Bioethics and Medical Ethics Commons^™

Is Detection Of Relapse By Surveillance Imaging Associated With Longer Survival In Patients With Rhabdomyosarcoma?, Stephanie Fetzko, Adriana Fonseca, Mary Frances Wedekind, Abha A Gupta, Bhuvana A Setty, Jeremy Schraw, Philip J Lupo, Robert P Guillerman, Anish A Butala, Heidi Russell, Lauren Nicholls, David Walterhouse, Douglas S Hawkins, Mehmet F Okcu

Center for Medical Ethics and Health Policy Staff Publications

Background: We investigated whether surveillance imaging had an impact on post-relapse survival in patients with rhabdomyosarcoma (RMS). We hypothesized that relapse detected by imaging (group IM) would be associated with longer survival compared with relapse detected with a clinical sign or symptom (group SS).

Materials and methods: We performed an observational multi-institutional study in 127 patients with relapsed RMS comparing overall survival (OS) after relapse using Kaplan-Meier and Cox proportional hazards analyses.

Results: Relapse was detected in 60 (47%) group IM and 67 (53%) SS patients. Median follow-up in survivors was 4 years (range 1.0 to 16.7 y). Four-year OS …

Addressing Human Trafficking As A Public Health Issue, Frances Recknor, Erica Di Ruggiero, Elsabeth Jensen

Center for Medical Ethics and Health Policy Staff Publications

Human trafficking is increasingly recognized as a significant global public health issue. Human trafficking (HT) exists in all nations, including Canada, and is estimated to impact 25 million people globally. HT is a crime that is not always visible. It is associated with a myriad of deleterious health outcomes arising from adverse living and working conditions, and the physical, sexual, and/or psychological violence often accompanying it. Human trafficking also disproportionately affects people living under vulnerable circumstances, particularly those with intersecting vulnerabilities. Public health can advance health equity for trafficked persons and add value to existing anti-trafficking (AT) efforts. Among its …

Sexual Health Assessment Is Vital To Whole Health Models Of Care, Alex Uzdavines, Drew A Helmer, Juliette F Spelman, Kristin M Mattocks, Amanda M Johnson, John F Chardos, Kristine E Lynch, Michael R Kauth

Center for Medical Ethics and Health Policy Staff Publications

Sexual health is the state of well-being regarding sexuality. Sexual health is highly valued and associated with overall health. Overall health and well-being are more than the absence of disease or dysfunction. Health care systems adopting whole health models of care need to incorporate a holistic assessment of sexual health. This includes assessing patients' sexual orientation and gender identity (SOGI). If health systems, including but not limited to the Veterans Health Administration (VHA), incorporate sexual health into whole health they could enhance preventive care, promote healthy sexual functioning, and optimize overall health and well-being. Assessing sexual health can give providers …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma, Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Center for Medical Ethics and Health Policy Staff Publications

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

Therapeutic Targeting Of Macrophage Plasticity Remodels The Tumor-Immune Microenvironment, Hee-Jin Jang, Hyun-Sung Lee, Wendong Yu, Maheshwari Ramineni, Cynthia Y Truong, Daniela Ramos, Taylor Splawn, Jong Min Choi, Sung Yun Jung, Ju-Seog Lee, Daniel Y Wang, Joel M Sederstrom, Massimo Pietropaolo, Farrah Kheradmand, Christopher I Amos, Thomas M Wheeler, R Taylor Ripley, Bryan M Burt

Center for Medical Ethics and Health Policy Staff Publications

Although the majority of patients with advanced lung adenocarcinoma (LUAD) are eligible to receive immune checkpoint blockade, approximately 80% of these tumors are resistant to this therapeutic approach. Insights at the single-cell level into mechanisms that drive LUAD tumorigenesis and the relationship of LUAD histologic heterogeneity to response to immune checkpoint blockade could help identify biomarkers and potential combinational approaches to improve immunotherapy efficacy. Here we used a genetically engineered mouse model that replicates the development of human LUAD through a spectrum of pre-invasive to invasive adenocarcinoma histologic subtypes. A systems onco-immunology approach of integrating the analytical power and unique, …

An Updated Assessment Of 43,110 Patients Enrolled In The Childhood Cancer Research Network: A Children’S Oncology Group Report, Austin L Brown, Pagna Sok, Michael E Scheurer, Karen R Rabin, Erin L Marcotte, Douglas S Hawkins, Logan G Spector, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment.

Method: The number of US childhood patients with cancer diagnosed < 20 years of age enrolled in CCRN (2008-2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates. Observed-to-expected ratios and corresponding 95% confidence intervals (CI) were estimated across sex, race, diagnosis age, calendar year, and cancer diagnosis groups. Multivariable linear regression models were generated to evaluate the association between open COG phase 3 therapeutic trials and CCRN enrollment rates.

