Health Policy Commons^™

Incidence And 5-Year Survival Of Children And Adolescents With Hepatoblastoma In The United States, Justin A Kahla, David A Siegel, Shifan Dai, Philip J Lupo, Jennifer H Foster, Michael E Scheurer, Andras A Heczey

Center for Medical Ethics and Health Policy Staff Publications

Objective: Hepatoblastoma (HB) is the most common pediatric primary malignant liver tumor, its incidence has been increasing worldwide, but recent changes in incidence and outcomes with high population coverage are not well characterized.

Methods: We defined the incidence of HB diagnosed during 2003-2017 from United States Cancer Statistics (USCS) database, and survival during 2001-2016 from the National Program of Cancer Registries (NPCR). Data were stratified by sex, race/ethnicity, age, tumor stage, county population, and diagnosis year. Incidence trends were assessed by calculating average annual percent change (AAPC) using Joinpoint regression. Differences in overall 5-year survival were estimated using Cox regression …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …

Psychiatric Polygenic Risk Scores: Child And Adolescent Psychiatrists’ Knowledge, Attitudes, And Experiences, Stacey Pereira, Katrina A Muñoz, Brent J Small, Takahiro Soda, Laura N Torgerson, Clarissa E Sanchez, Jehannine Austin, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Psychiatric polygenic risk scores (PRS) have potential utility in psychiatric care and prevention, but there are concerns about their implementation. We surveyed 960 US-based practicing child and adolescent psychiatrists' (CAP) about their experiences, perspectives, and potential uses of psychiatric PRS. While 23% of CAP reported that they had never heard of PRS, 10 % of respondents have had a patient/family bring PRS to them and 4% have generated PRS for patients. Though 25% stated they would request PRS if a patient/caregiver asked, 35% indicated that nothing would prompt them to request PRS. Most respondents (54%) believed psychiatric PRS are currently …

T1 Signal Intensity Ratio Of The Pancreas As An Imaging Biomarker For The Staging Of Chronic Pancreatitis, Temel Tirkes, Anil K Dasyam, Zarine K Shah, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Stephanie T Chang, Carlos A Farinas, Joseph R Grajo, Kareem Mawad, Naoki Takahashi, Sudhakar K Venkatesh, Ashley Wachsman, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Stephen K Van Den Eeden, Yunlong Yang, Mark Topazian, Dana K Andersen, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study.

Methods: The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their …

Residence In A Latinx Enclave And End-Induction Minimal Residual Disease Positivity Among Children With Acute Lymphoblastic Leukemia, Joshua P Muñiz, John P Woodhouse, Amy E Hughes, Sandi L Pruitt, Karen R Rabin, Michael E Scheurer, Philip J Lupo, Jeremy M Schraw

Center for Medical Ethics and Health Policy Staff Publications

Racial and ethnic inequities in survival persist for children with acute lymphoblastic leukemia (ALL). In the US, there are strong associations between SES, race/ethnicity, and place of residence. This is evidenced by ethnic enclaves: neighborhoods with high concentrations of ethnic residents, immigrants, and language isolation. The Latinx enclave index (LEI) can be used to investigate how residence in a Latinx enclave is associated with health outcomes. We studied the association between LEI score and minimal residual disease (MRD) in 142 pediatric ALL patients treated at Texas Children's Hospital. LEI score was associated with end-induction MRD positivity (OR per unit increase …

Characteristics Of Graft-Versus-Host Disease (Gvhd) After Post-Transplantation Cyclophosphamide Versus Conventional Gvhd Prophylaxis, Rima M Saliba, Amin M Alousi, Joseph Pidala, Mukta Arora, Stephen R Spellman, Michael T Hemmer, Tao Wang, Camille Abboud, Sairah Ahmed, Joseph H Antin, Amer Beitinjaneh, David Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choe, Rabi Hanna, Peiman Hematti, Rammurti T Kamble, Carrie L Kitko, Mary Laughlin, Lazaros Lekakis, Margaret L Macmillan, Rodrigo Martino, Parinda A Mehta, Taiga Nishihori, Sagar S Patel, Miguel-Angel Perales, Hemalatha G Rangarajan, Olov Ringdén, Joseph Rosenthal, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Takanori Teshima, Marjolein Van Der Poel, Leo F Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A Yared, Jeffrey Schriber, Richard E Champlin, Stefan O Ciurea

Center for Medical Ethics and Health Policy Staff Publications

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin …

Towards A Definitive Symptom Structure Of Obsessive-Compulsive Disorder: A Factor And Network Analysis Of 87 Distinct Symptoms In 1366 Individuals, Matti Cervin, Euripedes C Miguel, Ayşegül Selcen Güler, Ygor A Ferrão, Ayşe Burcu Erdoğdu, Luisa Lazaro, Sebla Gökçe, Daniel A Geller, Yasemin Yulaf, Şaziye Senem Başgül, Özlem Özcan, Koray Karabekiroğlu, Leonardo F Fontenelle, Yankı Yazgan, Eric A Storch, James F Leckman, Maria Conceição Do Rosário, David Mataix-Cols

Center for Medical Ethics and Health Policy Staff Publications

Background: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques.

