Public Affairs, Public Policy and Public Administration Commons^™

A Qualitative Interview Study To Determine Barriers And Facilitators Of Implementing Automated Decision Support Tools For Genomic Data Access, Vasiliki Rahimzadeh, Jinyoung Baek, Jonathan Lawson, Edward S Dove

Center for Medical Ethics and Health Policy Staff Publications

Data access committees (DAC) gatekeep access to secured genomic and related health datasets yet are challenged to keep pace with the rising volume and complexity of data generation. Automated decision support (ADS) systems have been shown to support consistency, compliance, and coordination of data access review decisions. However, we lack understanding of how DAC members perceive the value add of ADS, if any, on the quality and effectiveness of their reviews. In this qualitative study, we report findings from 13 semi-structured interviews with DAC members from around the world to identify relevant barriers and facilitators to implementing ADS for genomic …

Ethical Concerns For Remote Computer Perception In Cardiology: New Stages For Digital Health Technologies, Artificial Intelligence, And Machine Learning, Kristin Kostick-Quenet, Jerry Estep, Jennifer S Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Public Attitudes, Interests, And Concerns Regarding Polygenic Embryo Screening, Rémy A Furrer, Dorit Barlevy, Stacey Pereira, Shai Carmi, Todd Lencz, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Importance: Polygenic embryo screening (PES) is a novel technology that estimates the likelihood of developing future conditions (eg, diabetes or depression) and traits (eg, height or cognitive ability) in human embryos, with the goal of selecting which embryos to use. Given its commercial availability and concerns raised by researchers, clinicians, bioethicists, and professional organizations, it is essential to inform key stakeholders and relevant policymakers about the public's perspectives on this technology.

Objective: To survey US adults to examine general attitudes, interests, and concerns regarding PES use.

Design, setting, and participants: For this survey study, data were collected from 1 stratified …

Advancing Genomics To Improve Health Equity, Ebony B Madden, Lucia A Hindorff, Vence L Bonham, Tabia Henry Akintobi, Esteban G Burchard, Kellan E Baker, Rene L Begay, John D Carpten, Nancy J Cox, Valentina Di Francesco, Denise A Dillard, Faith E Fletcher, Stephanie M Fullerton, Nanibaa' A Garrison, Catherine M Hammack-Aviran, Vanessa Y Hiratsuka, James E K Hildreth, Carol R Horowitz, Chanita A Hughes Halbert, Michael Inouye, Amber Jackson, Latrice G Landry, Rick A Kittles, Jeff T Leek, Nita A Limdi, Nicole C Lockhart, Elizabeth O Ofili, Eliseo J Pérez-Stable, Maya Sabatello, Loren Saulsberry, Lorjetta E Schools, Jennifer L Troyer, Benjamin S Wilfond, Genevieve L Wojcik, Judy H Cho, Sandra S-J Lee, Eric D Green

Center for Medical Ethics and Health Policy Staff Publications

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in …

Patients’ And Physicians’ Beliefs And Attitudes Towards Integrating Personalized Risk Estimates Into Patient Education About Left Ventricular Assist Device Therapy, Kristin M Kostick-Quenet, Benjamin Lang, Natalie Dorfman, Jerry Estep, Mandeep R Mehra, Arvind Bhimaraj, Andrew Civitello, Ulrich Jorde, Barry Trachtenberg, Nir Uriel, Holland Kaplan, Eleanor Gilmore-Szott, Robert Volk, Mahwash Kassi, J S Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Background: Personalized risk (PR) estimates may enhance clinical decision making and risk communication by providing individualized estimates of patient outcomes. We explored stakeholder attitudes toward the utility, acceptability, usefulness and best-practices for integrating PR estimates into patient education and decision making about Left Ventricular Assist Device (LVAD).