Result: The 43,110 cases enrolled in CCRN represented 36% of the expected childhood cancers diagnosed from 2008 to 2015 (N = 120,118). CCRN enrollment ratios [95% CI] were highest among males (0.38 [95% CI, 0.37-0.38]), non-Hispanics (0.35 [95% CI, 0.35-0.36]), and those diagnosed from 1 to 4 years …

Actionable Tumor Alterations And Treatment Protocol Enrollment Of Pediatric And Young Adult Patients With Refractory Cancers In The National Cancer Institute-Children's Oncology Group Pediatric Match Trial, D Williams Parsons, Katherine A Janeway, David R Patton, Cynthia L Winter, Brent Coffey, P Mickey Williams, Sinchita Roy-Chowdhuri, Gregory J Tsongalis, Mark Routbort, Nilsa C Ramirez, Lauren Saguilig, Jin Piao, Todd A Alonzo, Stacey L Berg, Elizabeth Fox, Douglas S Hawkins, Jeffrey S Abrams, Margaret Mooney, Naoko Takebe, James V Tricoli, Nita L Seibel, Nci-Cog Pediatric Match Team

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial aimed to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations.

Patients and methods: Tumors from patients age 1-21 years with refractory solid tumors, lymphomas, or histiocytic disorders were subjected to cancer gene panel sequencing and limited immunohistochemistry to identify actionable alterations for assignment to phase II treatment arms. The rates of treatment arm assignment and enrollment were compared between clinical and demographic groups.

Results: Testing was completed for 94.7% of tumors submitted. Actionable alterations were detected …

Phase Ii Study Of Selumetinib In Children And Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E Of The Nci-Cog Pediatric Match Trial, Olive S Eckstein, Carl E Allen, P Mickey Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Nilsa C Ramirez, Alok Jaju, Joyce Mhlanga, Elizabeth Fox, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D Williams Parsons

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib.

Methods: Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib.

Results: Twenty patients (median age: 14 …

Assessing Smoking Status And Risk Of Sars-Cov-2 Infection: A Machine Learning Approach Among Veterans, Alice B S Nono Djotsa, Drew A Helmer, Catherine Park, Kristine E Lynch, Amir Sharafkhaneh, Aanand D Naik, Javad Razjouyan, Christopher I Amos

Center for Medical Ethics and Health Policy Staff Publications

The role of smoking in the risk of SARS-CoV-2 infection is unclear. We used a retrospective cohort design to study data from veterans' Electronic Medical Record to assess the impact of smoking on the risk of SARS-CoV-2 infection. Veterans tested for the SARS-CoV-2 virus from 02/01/2020 to 02/28/2021 were classified as: Never Smokers (NS), Former Smokers (FS), and Current Smokers (CS). We report the adjusted odds ratios (aOR) for potential confounders obtained from a cascade machine learning algorithm. We found a 19.6% positivity rate among 1,176,306 veterans tested for SARS-CoV-2 infection. The positivity proportion among NS (22.0%) was higher compared …

Provider Perceptions Of Telehealth And In-Person Exposure And Response Prevention For Obsessive-Compulsive Disorder, Andrew D Wiese, Kendall N Drummond, Madeleine N Fuselier, Jessica C Sheu, Gary Liu, Andrew G Guzick, Wayne K Goodman, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Until recently, psychotherapies, including exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD), have primarily been delivered in-person. The COVID-19 pandemic required OCD providers delivering ERP to quickly transition to telehealth services. While evidence supports telehealth ERP delivery, limited research has examined OCD provider perceptions about patient characteristics that are most appropriate for this modality, as well as provider abilities to identify and address factors interfering with effective telehealth ERP. In the present study, OCD therapists (N = 113) rated the feasibility of delivering telehealth ERP relative to in-person for different (1) patient age-groups, (2) levels of OCD severity, and …

Breast Cancer Diagnosis And Treatment During The Covid-19 Pandemic In A Nationwide, Insured Population, Jennifer L Caswell-Jin, Maryam N Shafaee, Lan Xiao, Mina Liu, Esther M John, Melissa L Bondy, Allison W Kurian

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The early months of the COVID-19 pandemic led to reduced cancer screenings and delayed cancer surgeries. We used insurance claims data to understand how breast cancer incidence and treatment after diagnosis changed nationwide over the course of the pandemic.

