Medicine and Health Sciences Commons^™

Impulsivity Facets And Substance Use Involvement: Insights From Genomic Structural Equation Modeling, Laura Vilar-Ribó, Alexander S Hatoum, Andrew D Grotzinger, Travis T Mallard, 23andme Research Team, Sarah Elson, Pierre Fontanillas, Abraham A Palmer, Daniel E Gustavson, Sandra Sanchez-Roige

2020-Current year OA Pubs

BACKGROUND: Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear.

METHODS: We used genomic structural equation modeling and genome-wide association studies (

RESULTS: We found that the SU and SUD factors were strongly genetically inter-correlated (

CONCLUSIONS: Our findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.

Contribution Of Rare Chromosome 22q112 Copy Number Variants To Non-Syndromic Bicuspid Aortic Valve, Helene Digregorio, Sara Mansoorshahi, Steven G Carlisle, Catherina Tovar Pensa, Abi Watts, Courtney Mcneely, Anna Sabate-Rotes, Anji Yetman, Hector I Michelena, Julie F A De Backer, Laura Muiño Mosquera, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Simon C Body, Dianna M Milewicz, Siddharth K Prakash, Ebav Investigators

Faculty, Staff and Student Publications

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications.

Methods: Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset …

Assessing Dynamic Cognitive Function In The Daily Lives Of Youths With And Without Type 1 Diabetes: Usability Study, Mary Katherine Ray, Jorie Fleming, Andrew Aschenbrenner, Jason Hassenstab, Brooke Redwine, Carissa Burns, Ana Maria Arbelaez, Mary Ellen Vajravelu, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Studies have shown a relationship between worse glycemic control and lower cognitive scores in youths with type 1 diabetes (T1D). However, most studies assess long-term glucose control (eg, years-decades) and cognition at a single time point. Understanding this relationship at a higher temporal resolution (eg, minutes-hours) and in naturalistic settings has potential clinical implications. Newer technology (eg, continuous glucose monitoring [CGM] and ecological momentary assessment) provides a unique opportunity to explore the glucose dynamics that influence dynamic cognition; that is, cognitive functions that fluctuate short-term and are influenced by environmental factors.

OBJECTIVE: Before we can assess this relationship, we …

Utility Of Caregiver Signaling Questions To Detect Neurocognitive Impairment In Children With Sickle Cell Disease, Christina M Dandar, Lakia Kearson, Jennifer N Longoria, Brian Potter, Allison A King, Jeffrey Gossett, Clifford M Takemoto, Jane S Hankins, Guolian Kang, Andrew M Heitzer

2020-Current year OA Pubs

The American Society of Hematology cerebrovascular guidelines for sickle cell disease (SCD) recommend surveillance using signaling questions to screen for neurocognitive difficulties, although the clinical utility of these signaling questions has yet to be established. This study aimed to determine the clinical utility of caregiver signaling questions for detecting significant neurocognitive impairment (defined as >1.5 standard deviation [SD] below the normative mean on ≥2 measures) and domain-specific impairment (defined as >1.5 SD below the normative mean) in children and adolescents with SCD. A total of 421 caregivers of children with SCD aged 8 to 17 years (62% hemoglobin SS (HbSS) …

A Rare Case Of Adolescent Epiglottitis Secondary To Streptococcus Dysgalactiae Septicemia., Kedar Tilak, Mohamed Aashiq Abdul Ghayum, Douglas Swanson, Rana El Feghaly

Manuscripts, Articles, Book Chapters and Other Papers

Streptococcus dysgalactiae (S. dysgalactiae)is a relatively uncommon pathogen in the pediatric populations, often overshadowed by Streptococcus pyogenes (S. pyogenes)in causing diseases such as cellulitis, severe seep tissue necrotizing infections, and streptococcal toxic shock syndrome. This case report presents the case of a 15-year-old recent immigrant male patient from Egypt who developed an extensive neck infection with complications from S. dysgalactiae septicemia. Initially misdiagnosed as viral pharyngitis, the patient was later admitted with high fevers, dysphagia, and progressive respiratory distress. Imaging revealed widespread inflammatory changes, including cellulitis, epiglottitis, and lymphadenopathy. Despite prompt antibiotic therapy, the patient required …

