Health Policy Commons^™

A Phase 2 Trial Of Short-Term Intravenous N-Acetylcysteine In Biliary Atresia After Kasai Portoenterostomy, Sanjiv Harpavat, Kristin A Borovsky, Michael E Scheurer, Laurel Cavallo, Franca E Erhiawarie, Sanjeev Vasudevan, Adam M Vogel, Dana Cerminara, Elizabeth M Tessier, Kalyani R Patel, Sridevi Devaraj, Benjamin L Shneider

Center for Medical Ethics and Health Policy Staff Publications

Background: For infants with biliary atresia, the only treatment that can establish bile flow and delay need for liver transplant is the Kasai portoenterostomy (KP). Unfortunately, the KP has variable success. In this study, we hypothesized that intravenous N-acetylcysteine (IV NAC) treatment following KP would improve bile flow.

Methods: This was a phase 2 study following the two-stage "minimax" trial design. Participants received IV NAC (150 mg/kg/day) for 7 days after KP, and the primary endpoint was achieving total serum bile acids (TSBA) ≤10 μmol/L within 24 weeks of KP. Secondary endpoints were clinical markers and the occurrence of sentinel …

Against The Phrase "Aggressive Care", Trevor M Bibler

Center for Medical Ethics and Health Policy Staff Publications

Language is the primary technology clinical ethicists use as they offer guidance about norms. Like any other piece of technology, to use the technology well requires attention, intention, skill, and knowledge. Word choice becomes a matter of professional practice. The Brief Report offers clinical ethicists several reasons for rejecting the phrase "aggressive care." Instead, ethicists should consider replacing "aggressive care" with the adjacent concept of a "recovery-focused path." The virtues of this neologism include: the opportunity to set aside the emotion of "aggression," the phrase's accuracy when capturing the intention of the patient or their representative, and an unappreciated rhetorical …

Sequencing-Based Detection Of Measles In Wastewater: Texas, January 2025, Sara Javornik Cregeen, Michael J Tisza, Blake Hanson, Marissa Cook, Anil Surathu, Rebecca Schneider, Jingjing Wu, Kirstin Short, Kaavya Domakonda, Loren Hopkins, Matthew C Ross, Joseph F Petrosino, Jennifer Deegan, Lauren B Stadler, Eric Boerwinkle, Anthony Maresso

Center for Medical Ethics and Health Policy Staff Publications

Measles is a potentially deadly viral infection spread via respiratory droplets from infected individuals. Outbreaks occur when vaccine coverage drops below the threshold of herd, or community, immunity. Using a sequencing-based approach, we report the prospective (January 7, 2025) detection of measles in nucleic acid extracts from 2 wastewater treatment plants in Houston, Texas, with a population of more than 218 000 residents. The sequencing data from 2 samples contained 53 unique reads mapping to 11 different regions of the measles virus genome with a 99.4% match to genotype B3. Importantly, no detections were observed from 821 previous samples from …

"Holy Cow, Where Do I Sign Up?" Attitudes Of Military Veterans Toward Epigenomic Biomarker Toxic Exposure Testing, Stacey Pereira, Calvin Apodaca, Kyle Slominski, Rachele K Lipsky, Cristian Coarfa, Cheryl L Walker, Amy L Mcguire, Lea Steele, Drew A Helmer

Center for Medical Ethics and Health Policy Staff Publications

Introduction: After the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Promise to Address Comprehensive Toxics (PACT) Act in 2022, there has been a great interest in studying toxic exposures encountered during military service. Development of epigenomic biomarkers for exposures could facilitate understanding of exposure-related health effects, but such testing could also provide unwanted information.

Materials and methods: We explored attitudes toward epigenomic biomarker research and the potential to test for past exposures using semistructured interviews with Veterans (n = 22) who experienced potentially harmful exposures.

Results: Twenty Veterans said they would hypothetically want to receive …

Senior Health (Age 65+) In The Mountain West, 2024, Taylor Volk, Kristian Thymianos, Caitlin J. Saladino, William E. Brown Jr.

Health

This fact sheet presents senior health care statistics for the Mountain West states of Arizona, Colorado, Nevada, New Mexico, and Utah. The “2024 Senior Report – State Summaries,” study from America’s Health Rankings, United Foundation provided the data for all fifty states and Washington, D.C.

Multiscale Modeling Of Drug-Induced Liver Injury From Organ To Lobule, Alon Malka-Markovitz, Stelian Camara Dit Pinto, Mohammed Cherkaoui, Steven M Levine, Sharmila Anandasabapathy, Gagan K Sood, Sadhna Dhingra, Gao Yujia, John M Vierling, Nicolas R Gallo

Center for Medical Ethics and Health Policy Staff Publications

Drug-induced liver injury poses significant challenges in drug development and in clinical care. This study builds on prior work developing a Human Liver Virtual Twin by creating a Multiscale Computational Fluid Dynamics framework that integrates patient-specific anatomical data to predict acetaminophen-induced liver injury as a demonstration of its capability. The model bridges vascular, lobular, and cellular scales to simulate dynamic blood flow, drug transport, and injury mechanisms that accurately reflect clinically observed spatial heterogeneity. Results demonstrate accurate blood flow dynamics, predictions of hepatocellular damage, and a scalable framework for studying spatial heterogeneity applicable to other hepatic pathologies. This work establishes …

The Case For Compulsory Dna Testing At Birth To Confirm Paternity: Ethical, Legal, And Social Considerations, Michael Mncedisi Willie

Journal of Indonesian Health Policy and Administration

Compulsory paternity testing at birth has sparked significant legal, ethical, and social debate due to its potential impact on family dynamics, child well-being, and parental responsibility. This review explores the ethical, legal, and societal implications of such testing, using Bioecological Systems Theory and Rawls' Theory of Justice to frame the discussion. This review evaluates the benefits and challenges of mandatory DNA testing at birth, particularly in reducing paternity fraud, ensuring fairness in child support allocation, and enhancing socio-economic outcomes, especially in low-income households. This qualitative review draws on multidisciplinary literature from family law, genetic counseling, social policy, and fathers' rights …

The Social Standing Versus The Mind Standing Of Older Adults In Egypt: Cross-Sectional Analysis Of The Relationship Between Social Capital And Cognitive Functions, Shaza H. Shinaishen Dr

Theses and Dissertations

Introduction: Egypt's population, much like that of other countries, is expected to age considerably over the course of the coming decades. Although biological and socioeconomic predictors of cognitive function have been studied widely, personal level social capital remains unexplored, especially in LMICs.

Purpose: This study primarily investigates the relationship between individual social capital and cognitive functioning among older adults aged 65 years and older in Egypt using the structural and cognitive components of social capital, including group membership, civic engagements, and caregiving roles.

Methods: A cross-sectional survey on 363 older individuals in different geographical and demographic segments of Egypt using …

Survival Guide For Queer Families In Heteronormative Healthcare: Liberatory Consciousness And The Paradox Of Dependent Healthcare, A Critical Policy Discourse Analysis, Dwenna A. Holden

Electronic Theses and Dissertations

In this study I explored and analyzed how the queer experiences of an anonymous higher education institution in the western United States’ self-identified queer faculty and staff intersected with the discursive framing of the college’s dependent healthcare structure and documents. Within a critical paradigm I designed research around a high-density theoretical approach to weaving various branches of queer theory together with critical theory around policy and law in relation to queer bodies and hostile heteronormative policy environments. I arrived at solutions based in complaint, survival, and transformation. I used critical policy discourse analyses to interrogate the college’s dependent healthcare documents …

Comparative Effects Of Combustible Cigarette Versus Electronic Cigarette Exposures On Kras Mutant Lung Cancer Promotion, Walter V Velasco, Maria T Grimaldo, Nastaran Karimi, Michael J Clowers, Avantika Krishna, Ranran Wu, Rahmah Ejaz, Bo Yuan, Segundo Del Aguila, Iman Bouchelkia, Javier Eduardo Moreno Barragan, Katherine E Larsen, Yasmina Rezai, Farbod Khalaj, Kyler Mitra, Carlos Reyna Rodriguez, Ricardo Millares, Angelica Baca De Anda, Susana Castro-Pando, Umesh C Karandikar, Joseph F Petrosino, Florencia Mcallister, Humam Kadara, Edwin J Ostrin, Johannes F Fahrmann, Kristi Louise Hoffman, Seyed Javad Moghaddam

