Health Policy Commons^™

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

Center for Medical Ethics and Health Policy Staff Publications

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

How Have Researchers Defined Institutions, Politics, Organizations And Governance In Research Related To Epidemic And Pandemic Response? A Scoping Review To Map Current Concepts, Laura Jane Brubacher

Faculty, Staff and Student Publications

In recent years, the literature on public health interventions and health outcomes in the context of epidemic and pandemic response has grown immensely. However, relatively few of these studies have situated their findings within the institutional, political, organizational and governmental (IPOG) context in which interventions and outcomes exist. This conceptual mapping scoping study synthesized the published literature on the impact of IPOG factors on epidemic and pandemic response and critically examined definitions and uses of the terms IPOG in this literature. This research involved a comprehensive search of four databases across the social, health and biomedical sciences as well as …

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

Results: Parents noted several motivations …

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

Center for Medical Ethics and Health Policy Staff Publications

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

Detection And Characterization Of Constitutive Replication Origins Defined By Dna Polymerase Epsilon, Roman Jaksik, David A Wheeler, Marek Kimmel

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite the process of DNA replication being mechanistically highly conserved, the location of origins of replication (ORI) may vary from one tissue to the next, or between rounds of replication in eukaryotes, suggesting flexibility in the choice of locations to initiate replication. Lists of human ORI therefore vary widely in number and location, and there are currently no methods available to compare them. Here, we propose a method of detection of ORI based on somatic mutation patterns generated by the mutator phenotype of damaged DNA polymerase epsilon (POLE).

Results: We report the genome-wide localization of constitutive ORI in POLE-mutated …

Effortful Control Moderates The Relation Between Negative Emotionality And Child Anxiety And Depressive Symptom Severity In Children With Anxiety Disorders, Elizabeth M Raines, Andres G Viana, Erika S Trent, Haley E Conroy, Karina Silva, Michael J Zvolensky, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

The present study investigated the interactive effect of reactive (negative emotionality) and regulatory (effortful control) aspects of temperament in the prediction of child anxiety and depressive symptoms. Clinically anxious children and their mothers completed a battery of questionnaires that included self- and mother-ratings of child effortful control, negative emotionality, anxiety, and depressive symptoms. Multiple regression analyses were conducted to examine the moderating effect of effortful control on the relation between negative emotionality and child anxiety and depressive symptom severity. The interaction between negative emotionality and effortful control was statistically significant and simple slopes revealed that as effortful control increased, the …

A Phase Ii Window Of Opportunity Study Of Neoadjuvant Pd-L1 Versus Pd-L1 Plus Ctla-4 Blockade For Patients With Malignant Pleural Mesothelioma, Hyun-Sung Lee, Hee-Jin Jang, Maheshwari Ramineni, Daniel Y Wang, Daniela Ramos, Jong Min Choi, Taylor Splawn, Monica Espinoza, Michelle Almarez, Leandria Hosey, Eunji Jo, Susan Hilsenbeck, Christopher I Amos, R Taylor Ripley, Bryan M Burt

Center for Medical Ethics and Health Policy Staff Publications

Purpose: We report the results of a phase II, randomized, window-of-opportunity trial of neoadjuvant durvalumab versus durvalumab plus tremelimumab followed by surgery in patients with resectable malignant pleural mesothelioma (MPM; NCT02592551).

Patients and methods: The primary objective was alteration of the intratumoral CD8/regulatory T cell (Treg) ratio after combination immune checkpoint blockade (ICB) therapy. Secondary and exploratory objectives included other changes in the tumor microenvironment, survival, safety, tumor pathologic response (PR), and systemic immune responses.

Results: Nine patients received monotherapy and 11 received combination therapy. Seventeen of the 20 patients (85%) receiving ICB underwent planned thoracotomy. Both ICB regimens …

Effect Of Hiv And Antiretroviral Therapy Use On Body Weight Changes In A Cohort Of Us Veterans Living With And Without Hiv, Jose M Garcia, Yongquan Dong, Peter Richardson, Jennifer R Kramer, Christine M Hartman, Kathryn Royse, Donna L White, Elizabeth Y Chiao

Center for Medical Ethics and Health Policy Staff Publications

Objective: People living with HIV have high rates of obesity and obesity-related comorbidities. Our study sought to evaluate weight trajectory in a retrospective cohort of people living with HIV and matched HIV-negative veterans (controls) and to evaluate risk factors for weight gain.