Dna-Binding Affinity And Specificity Determine The Phenotypic Diversity In Bcl11b-Related Disorders, Ivana Lessel, Anja Baresic, Ivan K Chinn, Jonathan May, Anu Goenka, Kate E Chandler, Jennifer E Posey, Alexandra Afenjar, Luisa Averdunk, Maria Francesca Bedeschi, Thomas Besnard, Rae Brager, Lauren Brick, Melanie Brugger, Theresa Brunet, Susan Byrne, Oscar De La Calle-Martín, Valeria Capra, Paul Cardenas, Céline Chappé, Hey J Chong, Benjamin Cogne, Erin Conboy, Heidi Cope, Thomas Courtin, Wallid Deb, Robertino Dilena, Christèle Dubourg, Magdeldin Elgizouli, Erica Fernandes, Kristi K Fitzgerald, Silvana Gangi, Jaya K George-Abraham, Muge Gucsavas-Calikoglu, Tobias B Haack, Medard Hadonou, Britta Hanker, Irina Hüning, Maria Iascone, Bertrand Isidor, Irma Järvelä, Jay J Jin, Alexander A L Jorge, Dragana Josifova, Ruta Kalinauskiene, Erik-Jan Kamsteeg, Boris Keren, Elena Kessler, Heike Kölbel, Mariya Kozenko, Christian Kubisch, Alma Kuechler, Suzanne M Leal, Juha Leppälä, Sharon M Luu, Gholson J Lyon, Suneeta Madan-Khetarpal, Margherita Mancardi, Elaine Marchi, Lakshmi Mehta, Beatriz Menendez, Chantal F Morel, Sue Moyer Harasink, Dayna-Lynn Nevay, Vincenzo Nigro, Sylvie Odent, Renske Oegema, John Pappas, Matthew T Pastore, Yezmin Perilla-Young, Konrad Platzer, Nina Powell-Hamilton, Rachel Rabin, Aisha Rekab, Raissa C Rezende, Leema Robert, Ferruccio Romano, Marcello Scala, Karin Poths, Isabelle Schrauwen, Jessica Sebastian, John Short, Richard Sidlow, Jennifer Sullivan, Katalin Szakszon, Queenie K G Tan, Undiagnosed Diseases Network, Matias Wagner, Dagmar Wieczorek, Bo Yuan, Nicole Maeding, Dirk Strunk, Amber Begtrup, Siddharth Banka, James R Lupski, Eva Tolosa, Davor Lessel

Faculty, Staff and Students Publications

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. …

Immunogenicity And Reactogenicity Of High- Or Standard-Dose Influenza Vaccine In A Second Consecutive Influenza Season., Hannah Bahakel, Andrew J. Spieker, Haya Hayek, Jennifer E. Schuster, Lubna Hamdan, Daniel E. Dulek, Carrie L. Kitko, Tess Stopczynski, Einas Batarseh, Zaid Haddadin, Laura S. Stewart, Anna Stahl, Molly Potter, Herdi Rahman, Justin Amarin, Spyros A. Kalams, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Christopher J. Harrison, Jason Freedman, Paul A. Carpenter, Janet A. Englund, Flor M. Munoz, Lara Danziger-Isakov, Natasha Halasa, Pediatric Hct Flu Study

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatric hematopoietic cell transplant (HCT) recipients are at high risk for morbidity from influenza virus infection. We demonstrated in a primary phase 2 randomized controlled trial that 2 post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given 4 weeks apart were more immunogenic than 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present the immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen.

METHODS: A subcohort of study participants reenrolled and had hemagglutinin inhibition titers measured at baseline and 4 weeks after each vaccine dose in year 2. We estimated …

Metabolites And Lipid Species Mediate The Associations Of Adiposity In Childhood And Early Adulthood With Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Lili Liu, Lei Liu, Haixiang Zhang, Chongliang Luo, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women.

METHODS: This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. …

Combined Clinical, Structural And Cellular Studies Discriminate Pathogenic And Benign Trpv4 Variants, Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karam, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A Mccray

Faculty, Staff and Students Publications

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 …

School-Based Protective Factors For Hiv Prevention In The United States: Secondary Analysis Of The Youth Risk Behavior Survey 2015-2019, David R. Garcia, Jason Fletcher, Lloyd Goldsamt, David L. Bell, Yaguang Zheng, Ann-Margaret Dunn Navarra

School of Nursing Faculty Publications

This secondary analysis of the National Youth Risk Behavior Survey (years 2015-2019) examines associations between school-based protective factors (i.e., safe school environments and academic achievement) and HIV risk behaviors among sexually experienced adolescent gay and bisexual men ( n = 644), a population with the highest prevalence of undiagnosed HIV infections. Demographics included Hispanics/Latinos (25%, n = 158), Other race/ethnicity (14%, n = 88), and non-Hispanic Blacks/African Americans (13%, n = 81). Adjusted models showed that protective factors reduced odds for early sexual debut, multiple sexual partners, sex under the influence of drugs/alcohol, and condomless sex, with an additive effect …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off-target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage by …