Methods: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the …

Longitudinal Investigation Of Suicidal Ideation And Associated Factors During Pediatric Acute Lymphoblastic Leukemia Chemotherapy, Kimberly P Raghubar, Tiffany Chambers, Ryan M Hill, Olga Taylor, Marilyn Hockenberry, M Casey Hooke, Pauline Mitby, Ida Ki Moore, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Objective: This study describes the prevalence of suicidal ideation (SI) during acute lymphoblastic leukemia (ALL) therapy and investigates the influence of clinical factors and physical symptoms on SI.

Methods: The Children's Depressive Inventory (CDI-2) was administered to ALL patients (diagnosed 2012-2017) at start of consolidation, delayed intensification (DI), maintenance cycle 1 (MC1), and maintenance cycle 2 (MC2) in a multi-site study. SI was present if patients endorsed the item "I want to kill myself." Logistic regression models evaluated associations between SI and sociodemographic factors; depressive symptoms; and below average, average, and above average symptom clusters identified using latent class analysis …

Covid-19 And Children, Carl A Pierce, Kevan C Herold, Betsy C Herold, Janet Chou, Adrienne Randolph, Binita Kane, Sammie Mcfarland, Deepti Gurdasani, Christina Pagel, Peter Hotez, Sarah Cobey, Scott E Hensley

Center for Medical Ethics and Health Policy Staff Publications

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in …

Leveraging Clinical Trial Populations And Data From The Children's Oncology Group For Cancer Survivorship Research, Eric J Chow, Lena E Winestone, Philip J Lupo, Lisa R Diller, Tara O Henderson, Nina S Kadan-Lottick, Jennifer M Levine, Kirsten K Ness, Smita Bhatia, Saro H Armenian

Center for Medical Ethics and Health Policy Staff Publications

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship …

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

Recommendations For Whole Genome Sequencing In Diagnostics For Rare Diseases, Erika Souche, Sergi Beltran, Erwin Brosens, John W Belmont, Magdalena Fossum, Olaf Riess, Christian Gilissen, Amin Ardeshirdavani, Gunnar Houge, Marielle Van Gijn, Jill Clayton-Smith, Matthis Synofzik, Nicole De Leeuw, Zandra C Deans, Yasemin Dincer, Sebastian H Eck, Saskia Van Der Crabben, Meena Balasubramanian, Holm Graessner, Marc Sturm, Helen Firth, Alessandra Ferlini, Rima Nabbout, Elfride De Baere, Thomas Liehr, Milan Macek, Gert Matthijs, Hans Scheffer, Peter Bauer, Helger G Yntema, Marjan M Weiss

Center for Medical Ethics and Health Policy Staff Publications

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions. The use of WGS in diagnostics warrants the re-evaluation …

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

Center for Medical Ethics and Health Policy Staff Publications

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

Change During Cognitive And Exposure Phases Of Cognitive-Behavioral Therapy For Autistic Youth With Anxiety Disorders, Andrew G Guzick, Sophie C Schneider, Philip C Kendall, Jeffrey J Wood, Connor M Kerns, Brent J Small, Ye Eun Park, Sandra L Cepeda, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Objective: To evaluate improvement during the (a) cognitive and (b) exposure therapy phases of cognitive-behavioral therapy (CBT) for autistic youth with anxiety disorders.

Method: Participants were 148 autistic youth (aged 7-13; 77% male; 64% White) with clinically significant anxiety who were randomized to standard or adapted CBT. Clinician-rated anxiety severity was recorded at each appointment. Trajectories of change during (a) the cognitive phase and (b) the exposure phase of treatment were analyzed using piecewise multilevel modeling.

Results: Compared to the psychoeducation and cognitive therapy phases, the exposure phase corresponded with significantly more rapid symptom reduction, b = -.11, 95% CI …

High Prevalence Of Osteopathy In Chronic Pancreatitis: A Cross-Sectional Analysis From The Proceed Study, Phil A Hart, Dhiraj Yadav, Liang Li, Savi Appana, William Fisher, Evan Fogel, Chris E Forsmark, Walter G Park, Stephen Pandol, Mark D Topazian, Stephen K Van Den Eden, Santhi Swaroop Vege, David Bradley, Jose Serrano, Darwin L Conwell

Center for Medical Ethics and Health Policy Staff Publications

Background & aims: Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.

Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression …

Vaccine-Linked Chemotherapy With A Low Dose Of Benznidazole Plus A Bivalent Recombinant Protein Vaccine Prevents The Development Of Cardiac Fibrosis Caused By Trypanosoma Cruzi In Chronically-Infected Balb/C Mice, Victor Manuel Dzul-Huchim, Maria Jesus Ramirez-Sierra, Pedro Pablo Martinez-Vega, Miguel Enrique Rosado-Vallado, Victor Ermilo Arana-Argaez, Jaime Ortega-Lopez, Fabian Gusovsky, Eric Dumonteil, Julio Vladimir Cruz-Chan, Peter Hotez, María Elena Bottazzi, Liliana Estefania Villanueva-Lizama

Center for Medical Ethics and Health Policy Staff Publications

Background: Chagas disease (CD) is caused by Trypanosoma cruzi and affects 6-7 million people worldwide. Approximately 30% of chronic patients develop chronic chagasic cardiomyopathy (CCC) after decades. Benznidazole (BNZ), one of the first-line chemotherapy used for CD, induces toxicity and fails to halt the progression of CCC in chronic patients. The recombinant parasite-derived antigens, including Tc24, Tc24-C4, TSA-1, and TSA-1-C4 with Toll-like receptor 4 (TLR-4) agonist-adjuvants reduce cardiac parasite burdens, heart inflammation, and fibrosis, leading us to envision their use as immunotherapy together with BNZ. Given genetic immunization (DNA vaccines) encoding Tc24 and TSA-1 induce protective immunity in mice and …

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

Results: We estimated roughly 9.7 million YLLs due …

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

Center for Medical Ethics and Health Policy Staff Publications

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

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

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 …

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 …

De Novo Heterozygous Variants In Slc30a7 Are A Candidate Cause For Joubert Syndrome, Monica Penon-Portmann, Mohammad K Eldomery, Lorraine Potocki, Dana Marafi, Jennifer E Posey, Zeynep Coban-Akdemir, Tamar Harel, Christopher M Grochowski, Hailey Loucks, Walter Patrick Devine, Jessica Van Ziffle, Dan Doherty, James R Lupski, Joseph T Shieh

Center for Medical Ethics and Health Policy Staff Publications

Joubert syndrome (JS), a well-established ciliopathy, is characterized by the distinctive molar tooth sign on brain MRI, ataxia, and neurodevelopmental features. Other manifestations can include polydactyly, accessory frenula, renal, or liver disease. Here, we report individuals meeting criteria for JS with de novo heterozygous variants in SLC30A7 (Chr1p21.2). The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. Exome sequencing detected a de novo heterozygous missense variant in SLC30A7: NM_133496.5: c.407 T > C, (p.Val136Ala). The second individual had bilateral postaxial polydactyly, molar …

Circulating Trophoblast Numbers As A Potential Marker For Pregnancy Complications, Brielle Crovetti, Mohamad Ali Maktabi, Hadi Erfani, Tachjaree Panchalee, Qun Wang, Liesbeth Vossaert, Ignatia Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Objective: To explore the potential of circulating trophoblasts (TBs) as a non-invasive tool to assess placental health and predict obstetric complications.

Methods: We retrospectively reviewed maternal characteristics and pregnancy outcomes of 369 women who enrolled in our original cell-based NIPT (cbNIPT) study. The number of circulating TBs recovered from the maternal blood samples was recorded and expressed as fetal cell concentration (FCC). We evaluated if FCC can be used to predict pregnancy outcomes such as hypertensive disorders of pregnancy (HDP), fetal growth restriction, placental abruption, preterm labor, and pregnancy loss.

Results: Receiver operating characteristic (ROC) analysis was performed to find …

Stepped Care Versus Standard Care For Children After Trauma: A Randomized Non-Inferiority Clinical Trial, Alison Salloum, Yuanyuan Lu, Henian Chen, Troy Quast, Judith A Cohen, Michael S Scheeringa, Kristen Salomon, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Objective: Trauma-focused cognitive-behavioral therapy (TF-CBT) is an evidence-based therapist-led treatment for children after trauma. Parents often experience barriers to treatment engagement, including cost. Stepped care TF-CBT (SC-TF-CBT) was developed as an alternative delivery system. Step One is a parent-led therapist-assisted treatment. Step Two provides therapist-led TF-CBT for children who did not benefit from Step One and require more intensive treatment. This study compared SC-TF-CBT to standard TF-CBT in a community-based non-inferiority trial.

Method: A total of 183 children (aged 4-12 years) experiencing posttraumatic stress symptoms (PTSS) and their caregivers were randomly assigned to SC-TF-CBT or standard TF-CBT within 6 community …

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 …

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 …

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 …