Bioethics and Medical Ethics Commons^™

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 …

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 …

Will Anti-Vaccine Activism In The Usa Reverse Global Goals?, Peter J Hotez

Center for Medical Ethics and Health Policy Staff Publications

In the time of the COVID-19 pandemic, anti-vaccine activism in the USA accelerated, amplified and formed an alliance with political groups and even extremists. An organized, well-funded and empowered anti-science movement now threatens to spill over and threaten all childhood immunizations in the USA and globally.

An Ultra-Brief Screening Scale For Pediatric Obsessive-Compulsive Disorder: The Oci-Cv-5, Amitai Abramovitch, Jonathan S Abramowitz, Dean Mckay, Heining Cham, Kennedy S Anderson, Lara J Farrell, Daniel A Geller, Gregory L Hanna, Sharna Mathieu, Joseph F Mcguire, David R Rosenberg, S Evelyn Stewart, Eric A Storch, Sabine Wilhelm

Center for Medical Ethics and Health Policy Staff Publications

Background: Obsessive-compulsive disorder (OCD) is an often disabling and chronic condition that is normally assessed using diagnostic interviews or lengthy self-report questionnaires. This makes routine screening in general health settings impractical, and as a result OCD is often under-(or mis-)recognized. The present study reports on the development of an ultra-brief version of the Obsessive-Compulsive Inventory-Child Version (OCI-CV) which may be administered routinely as a screener for pediatric OCD.

Method: A total of 489 youth diagnosed with OCD, 259 non-clinical controls, and 299 youth with other disorders completed the OCI-CV and other indices of psychopathology. Using item analyses, we extracted five …

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 …

Rates Of Laboratory Adverse Events By Course In Paediatric Leukaemia Ascertained With Automated Electronic Health Record Extraction: A Retrospective Cohort Study From The Children’S Oncology Group, Tamara P Miller, Kelly D Getz, Yimei Li, Biniyam G Demissei, Peter C Adamson, Todd A Alonzo, Evanette Burrows, Lusha Cao, Sharon M Castellino, Marla H Daves, Brian T Fisher, Robert Gerbing, Robert W Grundmeier, Edward M Krause, Judy Lee, Philip J Lupo, Karen R Rabin, Mark Ramos, Michael E Scheurer, Jennifer J Wilkes, Lena E Winestone, Douglas S Hawkins, M Monica Gramatges, Richard Aplenc

Center for Medical Ethics and Health Policy Staff Publications

Background: Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia.

Methods: For this retrospective cohort study from the Children's Oncology Group (COG), we included patients aged 0-22 years treated for acute myeloid leukaemia or acute lymphoblastic leukaemia at Children's Healthcare of Atlanta (Atlanta, GA, USA) from Jan 1, 2010, to Nov 1, 2018, at the Children's Hospital of Philadelphia …

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 …

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 …

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 …

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 …

Years Of Life Lost Associated With Covid-19 Deaths In The Usa During The First 2 Years Of The Pandemic, Troy Quast, Ross Andel, Sean Gregory, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Prior estimates of the years of life lost (YLLs) in the USA associated with coronavirus disease 2019 (COVID-19) were 1.2 million through 11 July 2020 and 3.9 million through 31 January 2021 (which roughly coincides with the first full year of the pandemic). The aim of this study is to update YLL estimates through the first 2 years of the pandemic.

Methods: We employed data regarding COVID-19 deaths through 5 February 2022 by jurisdiction, gender and age group. We used actuarial life expectancy tables by gender and age to estimate YLLs.