Methods and results: As part of a 5-year multi-institutional AHRQ project, we conducted 40 interviews with stakeholders (physicians, nurse coordinators, patients, and caregivers), analyzed using Thematic Content Analysis. All stakeholder groups voiced positive views towards integrating PR in decision making. Patients, caregivers and coordinators emphasized that PR can help to better understand a …

Patient Interest In And Clinician Reservations On Polygenic Embryo Screening: A Qualitative Study Of Stakeholder Perspectives, D Barlevy, I Cenolli, T Campbell, R Furrer, M Mukherjee, K Kostick-Quenet, S Carmi, T Lencz, G Lázaro-Muñoz, S Pereira

Center for Medical Ethics and Health Policy Staff Publications

Purpose: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future.

Methods: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients.

Results: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally …

Parent-Led Cognitive Behavioral Teletherapy For Anxiety In Autistic Youth: A Randomized Trial Comparing Two Levels Of Therapist Support, Andrew G Guzick, Sophie C Schneider, Minjee Kook, Julia Rose Iacono, Saira A Weinzimmer, Troy Quast, Sean M Olsen, Killian Rainey Hughes, Emily Jellinek-Russo, Amanda Perozo Garcia, Abigail Candelari, Leandra N Berry, Robin P Goin-Kochel, Wayne K Goodman, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders, though to date it has been minimally tested. In this study, 87 autistic youth (7 to 13 years old) with anxiety disorders and their parents were randomized to two forms of parent-led CBT in which parents led their child through a guided CBT workbook across 12 weeks: one with low therapist contact (four 30-minute telehealth calls), and one with standard therapist contact (ten 60-minute telehealth calls). Anxiety, functional impairment, and autism features significantly declined across therapy, without …

Family Accommodation In Children And Adolescents With Misophonia, Eric A Storch, Andrew G Guzick, Johann D'Souza, Jane Clinger, Daphne Ayton, Minjee Kook, Conor Rork, Eleanor E Smith, Isabel A Draper, Nasim Khalfe, Catherine E Rast, Nicholas Murphy, Marijn Lijfijjt, Wayne K Goodman, Matti Cervin

Center for Medical Ethics and Health Policy Staff Publications

Family accommodation (e.g., reassurance, modifying routines, assisting avoidance) has not been explored among youth with misophonia but may have important clinical and intervention implications. We examined family accommodation in 102 children and adolescents with interview-confirmed misophonia and compared its frequency and content to family accommodation in 95 children and adolescents with anxiety disorders. Findings showed that family accommodation was ubiquitous in pediatric misophonia and may be even more frequent than in youth with anxiety disorders. Assisting the child, participating in misophonia-related behaviors, and modifying family routines were endorsed by more than 70% of parents of children with misophonia. Further, compared …

Direct Implantation Of Patient Brain Tumor Cells Into Matching Locations In Mouse Brains For Patient-Derived Orthotopic Xenograft Model Development, Lin Qi, Patricia Baxter, Mari Kogiso, Huiyuan Zhang, Frank K Braun, Holly Lindsay, Sibo Zhao, Sophie Xiao, Aalaa Sanad Abdallah, Milagros Suarez, Zilu Huang, Wan Yee Teo, Litian Yu, Xiumei Zhao, Zhigang Liu, Yulun Huang, Jack M Su, Tsz-Kwong Man, Ching C Lau, Laszlo Perlaky, Yuchen Du, Xiao-Nan Li

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models.

Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice.

Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% …

Harnessing Rna Technology To Advance Therapeutic Vaccine Antigens Against Chagas Disease, Chiara Mancino, Jeroen Pollet, Assaf Zinger, Kathryn M Jones, Maria José Villar, Ana Carolina Leao, Rakesh Adhikari, Leroy Versteeg, Rakhi Tyagi Kundu, Ulrich Strych, Federica Giordano, Peter J Hotez, Maria Elena Bottazzi, Francesca Taraballi, Cristina Poveda