Center for Medical Ethics and Health Policy Staff Publications

Despite the emerging public health concern related to the use of electronic cigarette vapors (ECV), its impact on lung cancer is poorly understood. We assessed the effect of ECV on lung tumorigenesis in a mouse model of lung adenocarcinoma. Mice were exposed to either room air, combustible cigarette smoke (CCS), or ECV 2 hours daily for 8 weeks at which lung samples were harvested and studied for different outcomes. We found that CCS, but not ECV, led to a significant increase in tumor burden. Immunophenotyping of both CCS- and ECV-exposed lungs displayed pronounced pro-tumor immunosuppressive phenotypes, characterized by significantly decreased …

Attitudes Toward Pig Islet Xenotransplantation For Type 1 Diabetes: A Scoping Review, Daniel J Hurst, Daniel Rodger, Luz A Padilla, Fernando Ovalle

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Over 8 million people globally have type 1 diabetes. Islet allotransplantation offers an alternative to insulin therapy but is constrained by donor availability. Genetically modified pig islet transplantation presents a potential solution, yet understanding stakeholder attitudes is crucial before clinical adoption.

METHODS: This scoping review followed Joanna Briggs Institute methodology and PRISMA guidelines. CINAHL, EMBASE, PubMed, PsychINFO, and SCOPUS were searched for studies examining attitudes toward pig islet xenotransplantation among patients, healthcare workers, and other stakeholders.

RESULTS: From 199 sources, 16 met eligibility criteria, spanning ten countries from 2003 to 2023. The 23,780 participants included 1,535 (6.5%) patients/family members, …

Self-Collection For Cervical Cancer Screening In A Safety-Net Setting: The Prestis Randomized Clinical Trial, Jane R Montealegre, Susan G Hilsenbeck, Shaun Bulsara, Susan L Parker, Trisha L Amboree, Matthew L Anderson, Maria Daheri, Maria L Jibaja-Weiss, Kathleen M Schmeler, Ashish A Deshmukh, Elizabeth Y Chiao, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Importance: There are limited data on the effectiveness of mailed self-collection to increase cervical cancer screening (CCS) participation in underresourced health care settings.

Objective: To compare the effectiveness of mailed self-collection kits, with and without patient navigation, to telephone reminders to increase CCS in a safety-net health system.

Design, setting, and participants: This pragmatic, parallel, single-blinded, randomized clinical trial within a publicly funded safety-net health system in Houston, Texas, compared (1) telephone reminder (TR) for clinic-based screening, (2) TR with mailed self-collection (SC), and (3) TR with mailed SC and patient navigation among a random sample of CCS-eligible patients not …

Prediction Of Methotrexate Neurotoxicity Using Clinical, Sociodemographic, And Area-Based Information In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, Maria Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown

Center for Medical Ethics and Health Policy Staff Publications

Background: Methotrexate is a critical component of pediatric acute lymphoblastic leukemia (ALL) therapy that can result in neurotoxicity which has been associated with an increased risk of relapse. We leveraged machine learning to develop a neurotoxicity risk prediction model in a diverse cohort of children with ALL.

Methods: We included children (age 2-20 years) diagnosed with ALL (2005-2019) and treated in Texas without pre-existing neurologic disease. Clinical information was obtained by medical record review. Neurotoxicity occurring post-induction and prior to maintenance therapy was defined as neurologic episodes occurring within 21 days of methotrexate. Suspected cases were independently confirmed by 2 …

The Effect Of Ex-Ante Government Responsibility For Health On Public Health Financing In Post Pandemic Budgets, Denis Granados, Rylee Roman, Hallie Sidman

Working Papers Series

This paper investigates how pre-pandemic levels of government responsibility for public health financing influenced post-pandemic health spending across selected OECD countries. Using a combination of descriptive analysis and regression modeling, the study examines changes in public health expenditure per capita between 2019 and 2022, focusing on key variables such as the government’s share of health financing, the Total Pandemic Policy Intensity (PPI) index, and GDP per capita. Findings suggest that while all countries increased health spending post-COVID-19, the scale of change varied significantly based on economic capacity, institutional readiness, and political will. Notably, countries with higher pre-pandemic public health investment …

Functional Resilience Of Healthcare In The Critical Juncture Of The Covid-19 Pandemic, Avner Kronisch, Christian Bongiorno, Kerane Smith, John Baker

Working Papers Series

This paper offers a comparative analysis of eight national healthcare systems—spanning democracies, autocracies, and various institutional models—to evaluate resilience during the COVID-19 pandemic. Drawing on Shvetsova et al.’s framework of informational and authority redundancies, and Parker & Klein’s “choke point” theory of healthcare rationing, we examine how institutional structure shaped pandemic response, system adaptability, and continuity of non-COVID services. Using indicators like life expectancy, under-five mortality, hospital capacity, cancer survival, and excess mortality, we explore how systems absorbed shock and maintained essential care. We find that decentralized and polycentric governance structures, when paired with coordination and resource adequacy, enhanced resilience—exemplified …

Covid-19 & Healthcare (Re)Privatization? A Comparative Analysis Of High And Medium Per Capita Gdp Countries, Kristina Donders, Kaitlyn Matthews, Brittany Reyes, Frank. H. Rizzo

Working Papers Series

This paper examines whether the COVID-19 pandemic accelerated healthcare privatization in high- and medium-GDP countries. Drawing on political economy theories of path dependence and privatization, we analyze changes in public and private healthcare expenditures in eight countries: Canada, Chile, Denmark, Georgia, Luxembourg, Norway, the Philippines, and South Korea—comparing data from 2019 and 2022. Using World Bank indicators on healthcare financing, GDP, aging populations, and food insecurity, we find that although healthcare expenditures generally increased during the pandemic, this increase was primarily in public, not private, spending. Case studies of Georgia and South Korea reveal that local economic and demographic pressures, …

Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Center for Medical Ethics and Health Policy Staff Publications

Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.

Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …

Maternal Loss Of Mouse Nlrp2 Alters The Transcriptome And Dna Methylome In Gv Oocytes And Impairs Zygotic Genome Activation In Embryos, Zahra Anvar, Michael D Jochum, Imen Chakchouk, Momal Sharif, Hannah Demond, Alvin K To, Daniel C Kraushaar, Ying-Wooi Wan, Michael C Mari, Simon Andrews, Gavin Kelsey, Ignatia B Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Background: NLRP2 is a subcortical maternal complex (SCMC) protein of mammalian oocytes and preimplantation embryos. SCMC proteins are encoded by maternal effect genes and play a pivotal role in the maternal-to-zygotic transition (MZT), early embryogenesis, and epigenetic (re)programming. Maternal inactivation of genes encoding SCMC proteins has been linked to infertility and subfertility in mice and humans, but the underlying molecular mechanisms for the diverse functions of SCMC proteins, and specifically the role of NLRP2, are incompletely understood.

Results: We profiled the DNA methylome of pre-ovulatory germinal-vesicle (GV) oocytes from Nlrp2-null, heterozygous (Het), and wild-type (WT) female mice and assessed the …

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …

How Far-Right Populism Harms Ethnic Minorities’ Health: The Case Of The United States, Dina Rosenberg

Working Papers Series

Public health is a political issue, and the health of ethnic minorities is a key component of it. We argue that far-right populism, whether grassroots or elitist, harms the health of immigrants and minorities. Anti-minority attitudes and policies—such as health chauvinism promoted by far-right populists—along with hate rhetoric and ensuing personal and institutional discrimination create a climate of hostility that negatively affects health outcomes in underprivileged communities. We hypothesize that immigrants and ethnic minorities living in such a climate are more likely to experience health problems and underutilize healthcare. To test this, we leverage the significant variation between U.S. states …

Ocular Phenotyping Of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes, Abraham Hang, Andy Shao, Michael Shea, Michel J Roux, Denise M Imai-Leonard, David J Adams, Takanori Amano, Oana V Amarie, Zorana Berberovic, Raphaël Bour, Lynette Bower, Brian C Leonard, Steve D Brown, Soo Young Cho, Sharon Clementson-Mobbs, Abigail J D'Souza, Mary Dickinson, Mohammad Eskandarian, Ann M Flenniken, Helmut Fuchs, Valerie Gailus-Durner, Jason Heaney, Yann Hérault, Martin Hrabe De Angelis, Chih-Wei Hsu, Shundan Jin, Russell Joynson, Yeon Kyung Kang, Haerim Kim, Hiroshi Masuya, Ki-Hoan Nam, Hyuna Noh, Lauryl M J Nutter, Marcela Palkova, Jan Prochazka, Miles Joseph Raishbrook, Fabrice Riet, Jason Salazar, John Richard Seavitt, Radislav Sedlacek, Mohammed Selloum, Kyoung Yul Seo, Je Kyung Seong, Hae-Sol Shin, Toshihiko Shiroishi, Tania Sorg, Michelle Stewart, Masaru Tamura, Heather Tolentino, Uchechukwu Udensi, Sara Wells, Wolfgang Wurst, Atsushi Yoshiki, Hamid Meziane, Glenn Yiu, Paul A Sieving, Louise Lanoue, K C Kent Lloyd, Colin Mckerlie, Ala Moshiri, International Mouse Phenotyping Consortium (Impc)

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.

Methods: The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), …

An Assessment Of Maine's Capacity To Support Transitions Of Care Through The Substance Use Disorder Continuum, Mary Lindsey Smith Phd, Sarah Mclaughlin Mph, Rachel M. Gallo Mph

Substance Use Research & Evaluation

This report evaluates Maine's capacity to support effective transitions of care across the substance use disorder (SUD) treatment continuum. Using data collected from a statewide survey of 65 SUD providers, conducted from February to April 2025, the study examines organizational practices, inter-provider communication, and coordination strategies related to transitions between levels of care: medically supervised withdrawal, inpatient, and outpatient treatment programs. Key findings reveal strong intra-organizational communication, widespread understanding of ASAM criteria, and a general commitment to patient-centered care. However, gaps persist in coordination between care levels, particularly in withdrawal management programs, which rarely conduct follow-ups or collaborate with outpatient …

Withdrawal Management In Maine: Capacity Challenges And Opportunities For Improvement, Mary Lindsey Smith Phd, Katie Rosingana Ba, Tyler Egeland Ba, Sarah Mclaughlin Mph

Substance Use Research & Evaluation

This summary report presents findings from healthcare provider interviews conducted in 2024 to assess the current landscape of withdrawal management (WM) services in Maine. Sixteen providers, across eight counties and representing a range of substance use disorder (SUD) service types, were interviewed to evaluate capacity, challenges, and opportunities for improvement across the continuum of care. Thematic analysis identified widespread gaps in withdrawal management capacity, especially in ASAM Levels 1.7 to 4.0, with critical shortages in ambulatory and low-intensity residential services. Key barriers included geographic inequities, insufficient infrastructure, long waitlists, inadequate reimbursement, and workforce shortages exacerbated by stigma and provider discomfort. …

Feedback On Withdrawal Management Services In Maine From Persons With Lived Experience, Mary Lindsey Smith Phd, Katie Rosingana Ba

Substance Use Research & Evaluation

This summary report presents findings from interviews with twelve persons with lived experience of substance use disorder (PWLE). The interviews asked persons in recovery about their experiences accessing withdrawal management and broader substance use treatment services across Maine. Participants identified key barriers to treatment including high costs, limited bed availability, long wait times, geographic inaccessibility, and lack of centralized information. Gaps in service infrastructure, particularly for opioid withdrawal management, long-term treatment, and transition supports post-detox, were widely reported. Participants emphasized the critical need for more localized and individualized services, particularly for parents, rural residents, and low-income individuals. Recommendations include expanding …

Path Dependency And The Politics Of U.S. Health Reform, Sophia Spadafore

Dissertations, Theses, and Capstone Projects

This study examines the impact of path dependency on health reform efforts in the United States, specifically analyzing how past policy decisions constrain subsequent reform possibilities. Utilizing the theoretical framework of historical institutionalism, the study investigates two significant cases—the passage of Medicare and Medicaid in 1965 and the The Patient Protection and Affordable Care Act (ACA) in 2010—to illustrate how successful healthcare reforms embed institutional arrangements that limit future policy innovation. Through a comparative case study approach grounded in legislative records, historical texts, and scholarly analyses, the research highlights that major healthcare reforms in the U.S. have consistently been structured …

A Meta-Analysis Of Diagnostic Yield And Clinical Utility Of Genome And Exome Sequencing In Pediatric Rare And Undiagnosed Genetic Diseases, Rajshree Pandey, Noemi Fluetsch Brennan, Kalliopi Trachana, Sarah Katsandres, Olaf Bodamer, John Belmont, David L Veenstra, Siyang Peng

Center for Medical Ethics and Health Policy Staff Publications

Purpose: To systematically evaluate the diagnostic yield and clinical utility of genome sequencing (GS) and exome sequencing (ES; genome-wide sequencing [GWS]) in pediatric patients with rare and undiagnosed genetic diseases.

Methods: We conducted a meta-analysis of studies published between 2011 and 2023. To address study heterogeneity, comparative analyses included within-cohort studies using random-effects models.

Results: We identified 108 studies including 24,631 probands with diverse clinical indications. The pooled diagnostic yield among within-cohort studies (N = 13) for GWS was 34.2% (95% CI: 27.6-41.5; I2: 86%) vs 18.1% (95% CI: 13.1-24.6; I2: 89%) for non-GWS, with 2.4-times odds of diagnosis (95% …

International Society For Cell & Gene Therapy Expanded Access Working Group Position Paper: Key Considerations To Support Equitable And Ethical Expanded Access To Investigational Cell- And Gene-Based Interventions, Elena Maryamchik, Laertis Ikonomou, Beth E Roxland, Felix Grignon, Bruce L Levine, Bambi J Grilley

Center for Medical Ethics and Health Policy Staff Publications

This position paper reviews the Expanded Access pathway for cell and gene therapies, examining its critical role at the nexus of patient need, regulatory frameworks, and scientific advancement. Spearheaded by the International Society for Cell & Gene Therapy's Expanded Access Working Group, it explores how investigational therapies are accessed outside of clinical trials for patients with serious or life-threatening conditions when no approved alternatives exist. Access to cell and gene therapy products are of specific interest to patients because many times the products are bespoke, being used to treat serious and/or incurable conditions, and are potentially curative. As the field …

Joint Analysis Of The Npod-Virus Group Data: The Association Of Enterovirus With Type 1 Diabetes Is Supported By Multiple Markers Of Infection In Pancreas Tissue, Sarah J Richardson, Teresa Rodriguez-Calvo, Jutta E Laiho, John S Kaddis, Julius O Nyalwidhe, Irina Kusmartseva, Sofia Morfopoulou, Joseph F Petrosino, Vincent Plagnol, Kathrin Maedler, Margaret A Morris, Jerry L Nadler, Mark A Atkinson, Matthias Von Herrath, Richard E Lloyd, Heikki Hyoty, Noel G Morgan, Alberto Pugliese, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: Previous pathology studies have associated enterovirus infections with type 1 diabetes by examining the enterovirus capsid protein 1 (VP1) in autopsy pancreases obtained near diabetes diagnosis. The Network for Pancreatic Organ Donors with Diabetes (nPOD) has since obtained pancreases from organ donors with type 1 diabetes (with broad age and disease duration) and donors with disease-associated autoantibodies (AAbs), the latter representing preclinical disease. Two accompanying manuscripts from the nPOD-Virus Group report primary data from a coordinated analysis of multiple enterovirus indices. We aimed to comprehensively assess the association of multiple enterovirus markers with type 1 diabetes.

Methods: The nPOD-Virus …

Detection Of Enterovirus Rna In Pancreas And Lymphoid Tissues Of Organ Donors With Type 1 Diabetes, Jutta E Laiho, Sami Oikarinen, Sofia Morfopoulou, Maarit Oikarinen, Ashlie Renner, Daniel Depledge, Matthew C Ross, Ivan C Gerling, Judith Breuer, Joseph F Petrosino, Vincent Plagnol, Alberto Pugliese, Antonio Toniolo, Richard E Lloyd, Heikki Hyöty, Npod-Virus Group

Center for Medical Ethics and Health Policy Staff Publications

Aims/hypothesis: The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. The aim of the current work was to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and without type 1 diabetes.

Methods: We analysed pancreas, spleen, pancreatic lymph nodes and duodenum samples from the following groups: (1) donors with type 1 diabetes (n=71) with (n=35) or without (n=36) insulin-containing islets; (2) donors with single or …

A Multi-Site Study Of Clinician Perspectives In The Lifecycle Of An Algorithmic Risk Prediction Tool, Rita Dexter, Kristin Kostick-Quenet, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Recent advancements in the performative capacities of artificial intelligence (AI), machine learning (ML), and algorithmic-based tools open up numerous applications in modern medicine. There are, however, few studies that track the whole lifecycle of a digital healthcare tool as it evolves from conception, to design, and deployment in real world settings-especially with a focus on the social dynamics amongst the end-users of the tool: clinicians. In this paper, we present data from a multi-site, 5-year study focused on the development and deployment of an algorithmic risk calculator (HeartMate 3 Risk Score) into a validated and efficacy tested clinical decision support …