Methods: This was a retrospective database analysis of data extracted from the VA Corporate Data Warehouse that included people living with HIV (n = 22 421) and age-matched HIV-negative controls (n = 63 072). The main outcomes were baseline body weight and weight change from baseline at 1, 2, and 5 years after diagnosis (baseline visit for controls). …

Enhancing Reciprocity, Equity And Quality Of Ethics Review For Multisite Research During Public Health Crises: The Experience Of The Covid-19 Clinical Research Coalition Ethics Working Group, Vasiliki Rahimzadeh, Jennyfer Ambe, Jantina De Vries

Center for Medical Ethics and Health Policy Staff Publications

In this paper we report findings from a commissioned report to the COVID-19 Clinical Research Coalition on approaches to streamline multinational REC review/approval during public health emergencies. As currently envisioned in the literature, a system of REC mutual recognition is theoretically possible based on shared procedural REC standards, but raises numerous concerns about perceived inequities and mistrust.

Clinician Perceptions Of Passport For Care, A Web-Based Clinical Decision Support Tool For Survivorship Care Plan Delivery, Jason E King, Michael C O'Connor, Ellen Shohet, Susan M Krause, Michael E Scheurer, Marc E Horowitz, David G Poplack, C Michael Fordis, Maria M Gramatges

Center for Medical Ethics and Health Policy Staff Publications

Background: The Children's Oncology Group Long-Term Follow-Up Guidelines provide exposure-based risks and recommendations for late effects screening of survivors of childhood cancer. Passport for Care (PFC) is a web-based clinical decision support tool for generating a personalized survivorship care plan (SCP) derived from the Guidelines and user-entered exposures. We assessed PFC clinician user practices and perceptions of PFC impact on clinic workflow, guidelines application, and survivor shared decision-making.

Procedure: A 35-item REDCap survey was emailed to all PFC users (n = 936) in 146 current and former PFC user clinics. Anonymous responses were permitted. Results were summarized and compared with …

Treatment And Life Goals Among Veterans With Gulf War Illness, Nicole Sullivan, Hannah Schorpp, Sarah Crosky, Scott Thien, Drew A Helmer, David R Litke, Wilfred R Pigeon, Karen S Quigley, Lisa M Mcandrew

Center for Medical Ethics and Health Policy Staff Publications

Medically unexplained syndromes (MUS), also termed persistent physical symptoms, are both prevalent and disabling. Yet treatments for MUS are marked by high rates of patient dissatisfaction, as well as disagreement between patients and providers on the management of persistent physical symptoms. A better understanding of patient-generated goals could increase collaborative goal setting and promote person-centered care, a critical component of MUS treatment; yet research in this area is lacking. This paper aimed to develop a typology of treatment and life goals among Gulf War veterans with a medically unexplained syndrome (Gulf War Illness). We examined participants’ responses to open-ended questions …

The Shortfalls Of Vulnerability Indexes For Public Health Decision-Making In The Face Of Emergent Crises: The Case Of Covid-19 Vaccine Uptake In Virginia, Lydia Cleveland Sa, Erika Frydenlund

VMASC Publications

Equitable and effective vaccine uptake is a key issue in addressing COVID-19. To achieve this, we must comprehensively characterize the context-specific socio-behavioral and structural determinants of vaccine uptake. However, to quickly focus public health interventions, state agencies and planners often rely on already existing indexes of "vulnerability." Many such "vulnerability indexes" exist and become benchmarks for targeting interventions in wide ranging scenarios, but they vary considerably in the factors and themes that they cover. Some are even uncritical of the use of the word "vulnerable," which should take on different meanings in different contexts. The objective of this study is …

Community Engagement In Precision Medicine Research: Organizational Practices And Their Impacts For Equity, Janet K Shim, Nicole Foti, Emily Vasquez, Stephanie M Fullerton, Michael Bentz, Melanie Jeske, Sandra Soo-Jin Lee

Center for Medical Ethics and Health Policy Staff Publications

Background: In the wake of mandates for biomedical research to increase participation by members of historically underrepresented populations, community engagement (CE) has emerged as a key intervention to help achieve this goal.

Methods: Using interviews, observations, and document analysis, we examine how stakeholders in precision medicine research understand and seek to put into practice ideas about who to engage, how engagement should be conducted, and what engagement is for.

Results: We find that ad hoc, opportunistic, and instrumental approaches to CE exacted significant consequences for the time and resources devoted to engagement and the ultimate impacts it has on research. …

Using Visual Arts Education And Reflective Practice To Increase Empathy And Perspective Taking In Medical Students, Sina Rezaei, Andrew Childress, Bhavika Kaul, Kelly Magill Rosales, Alana Newell, Stacey Rose

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Empathy is a critical competency for health care providers. However, empathy levels in medical students and residents have been shown to paradoxically decrease during training. Arts and humanities education and reflective practice may reduce burnout and promote empathy during medical school.

Methods: We developed and implemented an art education elective for medical students focusing on observation and reflective practice and measured its impact on empathy. Between 2017 and 2022, first-year medical students were offered an annual, 4-week elective led by art educators that featured visualization exercises and discussions on the role of bias and perspective in art interpretation. Curriculum …

Renewed Calls For Abortion-Related Research In The Post-Roe Era, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

“Extremely Slow And Capricious”: A Qualitative Exploration Of Genetic Researcher Priorities In Selecting Shared Data Resources, M Grace Trinidad, Kerry A Ryan, Chris D Krenz, J Scott Roberts, Amy L Mcguire, Raymond De Vries, Brian J Zikmund-Fisher, Sharon Kardia, Erica Marsh, Jane Forman, Madison Kent, David Wilborn, Kayte Spector-Bagdady

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Genetic researchers' selection of a database can have scientific, regulatory, and ethical implications. It is important to understand what is driving database selection such that database stewards can be responsive to user needs while balancing the interests of communities in equitably benefiting from advances.

Methods: We conducted 23 semistructured interviews with US academic genetic researchers working with private, government, and collaboratory data stewards to explore factors that they consider when selecting a genetic database.

Results: Interviewees used existing databases to avoid burdens of primary data collection, which was described as expensive and time-consuming. They highlighted ease of access as …

Deep Brain Stimulation For Pediatric Dystonia: Clinicians' Perspectives On The Most Pressing Ethical Challenges, Kristin M Kostick-Quenet, Lavina Kalwani, Laura N Torgerson, Katrina Munoz, Clarissa Sanchez, Eric A Storch, J S Blumenthal-Barby, Gabriel Lazáro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Pediatric deep brain stimulation (pDBS) is commonly used to manage treatment-resistant primary dystonias with favorable results and more frequently used for secondary dystonia to improve quality of life. There has been little systematic empirical neuroethics research to identify ethical challenges and potential solutions to ensure responsible use of DBS in pediatric populations.

Methods: Clinicians (n = 29) who care for minors with treatment-resistant dystonia were interviewed for their perspectives on the most pressing ethical issues in pDBS.

Results: Using thematic content analysis to explore salient themes, clinicians identified four pressing concerns: (1) uncertainty about risks and benefits of pDBS …

Validation Of A Process For Shared Decision-Making In Pediatrics, Douglas J Opel, Holly Hoa Vo, Nicolas Dundas, Heather Spielvogle, Amanda Mercer, Benjamin S Wilfond, Jonna Clark, Carrie L Heike, Elliott M Weiss, Mersine A Bryan, Seema K Shah, Carolyn A Mccarty, Jeffrey D Robinson, Jennifer Blumenthal-Barby, Jon Tilburt

Center for Medical Ethics and Health Policy Staff Publications

OBJECTIVE: We sought to confirm, refute, or modify a 4-step process for implementing shared decision-making (SDM) in pediatrics that involves determining 1) if the decision includes >1 medically reasonable option; 2) if one option has a favorable medical benefit-burden ratio compared to other options; and 3) parents' preferences regarding the options; then 4) calibrating the SDM approach based on other relevant decision characteristics.

METHODS: We videotaped a purposive sample of pediatric inpatient and outpatient encounters at a single US children's hospital. Clinicians from 7 clinical services (craniofacial, neonatology, oncology, pulmonary, pediatric intensive care, hospital medicine, and sports medicine) were eligible. …

Figg At 5: An Update On Us Public Perspectives On Forensic Investigative Genetic Genealogy Five Years After Its Introduction To Criminal Investigations, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

Covid-19 Vaccines: The Imperfect Instruments Of Vaccine Diplomacy, Peter J Hotez

Center for Medical Ethics and Health Policy Staff Publications

Although true vaccine diplomacy in the form of sharing vaccine development technologies and scientific cooperation with low- and middle-income countries has not been a dominant theme in the COVID-19 pandemic, this aspect is now taking off and generating some exciting new possibilities.

Association Of Gulf War Illness With Characteristics In Deployed Vs Non-Deployed Gulf War Era Veterans In The Cooperative Studies Program 2006/Million Veteran Program 029 Cohort: A Cross-Sectional Analysis, Linh M Duong, Alice B S Nono Djotsa, Jacqueline Vahey, Lea Steele, Rachel Quaden, Kelly M Harrington, Sarah T Ahmed, Renato Polimanti, Elani Streja, John Michael Gaziano, John Concato, Hongyu Zhao, Krishnan Radhakrishnan, Elizabeth R Hauser, Drew A Helmer, Mihaela Aslan, Elizabeth J Gifford

Center for Medical Ethics and Health Policy Staff Publications

Gulf War Illness (GWI), a chronic multisymptom illness with a complex and uncertain etiology and pathophysiology, is highly prevalent among veterans deployed to the 1990-1991 GW. We examined how GWI phenotypes varied by demographic and military characteristics among GW-era veterans. Data were from the VA's Cooperative Studies Program 2006/Million Veteran Program (MVP) 029 cohort, Genomics of GWI. From June 2018 to March 2019, 109,976 MVP enrollees (out of a total of over 676,000) were contacted to participate in the 1990-1991 GW-era Survey. Of 109,976 eligible participants, 45,169 (41.1%) responded to the 2018-2019 survey, 35,902 respondents met study inclusion criteria, 13,107 …

Factors Associated With A Diagnosis Of Sarcoidosis Among Us Veterans Of Iraq And Afghanistan, Nisha Jani, Israel C Christie, Tianshi David Wu, Daniel E Guzman, Jaehwan Han, Bryan Broderick, Michael J Falvo, Anays Sotolongo, Omowunmi Y Osinubi, Drew A Helmer

Center for Medical Ethics and Health Policy Staff Publications

This study evaluated risk factors of sarcoidosis among Airborne Hazards and Open Burn Pit Registry (AHOBPR) participants using a retrospective age and sex-matched case-control design of AHOBPR participants deployed to Afghanistan or Southwest Asia with and without sarcoidosis diagnosed in the Veterans Health Administration (VHA). Logistic regression models tested for associations between sarcoidosis and self-reported cumulative deployment-related exposures. 661 Veterans (0.37%) were diagnosed with sarcoidosis in VHA. Logistic regression demonstrated lower odds of sarcoidosis in Hispanic participants (OR 0.08, CI 0.04-0.15) and those who served in the Navy (OR 0.40, CI 0.21-0.72). African American veterans (OR 2.27, CI 1.66-3.11) and …

Malnutrition Vaccines For An Imminent Global Food Catastrophe, Peter J Hotez

Center for Medical Ethics and Health Policy Staff Publications

Together with climate change, both the geopolitical events in Ukraine and social disruptions in supply chains from the COVID-19 pandemic could produce global food shortages or even mass starvation events. Promising new interventions include vaccines to prevent infectious causes of malnutrition or infections disproportionately causing death among the malnourished.

Lack Of Consensus Among Healthcare Professionals At A Large Academic Medical Center On The Use Of Exome Sequencing For Prenatal Diagnosis, Kylie Johnson, Hadi Erfani, Mohamad Ali Maktabi, Ignatia Van Den Veyver, Salma Nassef

Center for Medical Ethics and Health Policy Staff Publications

Prenatal exome sequencing (ES) is increasingly used for prenatal diagnosis because emerging data indicate it has incremental diagnostic benefit in pregnancies with fetal anomalies without identified genetic abnormalities by karyotyping and chromosomal microarray analysis. The aim of this study was to evaluate the medical community's attitude toward the clinical utility and use of exome sequencing for prenatal diagnosis and to address differences in attitudes and responses by type of practitioner, level of training, and years passed since last full-time training. We analyzed the answers of 109 trainees and professionals in the fields of genetic counseling, laboratory science, and medicine to …

Effect Of Problem-Solving Treatment On Self-Reported Disability Among Veterans With Gulf War Illness: A Randomized Clinical Trial, Lisa M Mcandrew, Karen S Quigley, Shou-En Lu, David Litke, Joseph F Rath, Gudrun Lange, Susan L Santos, Nicole Anastasides, Beth Ann Petrakis, Lauren Greenberg, Drew A Helmer, Wilfred R Pigeon

Center for Medical Ethics and Health Policy Staff Publications

Importance: Few evidence-based treatments are available for Gulf War illness (GWI). Behavioral treatments that target factors known to maintain the disability from GWI, such as problem-solving impairment, may be beneficial. Problem-solving treatment (PST) targets problem-solving impairment and is an evidence-based treatment for other conditions.

Objective: To examine the efficacy of PST to reduce disability, problem-solving impairment, and physical symptoms in GWI.

Design, setting, and participants: This multicenter randomized clinical trial conducted in the US Department of Veterans Affairs compared PST with health education in a volunteer sample of 511 Gulf War veterans with GWI and disability (January 1, 2015, to …

Clinical And Demographic Factors Contributing To Asparaginase-Associated Toxicities In Children With Acute Lymphoblastic Leukemia, Priyadarshani Dharia, Michael D Swartz, M Brooke Bernhardt, Han Chen, M Monica Gramatges, Philip J Lupo, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; …

Phase I Car-T Clinical Trials Review, Shaun Bulsara, Mengfen Wu, Tao Wang

Center for Medical Ethics and Health Policy Staff Publications

Background/aim: Chimeric antigen receptor (CAR) T cells with tumor specificity are being increasingly investigated. Phase I trials are the first step of testing for safety of novel CAR-T therapy to determine the maximum tolerated dose (MTD). Several dose escalation methods have been developed over time including rule-based, model-based, and model-assisted designs. The goal of this project is to overview the phase I designs used in current CAR-T trials.

Materials and methods: We searched PubMed for peer-reviewed literature published between January 1, 2015 and December 31, 2021. The search was limited to human studies in the English language using the keywords …

Germline Genetic And Treatment-Related Risk Factors For Diabetes Mellitus In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study And St Jude Lifetime Cohorts, Melissa A Richard, Sogol Mostoufi-Moab, Nisha Rathore, Jessica Baedke, Austin L Brown, Stephen J Chanock, Danielle N Friedman, M Monica Gramatges, Rebecca M Howell, Kala Y Kamdar, Wendy M Leisenring, Lillian R Meacham, Lindsay M Morton, Kevin Oeffinger, Leslie L Robison, Yadav Sapkota, Charles A Sklar, Gregory T Armstrong, Smita Bhatia, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Purpose: To characterize germline genetic risk factors of diabetes mellitus among long-term survivors of childhood cancer.

Methods: Adult survivors of childhood cancer from the Childhood Cancer Survivor Study (CCSS) Original Cohort (n = 5,083; 383 with diabetes) were used to conduct a discovery genome-wide association study. Replication was performed using the CCSS Expansion (n = 2,588; 40 with diabetes) and the St Jude Lifetime (SJLIFE; n = 3,351; 208 with diabetes) cohorts. Risk prediction models, stratified on exposure to abdominal radiation, were calculated using logistic regression including attained age, sex and body mass index, diagnosis, alkylating chemotherapy, age at cancer …

Prenatal Phenotyping Of Fetal Tubulinopathies: A Multicenter Retrospective Case Series, Bobby K Brar, Marisa Gilstrop Thompson, Neeta L Vora, Kelly Gilmore, Karin Blakemore, Kristen A Miller, Jessica Giordano, Andreas Dufke, Beatrix Wong, Samantha Stover, Billie Lianoglou, Ignatia Van Den Veyver, Esther Dempsey, Mara Rosner, Karen Chong, David Chitayat, Teresa N Sparks, Mary E Norton, Ronald Wapner, Kristin Baranano, Angie C Jelin, Fetal Sequencing Consortium

Center for Medical Ethics and Health Policy Staff Publications

Objective: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.

Methods: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.

Results: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings …

Incidence Of An Insulin-Requiring Hyperglycemic Syndrome In Sars-Cov-2-Infected Young Individuals: Is It Type 1 Diabetes?, Massimo Pietropaolo, Peter Hotez, Nick Giannoukakis

Center for Medical Ethics and Health Policy Staff Publications

Pancreatic ACE2 receptor expression, together with increased prevalence of insulin-requiring hyperglycemia in patients with coronavirus disease 2019 (COVID-19), suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pancreatic infection might trigger a β-cell-selective inflammation precipitating autoimmune type 1 diabetes (T1D). We examined T1D incidence in patients with COVID-19 inside a large, global population using a "big data" approach. The incidence in 0-30-year-old patients with confirmed COVID-19 over an ∼15-month period from the beginning of the COVID-19 pandemic was compared with an age-matched population without COVID-19 inside the TriNetX COVID-19 Research Network (>80 million deidentified patient electronic medical records globally). …