Methods: Using the Optum Research Database from January 2017 to March 2021, including approximately 19 million US adults with commercial health insurance, we identified new breast cancer diagnoses and first treatment after diagnosis. We compared breast cancer incidence and proportion of newly diagnosed patients receiving pre-operative systemic therapy pre-COVID, in the first 2 months of the COVID pandemic and in …

The Role Of An Inpatient Hospice And Palliative Clinical Pharmacist In The Interdisciplinary Team, Jetavia Jones Moody, Ivy O Poon, Ursula K Braun

Center for Medical Ethics and Health Policy Staff Publications

Palliative care is a specialized health care service for individuals with serious illness at any stage and can be provided in any setting. Current national consensus developed by palliative care experts recommends the inclusion of pharmacists in an interdisciplinary team (IDT) to provide quality palliative care. However, national registry data report that less than 10% of inpatient palliative teams in the U.S. have a clinical pharmacist. Clinical pharmacists have an impactful role in palliative patients' quality of life by optimizing symptom management, deprescribing, and providing education to the palliative care team as well as patients and their families. In this …

A Novel, De Novo Intronic Variant In Pogz Causes White-Sutton Syndrome, Ashanta Merriweather, David R Murdock, Jill A Rosenfeld, Hongzheng Dai, Shamika Ketkar, Lisa Emrick, Sarah Nicholas, Richard A Lewis, Undiagnosed Diseases Network, Carlos A Bacino, Daryl A Scott, Brendan Lee, Vernon Reid Sutton, Lorraine Potocki, Lindsay C Burrage

Center for Medical Ethics and Health Policy Staff Publications

White-Sutton syndrome (WHSUS), which is caused by heterozygous pathogenic variants in POGZ, is characterized by a spectrum of intellectual disabilities and global developmental delay with or without features of autism spectrum disorder. Additional features may include hypotonia, behavioral abnormalities, ophthalmic abnormalities, hearing loss, sleep apnea, microcephaly, dysmorphic facial features, and rarely, congenital diaphragmatic hernia (CDH). We present a 6-year-old female with features of WHSUS, including CDH, but with nondiagnostic clinical trio exome sequencing. Exome sequencing reanalysis revealed a heterozygous, de novo, intronic variant in POGZ (NM_015100.3:c.2546-20T>A). RNA sequencing revealed that this intronic variant leads to skipping of exon 18. …

A Validation Framework For Somatic Copy Number Detection In Targeted Sequencing Panels, Raghu Chandramohan, Jacquelyn Reuther, Ilavarasi Gandhi, Horatiu Voicu, Karla R Alvarez, Sharon E Plon, Dolores H Lopez-Terrada, Kevin E Fisher, D Williams Parsons, Angshumoy Roy

Center for Medical Ethics and Health Policy Staff Publications

Somatic copy number alterations (SCNAs) in tumors are clinically significant diagnostic, prognostic, and predictive biomarkers. SCNA detection from targeted next-generation sequencing panels is increasingly common in clinical practice; however, detailed descriptions of optimization and validation of SCNA pipelines for small targeted panels are limited. This study describes the validation and implementation of a tumor-only SCNA pipeline using CNVkit, augmented with custom modules and optimized for clinical implementation by testing reference materials and clinical tumor samples with different classes of copy number variation (CNV; amplification, single copy loss, and biallelic loss). Using wet-bench and in silico methods, various parameters impacting CNV …

Post-Trial Access In Implanted Neural Device Research: Device Maintenance, Abandonment, And Cost, Gabriel Lázaro-Muñoz, Michelle T Pham, Katrina A Muñoz, Kristin Kostick-Quenet, Clarissa E Sanchez, Laura Torgerson, Jill Robinson, Stacey Pereira, Simon Outram, Barbara A Koenig, Philip A Starr, Aysegul Gunduz, Kelly D Foote, Michael S Okun, Wayne Goodman, Amy L Mcguire, Peter Zuk

Center for Medical Ethics and Health Policy Staff Publications

Background: Clinical trial participants who benefit from experimental neural devices for the treatment of debilitating and otherwise treatment-resistant conditions are generally not ensured continued access to effective therapy or maintenance of devices at the conclusion of trials.

Objective/hypothesis: Post-trial obligations have been extensively examined in the context of drug trials, but there has been little empirical examination of stakeholder perspectives regarding these obligations in the rapidly growing field of neural device research.

Methods: This study examined the perspectives of 44 stakeholders (i.e., 23 researchers and 21 patient-participants) involved in implantable neural device trials.

