Bioethics and Medical Ethics Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Covid-19 And Children, Carl A Pierce, Kevan C Herold, Betsy C Herold, Janet Chou, Adrienne Randolph, Binita Kane, Sammie Mcfarland, Deepti Gurdasani, Christina Pagel, Peter Hotez, Sarah Cobey, Scott E Hensley

Center for Medical Ethics and Health Policy Staff Publications

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in …

Targeting Glycans For Car Therapy: The Advent Of Sweet Cars, Zoe Raglow, Mary Kathryn Mckenna, Challice L Bonifant, Wenjing Wang, Marina Pasca Di Magliano, Johannes Stadlmann, Josef M Penninger, Richard D Cummings, Malcolm K Brenner, David M Markovitz

Center for Medical Ethics and Health Policy Staff Publications

Chimeric antigen receptor (CAR) T cell therapy has created a paradigm shift in the treatment of hematologic malignancies but has not been as effective toward solid tumors. For such tumors, the primary obstacles facing CAR T cells are scarcity of tumor-specific antigens and the hostile and complex tumor microenvironment. Glycosylation, the process by which sugars are post-translationally added to proteins or lipids, is profoundly dysregulated in cancer. Abnormally glycosylated glycoproteins expressed on cancer cells offer unique targets for CAR T therapy as they are specific to tumor cells. Tumor stromal cells also express abnormal glycoproteins and thus also have the …

Can Statins Lessen The Burden Of Virus Mediated Cancers?, Eva H Clark, Sarah T Ahmed, Elaine Chang, Elizabeth Y Chiao, Donna L White

Center for Medical Ethics and Health Policy Staff Publications

Background: Oncogenic viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), Epstein Barr virus (EBV), and Kaposi Sarcoma Herpes virus (KSHV) contribute to a significant proportion of the world's cancers. Given the sizeable burden of virus mediated cancers, development of strategies to prevent and/or treat these cancers is critical. While large population studies suggest that treatment with hydroxymethylglutaryl-CoA reductase inhibitors, commonly known as statins, may reduce the risk of many cancer types including HBV/HCV related hepatocellular carcinoma, few studies have specifically evaluated the impact of statin use in populations at risk for other types of virus …

Leveraging Clinical Trial Populations And Data From The Children's Oncology Group For Cancer Survivorship Research, Eric J Chow, Lena E Winestone, Philip J Lupo, Lisa R Diller, Tara O Henderson, Nina S Kadan-Lottick, Jennifer M Levine, Kirsten K Ness, Smita Bhatia, Saro H Armenian

Center for Medical Ethics and Health Policy Staff Publications

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship …

High Prevalence Of Osteopathy In Chronic Pancreatitis: A Cross-Sectional Analysis From The Proceed Study, Phil A Hart, Dhiraj Yadav, Liang Li, Savi Appana, William Fisher, Evan Fogel, Chris E Forsmark, Walter G Park, Stephen Pandol, Mark D Topazian, Stephen K Van Den Eden, Santhi Swaroop Vege, David Bradley, Jose Serrano, Darwin L Conwell

Center for Medical Ethics and Health Policy Staff Publications

Background & aims: Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.

Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression …

Vaccine-Linked Chemotherapy With A Low Dose Of Benznidazole Plus A Bivalent Recombinant Protein Vaccine Prevents The Development Of Cardiac Fibrosis Caused By Trypanosoma Cruzi In Chronically-Infected Balb/C Mice, Victor Manuel Dzul-Huchim, Maria Jesus Ramirez-Sierra, Pedro Pablo Martinez-Vega, Miguel Enrique Rosado-Vallado, Victor Ermilo Arana-Argaez, Jaime Ortega-Lopez, Fabian Gusovsky, Eric Dumonteil, Julio Vladimir Cruz-Chan, Peter Hotez, María Elena Bottazzi, Liliana Estefania Villanueva-Lizama

Center for Medical Ethics and Health Policy Staff Publications

Background: Chagas disease (CD) is caused by Trypanosoma cruzi and affects 6-7 million people worldwide. Approximately 30% of chronic patients develop chronic chagasic cardiomyopathy (CCC) after decades. Benznidazole (BNZ), one of the first-line chemotherapy used for CD, induces toxicity and fails to halt the progression of CCC in chronic patients. The recombinant parasite-derived antigens, including Tc24, Tc24-C4, TSA-1, and TSA-1-C4 with Toll-like receptor 4 (TLR-4) agonist-adjuvants reduce cardiac parasite burdens, heart inflammation, and fibrosis, leading us to envision their use as immunotherapy together with BNZ. Given genetic immunization (DNA vaccines) encoding Tc24 and TSA-1 induce protective immunity in mice and …

Change During Cognitive And Exposure Phases Of Cognitive-Behavioral Therapy For Autistic Youth With Anxiety Disorders, Andrew G Guzick, Sophie C Schneider, Philip C Kendall, Jeffrey J Wood, Connor M Kerns, Brent J Small, Ye Eun Park, Sandra L Cepeda, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Objective: To evaluate improvement during the (a) cognitive and (b) exposure therapy phases of cognitive-behavioral therapy (CBT) for autistic youth with anxiety disorders.

Method: Participants were 148 autistic youth (aged 7-13; 77% male; 64% White) with clinically significant anxiety who were randomized to standard or adapted CBT. Clinician-rated anxiety severity was recorded at each appointment. Trajectories of change during (a) the cognitive phase and (b) the exposure phase of treatment were analyzed using piecewise multilevel modeling.

Results: Compared to the psychoeducation and cognitive therapy phases, the exposure phase corresponded with significantly more rapid symptom reduction, b = -.11, 95% CI …

Recommendations For Whole Genome Sequencing In Diagnostics For Rare Diseases, Erika Souche, Sergi Beltran, Erwin Brosens, John W Belmont, Magdalena Fossum, Olaf Riess, Christian Gilissen, Amin Ardeshirdavani, Gunnar Houge, Marielle Van Gijn, Jill Clayton-Smith, Matthis Synofzik, Nicole De Leeuw, Zandra C Deans, Yasemin Dincer, Sebastian H Eck, Saskia Van Der Crabben, Meena Balasubramanian, Holm Graessner, Marc Sturm, Helen Firth, Alessandra Ferlini, Rima Nabbout, Elfride De Baere, Thomas Liehr, Milan Macek, Gert Matthijs, Hans Scheffer, Peter Bauer, Helger G Yntema, Marjan M Weiss

Center for Medical Ethics and Health Policy Staff Publications

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions. The use of WGS in diagnostics warrants the re-evaluation …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

Faculty, Staff and Student Publications

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …