces, emphasizing ones that were unique to the location and circumstance. Using observations I made through my work in the hospital, I learned that limited resources effects all sides of ethics in the medical field, with a signficinant effect on economics, hospital structure, and clinical protocol. In an attempt to source the aspects of Indian …

Characteristics Of Graft-Versus-Host Disease (Gvhd) After Post-Transplantation Cyclophosphamide Versus Conventional Gvhd Prophylaxis, Rima M Saliba, Amin M Alousi, Joseph Pidala, Mukta Arora, Stephen R Spellman, Michael T Hemmer, Tao Wang, Camille Abboud, Sairah Ahmed, Joseph H Antin, Amer Beitinjaneh, David Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choe, Rabi Hanna, Peiman Hematti, Rammurti T Kamble, Carrie L Kitko, Mary Laughlin, Lazaros Lekakis, Margaret L Macmillan, Rodrigo Martino, Parinda A Mehta, Taiga Nishihori, Sagar S Patel, Miguel-Angel Perales, Hemalatha G Rangarajan, Olov Ringdén, Joseph Rosenthal, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Takanori Teshima, Marjolein Van Der Poel, Leo F Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A Yared, Jeffrey Schriber, Richard E Champlin, Stefan O Ciurea

Center for Medical Ethics and Health Policy Staff Publications

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin …

The Development And Initial Validation Of The Promis®+Hf-27 And Promis+Hf-10 Profiles, Faraz S Ahmad, Kathryn L Jackson, Susan E Yount, Nan E Rothrock, Michael A Kallen, Leilani Lacson, Karl Y Bilimoria, Abel N Kho, Raja Kannan Mutharasan, Peter A Mccullough, Jeffrey Bruckel, Savitri Fedson, Stephen E Kimmel, David T Eton, Kathleen L Grady, Clyde W Yancy, David Cella

Center for Medical Ethics and Health Policy Staff Publications

Aims: Heart failure (HF) is a common and morbid condition impacting multiple health domains. We previously reported the development of the PROMIS®-Plus-HF (PROMIS+HF) profile measure, including universal and HF-specific items. To facilitate use, we developed shorter, PROMIS+HF profiles intended for research and clinical use.

Methods and results: Candidate items were selected based on psychometric properties and symptom range coverage. HF clinicians (n = 43) rated item importance and clinical actionability. Based on these results, we developed the PROMIS+HF-27 and PROMIS+HF-10 profiles with summary scores (0-100) for overall, physical, mental, and social health. In a cross-sectional sample (n = 600), we …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …

T1 Signal Intensity Ratio Of The Pancreas As An Imaging Biomarker For The Staging Of Chronic Pancreatitis, Temel Tirkes, Anil K Dasyam, Zarine K Shah, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Stephanie T Chang, Carlos A Farinas, Joseph R Grajo, Kareem Mawad, Naoki Takahashi, Sudhakar K Venkatesh, Ashley Wachsman, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Stephen K Van Den Eeden, Yunlong Yang, Mark Topazian, Dana K Andersen, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.

Methods: The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their …

Residence In A Latinx Enclave And End-Induction Minimal Residual Disease Positivity Among Children With Acute Lymphoblastic Leukemia, Joshua P Muñiz, John P Woodhouse, Amy E Hughes, Sandi L Pruitt, Karen R Rabin, Michael E Scheurer, Philip J Lupo, Jeremy M Schraw

Center for Medical Ethics and Health Policy Staff Publications

Racial and ethnic inequities in survival persist for children with acute lymphoblastic leukemia (ALL). In the US, there are strong associations between SES, race/ethnicity, and place of residence. This is evidenced by ethnic enclaves: neighborhoods with high concentrations of ethnic residents, immigrants, and language isolation. The Latinx enclave index (LEI) can be used to investigate how residence in a Latinx enclave is associated with health outcomes. We studied the association between LEI score and minimal residual disease (MRD) in 142 pediatric ALL patients treated at Texas Children's Hospital. LEI score was associated with end-induction MRD positivity (OR per unit increase …

Longitudinal Investigation Of Suicidal Ideation And Associated Factors During Pediatric Acute Lymphoblastic Leukemia Chemotherapy, Kimberly P Raghubar, Tiffany Chambers, Ryan M Hill, Olga Taylor, Marilyn Hockenberry, M Casey Hooke, Pauline Mitby, Ida Ki Moore, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Objective: This study describes the prevalence of suicidal ideation (SI) during acute lymphoblastic leukemia (ALL) therapy and investigates the influence of clinical factors and physical symptoms on SI.

Methods: The Children's Depressive Inventory (CDI-2) was administered to ALL patients (diagnosed 2012-2017) at start of consolidation, delayed intensification (DI), maintenance cycle 1 (MC1), and maintenance cycle 2 (MC2) in a multi-site study. SI was present if patients endorsed the item "I want to kill myself." Logistic regression models evaluated associations between SI and sociodemographic factors; depressive symptoms; and below average, average, and above average symptom clusters identified using latent class analysis …

Considering The Genetic Architecture Of Hypoplastic Left Heart Syndrome, John W Belmont

Center for Medical Ethics and Health Policy Staff Publications

Hypoplastic left heart syndrome (HLHS) is among the most severe cardiovascular malformations and understanding its causes is crucial to making progress in prevention and treatment. Genetic analysis is a broadly useful tool for dissecting complex causal mechanisms and it is playing a significant role in HLHS research. However, unlike classical Mendelian disorders where a relatively small number of genes are largely determinative of the occurrence and severity of the disease, the picture in HLHS is complex. De novo single-gene and copy number variant (CNV) disorders make an important contribution, but there is emerging evidence for causal contributions from lower penetrance …