Results: Researchers were concerned about current post-trial …

Creation Of A Global Vaccine Risk Index, Tasmiah Nuzhath, Peter J Hotez, Ashish Damania, P Shuling Liu, Brian Colwell

Center for Medical Ethics and Health Policy Staff Publications

The World Health Organization has identified vaccine hesitancy as one of its top ten global health threats for 2019. Efforts are underway to define the factors responsible for reductions in vaccine confidence. However, as global measles cases accelerated beginning in 2018, it became evident that additional factors were promoting measles re-emergence, including war, political and socio-economic collapse, shifting poverty, and vulnerability to weather events and climate change. Accordingly, we propose a Global Vaccine Risk Index (VRI) to consider these variables as a more comprehensive means to identify vulnerable nations where we might expect measles and other vaccine-preventable diseases to emerge …

Creating A Collaborative Trauma-Informed Interdisciplinary Citywide Victim Services Model Focused On Health Care For Survivors Of Human Trafficking, Juhi Jain, Mackenzie Bennett, Mark D Bailey, Daniel Liaou, Sheri-Ann O Kaltiso, Jordan Greenbaum, Kimberly Williams, Mollie R Gordon, Melissa I M Torres, Phuong T Nguyen, John H Coverdale, Victor Williams, Cayla Hari, Samantha Rodriguez, Temilola Salami, Jonell E Potter

Center for Medical Ethics and Health Policy Staff Publications

Although human trafficking is recognized as a public health issue, research on the health effects of human trafficking and best intervention practices is limited. We describe 2 citywide collaborative victim services models, the THRIVE (Trafficking, Healthcare, Resources, and Interdisciplinary Victim Services and Education) Clinic at the University of Miami and Jackson Health System in Miami, Florida, and the Greater Houston Area Pathways for Advocacy-based, Trauma-Informed Healthcare (PATH) Collaborative at Baylor College of Medicine, CommonSpirit Health, and San Jose Clinic in Houston, Texas, funded in part by the Office for Victims of Crime, which focus on trauma-informed health care delivery for …

Investigation Of Urinary Metabolomics In A Phase I Hookworm Vaccine Trial In Gabon, Madeleine Eunice Betouke Ongwe, Yoanne D Mouwenda, Koen A Stam, Peter G Kremsner, Bertrand Lell, David Diemert, Jeff Bethony, Maria E Bottazzi, Peter J Hotez, Remko V Leeuwen, Martin P Grobusch, Ayola A Adegnika, Oleg A Mayboroda, Maria Yazdanbakhsh

Center for Medical Ethics and Health Policy Staff Publications

Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes could be seen after vaccination in a phase I trial where Gabonese adults living either in rural or semi-urban areas received the subunit hookworm vaccine candidates (Na-GST-1 and Na-APR-1 (M74) adjuvanted with Alhydrogel plus GLA-AF (n = 24) or the hepatitis B vaccine (n = 8) as control. Urine samples were collected and assayed using targeted 1H NMR spectroscopy. At baseline, a set of metabolites significantly distinguished rural from semi-urban individuals. The pre- and post-vaccination comparisons indicated significant …

Fast Cbt For Pediatric Ocd: A Multiple-Baseline Controlled Pilot Trial Of Parent Training In Exposure And Response Prevention Delivered, Lara J Farrell, Natalja A Nabinger De Diaz, Sharna Mathieu, Matthew L Mckenzie, Taka Miyamoto, Caroline L Donovan, Allison M Waters, Sonja March, Nicole Bothma, Rianca Kroon, Gabrielle Simcock, Robert S Ware, Robert R Selles, Eric A Storch, Thomas Ollendick

Center for Medical Ethics and Health Policy Staff Publications

Objective: The current study utilized a single case series, non-concurrent multiple baseline design to examine the efficacy of training parents via telehealth videoconferencing in exposure and response prevention (ERP) for home delivery of the treatment for their children and adolescents with obsessive compulsive disorder (OCD).

Method: There were nine participants aged 8 to 14 years who had received a primary diagnosis of OCD. The design involved a series of AB replications, whereby following pre-treatment assessments participants were randomly assigned to either a 2-week (n = 4) or 3-week (n = 5) baseline condition with weekly monitoring of their …

A Mixed-Methods Protocol To Develop And Validate A Stewardship Maturity Matrix For Human Genomic Data In The Cloud, Vasiliki Rahimzadeh, Ge Peng, Mildred Cho

Center for Medical Ethics and Health Policy Staff Publications

This article describes a mixed-methods protocol to develop and test the implementation of a stewardship maturity matrix (SMM) for repositories which govern access to human genomic data in the cloud. It is anticipated that the cloud will host most human genomic and related health datasets generated as part of publicly funded research in the coming years. However, repository managers lack practical tools for identifying what stewardship outcomes matter most to key stakeholders as well as how to track progress on their stewardship goals over time. In this article we describe a protocol that combines Delphi survey methods with SMM modeling …