Center for Medical Ethics and Health Policy Staff Publications

Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic disease endemic in 21 countries in South America, with increasing global spread. When administered late in the infection, the current antiparasitic drugs do not prevent the onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed the feasibility of developing an mRNA-based therapeutic CD vaccine targeting two known T. cruzi vaccine antigens (Tc24—a flagellar antigen and ASP-2—an amastigote antigen). We present the mRNA engineering steps, preparation, and stability of the lipid …

Evolution Of Telehealth-Its Impact On Palliative Care And Medication Management, Syed N Imam, Ursula K Braun, Mary A Garcia, Leanne K Jackson

Center for Medical Ethics and Health Policy Staff Publications

Palliative care plays a crucial role in enhancing the quality of life for individuals facing serious illnesses, aiming to alleviate suffering and provide holistic support. With the advent of telehealth, there is a growing interest in leveraging technology to extend the reach and effectiveness of palliative care services. This article provides a comprehensive review of the evolution of telehealth, the current state of telemedicine in palliative care, and the role of telepharmacy and medication management. Herein we highlight the potential benefits, challenges, and future directions of palliative telemedicine. As the field continues to advance, the article proposes key considerations for …

Analytical Challenges In Omics Research On Asthma And Allergy: A National Institute Of Allergy And Infectious Diseases Workshop, Supinda Bunyavanich, Patrice M Becker, Matthew C Altman, Jessica Lasky-Su, Carole Ober, Karsten Zengler, Evgeny Berdyshev, Richard Bonneau, Talal Chatila, Nilanjan Chatterjee, Kian Fan Chung, Colleen Cutcliffe, Wendy Davidson, Gang Dong, Gang Fang, Patricia Fulkerson, Blanca E Himes, Liming Liang, Rasika A Mathias, Shuji Ogino, Joseph Petrosino, Nathan D Price, Eric Schadt, James Schofield, Max A Seibold, Hanno Steen, Lisa Wheatley, Hongmei Zhang, Alkis Togias, Kohei Hasegawa

Center for Medical Ethics and Health Policy Staff Publications

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes …

The Role Of Between-Session Homework In Cognitive-Behavioral Therapy For Comorbid Obsessive-Compulsive Disorder And Autism: A Case Vignette, Molly J Church, Katie H Mangen, Jordan T Stiede, Samuel D Spencer, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Objective: Cognitive-behavioral therapy (CBT), which includes a decided emphasis on exposure and response/ritual prevention (ERP) and between-session practice of treatment principles, has consistently demonstrated efficacy for the treatment of obsessive-compulsive disorder (OCD) and is a gold standard, recommended first-line treatment. CBT with ERP has been successfully adapted to fit the needs of autistic individuals with OCD. The present article provides a brief overview of CBT for OCD and outlines special considerations and adaptations needed when working with patients with OCD and comorbid autism, with an emphasis on the importance of between-session homework.

Method: A case vignette is presented.

Results: This …

Data Stewardship In Ftld Research: Investigator And Research Participant Views, Jalayne J Arias, Ana M Tyler, Laura M Beskow, Maria C Carillo, Susan Dickinson, Jill Goldman, Mary A Majumder, Michelle M Mello, Heather M Snyder, Jennifer S Yokoyama

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Federal policies and guidelines have expanded the return of individual results to participants and expectations for data sharing between investigators and through repositories. Here, we report investigators' and study participants' views and experiences with data stewardship practices within frontotemporal lobal degeneration (FTLD) research, which reveal unique ethical challenges.

Methods: Semi-structured interviews with (1) investigators conducting FTLD research that includes genetic data collection and/or analysis and (2) participants enrolled in a single site longitudinal FTLD study.