Results: We estimated roughly 9.7 million YLLs due …

Ethical Oversight Of Roles & Relationships In Treatment & Research In Advanced Disease States, Alexa Vercelli

Electronic Theses and Dissertations

There is often ethical analysis focusing solely on the care of the patient by the physician or on the protection of the research participant by the clinical investigator, but those two are often overlapping. By paralleling the analysis of treatment and research, it emphasizes the specific ethical approaches necessary for individuals facing advanced diseases states in the separate roles of being a patient or participant. It also gives guidance to the complexity of the ethics surrounding medical professionals who float between the roles of treating physicians and clinical investigators. As individuals with advanced disease states are considered a vulnerable population …

Respecting The Ethical Tension Between Surveillance And Privacy In Promoting Public Health And Disease Management, Kamal Althobaiti

Electronic Theses and Dissertations

The recognition of the need to undertake surveillance and to protect privacy is well established. However, the continually changing circumstances and fast-paced development of healthcare today requires a continuing need to respect this ethical tension between surveillance and privacy. Hence, this dissertation is to respect the ethical tension between surveillance and privacy in promoting public health and disease management. This dissertation investigates the ethics of conducting public health surveillance, including the challenges associated with obtaining consent and protecting data from unauthorized access. The dissertation will focus on the ethical consequences of big data, including issues associated with obtaining informed consent, …

Random Field Modeling Of Multi-Trait Multi-Locus Association For Detecting Methylation Quantitative Trait Loci, Chen Lyu, Manyan Huang, Nianjun Liu, Zhongxue Chen, Philip J Lupo, Benjamin Tycko, John S Witte, Charlotte A Hobbs, Ming Li

Center for Medical Ethics and Health Policy Staff Publications

Motivation: CpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another.

Results: We propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between a set of CpG sites and a set of genetic variants. The proposed method has several advantages. First, it is a multi-trait method that allows flexible correlation structures between neighboring CpG sites (e.g. distance-based correlation). Second, it is also a multi-locus method that integrates the effect of multiple common and rare genetic variants. Third, it models …

Safety And Tolerability Of Carboplatin And Paclitaxel In Cancer Patients With Hiv (Amc-078), An Aids Malignancy Consortium (Amc) Study, Missak Haigentz, Page Moore, Milan Bimali, Timothy Cooley, Joseph Sparano, Michelle Rudek, Lee Ratner, David Henry, Juan Ramos, John Deeken, Paul Rubinstein, Elizabeth Chiao

Center for Medical Ethics and Health Policy Staff Publications

Background: Persons living with human immunodeficiency virus are an underserved population for evidence-based cancer treatment. Paclitaxel and carboplatin (PCb) is an active regimen against a variety of solid tumors, including several seen in excess in patients with HIV infection. We performed a pilot trial to evaluate the safety of full-dose PCb in people living with human immunodeficiency virus and cancer.

Methods: Eligible patients, stratified by concurrent antiretroviral therapy (ART) that included CYP3A4 inhibitors or not, received paclitaxel (175 mg/m2) in combination with carboplatin (target AUC 6) intravenously every 3 weeks for up to 6 cycles.

Results: Sixteen evaluable patients received …

Prevalence Of Human Papillomavirus Infection Among Women Born In The 1990s Vs The 1980s And Association With Hpv Vaccination In The Us, Zahed Shahmoradi, Haluk Damgacioglu, Jane Montealegre, Elizabeth Y Chiao, Keith Sigel, Kalyani Sonawane, Ashish A Deshmukh

Center for Medical Ethics and Health Policy Staff Publications

This cross-sectional study examines rates of human papillomavirus infections among a cohort of vaccinated and unvaccinated women born in the 1990s.

Ethical Considerations Of Telehealth: Access, Inequity, Trust, And Overuse, Monica O'Reilly-Jacob, Andrea Vicini, Ashley P. Duggan

Journal of Health Ethics

In the U.S. healthcare system, telehealth is increasingly present and demands ethical assessment. On the one hand, telehealth increases access to healthcare services for some at-risk populations (e.g., people suffering from mental illness and addictions) and in specific contexts (e.g., rural). On the other hand, telehealth widens the digital divide and can lead to overuse of services. Furthermore, because it is still unclear how telehealth influences trust between patients and primary care clinicians, connecting relationship science and human communication research can inform critical reasoning. Finally, healthcare policy is advancing toward the wide adoption of telehealth. Hence, it is urgent to …