Results: Analysis of the interviews identified three meta themes: perspectives on data sharing, experiences with enrollment and participation, and data management and security as …

Achieving Procedural Parity In Managing Access To Genomic And Related Health Data: A Global Survey Of Data Access Committee Members, Jonathan Lawson, Vasiliki Rahimzadeh, Jinyoung Baek, Edward S Dove

Center for Medical Ethics and Health Policy Staff Publications

Data access committees (DACs) are critical players in the data sharing ecosystem. DACs review requests for access to data held in one or more repositories and where specific constraints determine how the data may be used and by whom. Our team surveyed DAC members affiliated with genomic data repositories worldwide to understand standard processes and procedures, operational metrics, bottlenecks, and efficiencies, as well as their perspectives on possible improvements to quality review. We found that DAC operations and systemic issues were common across repositories globally. In general, DAC members endeavored to achieve an appropriate balance of review efficiency, quality, and …

Genetic Researchers' Use Of And Interest In Research With Diverse Ancestral Groups, Kaitlyn Jaffe, Amanda K Greene, Luyun Chen, Kerry A Ryan, Chris Krenz, J Scott Roberts, Brian J Zikmund-Fisher, Amy L Mcguire, J Denard Thomas, Erica E Marsh, Kayte Spector-Bagdady

Center for Medical Ethics and Health Policy Staff Publications

Importance: Genetic researchers must have access to databases populated with data from diverse ancestral groups to ensure research is generalizable or targeted for historically excluded communities.

Objective: To determine genetic researchers' interest in doing research with diverse ancestral populations, which database stewards offer adequate samples, and additional facilitators for use of diverse ancestral data.

Design, setting, and participants: This survey study was conducted from June to December 2022 and was part of an exploratory sequential mixed-methods project in which previous qualitative results informed survey design. Eligible participants included genetic researchers who held US academic affiliations and conducted research using human …

Antitumor Efficacy And Safety Of Unedited Autologous Cd5car T Cells In Relapsed/Refractory Mature T-Cell Lymphomas, Laquisa C Hill, Rayne H Rouce, Mengfen J Wu, Tao Wang, Royce Ma, Huimin Zhang, Birju Mehta, Natalia Lapteva, Zhuyong Mei, Tyler S Smith, Lina Yang, Madhuwanti Srinivasan, Phillip M Burkhardt, Carlos A Ramos, Premal Lulla, Martha Arredondo, Bambi Grilley, Helen E Heslop, Malcolm K Brenner, Maksim Mamonkin

Center for Medical Ethics and Health Policy Staff Publications

Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires additional gene modifications to overcome fratricide because of shared T-cell antigens on normal and malignant T cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels in transduced T cells while retaining strong cytotoxicity against CD5⁺ malignant cells. In our first-in-human phase 1 study (NCT0308190), second-generation autologous CD5.CAR T cells were manufactured from patients with r/r T-cell malignancies. Here, we report safety …

Investigating The Roles And Responsibilities Of Institutional Signing Officials After Data Sharing Policy Reform For Federally Funded Research In The United States: National Survey, Jinyoung Baek, Jonathan Lawson, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Background: New federal policies along with rapid growth in data generation, storage, and analysis tools are together driving scientific data sharing in the United States. At the same, triangulating human research data from diverse sources can also create situations where data are used for future research in ways that individuals and communities may consider objectionable. Institutional gatekeepers, namely, signing officials (SOs), are therefore at the helm of compliant management and sharing of human data for research. Of those with data governance responsibilities, SOs most often serve as signatories for investigators who deposit, access, and share research data between institutions. Although …

Environmental Detection Of Parasites In The Marginalized Paiute Reservations Compared To A Nearby Area, Shannon Mckim, Kristen Kopystynsky, Nathaniel Wolf, Fahim A Akbar, Maria Elena Bottazzi, Peter J Hotez, Rojelio Mejia

Center for Medical Ethics and Health Policy Staff Publications

The amounts of parasite DNA in soil samples from different playgrounds and other public areas can help identify areas of possible microbe transmission and give indications of the possible occurrence of parasite infection in nearby communities. We collected 207 soil samples from parks in Paiute indigenous tribal areas in southwestern Utah and from the higher income city of St. George, Utah, and tested them for 11 parasites that can cause human disease. Molecular tests revealed an elevated odds ratio (OR) of 3.072 (range, 1.114-8.065) for detecting the helminth Trichuris trichiura and an elevated OR of 3.036 (range, 1.101-7.966) for any …

Rational Prescribing Of Pancreatic Enzymes For Patients With Pancreatic Cancer, Mary Acelle G Garcia, Syed Imam, Ursula K Braun, Leanne K Jackson

Center for Medical Ethics and Health Policy Staff Publications

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy (PERT). Its effectiveness is also highly dependent on its proper timing of administration, and patients must be thoroughly educated about this. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use …

A Systematic Review Of Naldemedine And Naloxegol For The Treatment Of Opioid-Induced Constipation In Cancer Patients, Ursula K Braun, Leanne K Jackson, Mary A Garcia, Syed N Imam

Center for Medical Ethics and Health Policy Staff Publications

Background: Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients.

Objective: to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients.

Methods: a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients.

Results: Only three prospective randomized, double-blind, placebo-controlled clinical trials for …

Self-Sampling For Human Papillomavirus Testing: Acceptability In A Us Safety Net Health System, Susan L Parker, Trisha L Amboree, Shaun Bulsara, Maria Daheri, Matthew L Anderson, Susan G Hilsenbeck, Maria L Jibaja-Weiss, Mohammed Zare, Kathleen M Schmeler, Ashish A Deshmukh, Elizabeth Y Chiao, Michael E Scheurer, Jane R Montealegre

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system.

Methods: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to …

Building Effective Mentoring Relationships During Clinical Ethics Fellowships: Pedagogy, Programs, And People, Trevor M Bibler, Ryan H Nelson, Bryanna Moore, Janet Malek, Mary A Majumder

Center for Medical Ethics and Health Policy Staff Publications

How should clinical ethicists be trained? Scholars have stated that clinical ethics fellowships create well-trained, competent ethicists. While this appears intuitive, few features of fellowship programs have been publicly discussed, let alone debated. In this paper, we examine how fellowships can foster effective mentoring relationships. These relationships provide the foundation for the fellow's transition from novice to competent professional. In this essay, we begin by discussing our pedagogical commitments. Next, we describe the structures our program has created to assist our fellows in becoming competent ethicists. We then outline the kinds of knowledge, skills, and professional attributes mentors should possess. …

Igg In The Trenches: Results Of An In-Depth Interview Study On The Practice, Politics, And Future Of Investigative Genetic Genealogy, Christi J Guerrini, Whitney Bash Brooks, Jill O Robinson, Stephanie M Fullerton, Emily Zoorob, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Investigative genetic genealogy (IGG) is a new technique for identifying criminal suspects and unidentified deceased and living persons that has sparked controversy. In a criminal case, the technique involves uploading genetic information left by a putative perpetrator at the crime scene to one or more direct-to-consumer genetic genealogy databases with the intention of identifying the perpetrator's genetic relatives and, eventually, locating the perpetrator on the family tree. In 2018, IGG helped to identify the Golden State Killer, and it has since been used in hundreds of investigations in the United States. Here, we report findings from in-depth interviews with 24 …

Pretesting Discrete-Choice Experiments: A Guide For Researchers, Nicola B Campoamor, Christi J Guerrini, Whitney Bash Brooks, John F P Bridges, Norah L Crossnohere

Center for Medical Ethics and Health Policy Staff Publications

Discrete-choice experiments (DCEs) are a frequently used method to explore the preferences of patients and other decision-makers in health. Pretesting is an essential stage in the design of a high-quality choice experiment and involves engaging with representatives of the target population to improve the readability, presentation, and structure of the preference instrument. The goal of pretesting in DCEs is to improve the validity, reliability, and relevance of the survey, while decreasing sources of bias, burden, and error associated with preference elicitation, data collection, and interpretation of the data. Despite its value to inform DCE design, pretesting lacks documented good practices …

Case Sampling For Evaluating Hospital Postoperative Morbidity In Us Surgical Quality Improvement Programs, Vivi W Chen, Tracey Rosen, Yongquan Dong, Peter A Richardson, Jennifer R Kramer, Laura A Petersen, Nader N Massarweh

Center for Medical Ethics and Health Policy Staff Publications

Importance: US surgical quality improvement (QI) programs use data from a systematic sample of surgical cases, rather than universal review of all cases, to assess and compare risk-adjusted hospital postoperative complication rates. Given decreasing postoperative complication rates over time and the types of cases eligible for abstraction, it is unclear whether case sampling is robust for identifying hospitals with higher than expected complications.

Objective: To compare the assessment of hospital 30-day complication rates derived from sampling strategy used by some US surgical QI programs relative to universal review of all cases.

Design, setting, and participants: This US hospital-level analysis took …

A Phase 1 Trial Utilizing A Pharmacokinetic Endpoint To Determine The Optimal Dose Of Ramucirumab In Children And Adolescents With Relapsed Or Refractory Solid Tumors, Including Central Nervous System Tumors, Kristy L Pilbeam, Kamnesh Pradhan, James Croop, Charles G Minard, Xiaowei Liu, Stephan D Voss, Emasenyie Isikwei, Stacey L Berg, Joel M Reid, Elizabeth Fox, Brenda J Weigel

Center for Medical Ethics and Health Policy Staff Publications

Background: Ramucirumab is a monoclonal antibody that binds the extracellular domain of vascular endothelial growth factor receptor (VEGFR-2) and prevents binding of VEGF ligands. Based on population pharmacokinetic (PK) analysis and correlation with efficacy in adults, a target steady state trough concentration (Css,min ) ≥ 50 µg/mL was established.

Procedures: This phase 1 trial (ADVL1416) used a rolling six design and a PK primary endpoint to define the recommended phase 2 dose (RP2D) of ramucirumab in children with recurrent/refractory solid tumors. Two dose levels (DL) were planned (DL1: 8 mg/kg, DL2: 12 mg/kg administered intravenously [IV] every 2 weeks). Toxicity …

Parental Descriptions Of Childhood Avoidance Symptoms After Trauma, Zoe Blair-Andrews, Alison Salloum, Stephanie Evans, Vicky Phares, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Recognizing and diagnosing the avoidance symptom cluster of posttraumatic stress disorder (PTSD) in young children has been challenging. This study examines caregivers' descriptions of young children's avoidance reactions. By describing parents' examples of childhood avoidance, clinicians, researchers, and educators may be able to provide more specific psychoeducation which may improve identification of avoidance behaviors in young children. Caregivers (N=73) of young children (age 3-7 years) participated in a semi-structured diagnostic clinical interview prior to enrolling in a clinical trial for childhood trauma. The assessment regarding the caregiver's description of the child's avoidance was audio recorded and transcribed for a thematic …

Evidence Review And Considerations For Use Of First Line Genome Sequencing To Diagnose Rare Genetic Disorders, Kristen M Wigby, Deanna Brockman, Gregory Costain, Caitlin Hale, Stacie L Taylor, John Belmont, David Bick, David Dimmock, Susan Fernbach, John Greally, Vaidehi Jobanputra, Shashikant Kulkarni, Elizabeth Spiteri, Ryan J Taft

Center for Medical Ethics and Health Policy Staff Publications

Early use of genome sequencing (GS) in the diagnostic odyssey can reduce suffering and improve care, but questions remain about which patient populations are most amenable to GS as a first-line diagnostic test. To address this, the Medical Genome Initiative conducted a literature review to identify appropriate clinical indications for GS. Studies published from January 2011 to August 2022 that reported on the diagnostic yield (DY) or clinical utility of GS were included. An exploratory meta-analysis using a random effects model evaluated DY based on cohort size and diagnosed cases per cohort. Seventy-one studies met inclusion criteria, comprising over 13,000 …

A Review Of Olanzapine In The Treatment Of Cancer Anorexia-Cachexia Syndrome, Ivy O Poon, Veronica Ajewole, Ursula K Braun

Center for Medical Ethics and Health Policy Staff Publications

Background: Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS.

Methods: A …