Emapalumab Treatment In Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis In The United States: A Retrospective Medical Chart Review Study, Shanmuganathan Chandrakasan, Carl E Allen, Deepika Bhatla, John Carter, May Chien, Robert Cooper, Lauren Draper, Olive S Eckstein, Rabi Hanna, J Allyson Hays, Michelle L Hermiston, Ashley P Hinson, Patricia M Hobday, Michael S Isakoff, Michael B Jordan, Jennifer W Leiding, Renee Modica, Taizo A Nakano, Abiola Oladapo, Sachit A Patel, Priti Pednekar, Mona Riskalla, Susmita N Sarangi, Prakash Satwani, Anand Tandra, Kelly J Walkovich, John D Yee, Adi Zoref-Lorenz, Edward M Behrens

Faculty, Staff and Students Publications

Objective: Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.

Methods: REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.

Results: Fifteen of 105 patients …

Effectiveness Of The Primary Bacillus Calmette-Guérin Vaccine Against The Risk Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease: A Meta-Analysis Of Individual Participant Data, Puck T Pelzer, Logan Stuck, Leonardo Martinez, Alexandra S Richards, Carlos Acuña-Villaorduña, Naomi E Aronson, Maryline Bonnet, Anna C Carvalho, Pei-Chun Chan, Li-Min Huang, Chi-Tai Fang, Gavin Churchyard, Helena Del Corral-Londoño, Manjula Datta, Marcos A Espinal, Katherine Fielding, Andrew J Fiore-Gartland, Alberto Garcia-Basteiro, Willem Hanekom, Mark Hatherill, Phillip C Hill, Helena Huerga, Edward C Jones-López, Afranio Kritski, Anna M Mandalakas, Punam Mangtani, Eduardo Martins Netto, Harriet Mayanja, Rufaida Mazahir, Megan Murray, Molebogeng Rangaka, Thomas Scriba, Jitendra Singh, Sarman Singh, Catherine M Stein, Johan Vekemans, Lilly M Verhagen, Julian A Villalba, Anne Wajja, Basilea Watson, Richard G White, Frank G J Cobelens

Faculty, Staff and Students Publications

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

Methods: We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON …

Five-Year Outcomes Of Lenadogene Nolparvovec Gene Therapy In Leber Hereditary Optic Neuropathy, Patrick Yu-Wai-Man, Nancy Newman, Valérie Biousse, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo Sadun, Robert C Sergott, Rabih Hage, Simona Degli Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Magali Taiel, José-Alain Sahel

Department of Neurology Faculty Papers

IMPORTANCE: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

OBJECTIVE: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

DESIGN, SETTING, AND PARTICIPANTS: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE …

Prediction Models Of Basal Energy Expenditure In Children And Adolescents Across The Bmi Spectrum Based On Room Calorimetry: A Cross-Sectional Cohort Study, Maurice Puyau, Roman Shypailo, Nancy F Butte, Salma Musaad, Fida Bacha

Children’s Nutrition Research Center Staff Publications

Background: Existing equations for prediction of basal energy expenditure (BEE) may not be accurate in children with overweight or obesity (OW/OB).

Objectives: We aimed to develop BEE prediction equations applicable to children and adolescents across a wide BMI spectrum using gold standard room calorimetry.

Methods: We measured weight, height, waist and hip circumferences, body composition (DXA), and BEE (whole room calorimetry) in a cross-sectional cohort of 1155 healthy children, 5-19 years of age. 67% of the males and 51% of the females were classified as OW/OB. We applied multiple linear regression analyses to develop BEE prediction models for each sex. …

Identifying Mechanisms Of Action For Implementation Strategies Using A Retrospective Implementation Mapping Logic Model Approach, Timothy J Walker, Funlola Are, Natalia I Heredia, Kempson Onadeko, Emma E Saving, Eunyoung Kang, Maria E Fernandez

Faculty, Staff and Student Publications

Understanding causal mechanisms for implementation strategies is a priority for implementation and health promotion research. Logic models are helpful for understanding and illustrating mechanisms through which implementation strategies operate. Little guidance exists for developing logic models for existing implementation strategies. We demonstrate how to use Implementation Mapping (IM) in a retrospective manner to develop an IMap Logic Model for a social-emotional learning program implemented at Boys & Girls Clubs of Greater Houston (BGCGH). To inform logic model development, we used qualitative interview data (from implementers) and conversations with program organizers. To develop the logic model, we specified the most accessible …

Exploring Individual Differences In Amygdala-Mediated Memory Modulation, Martina K Hollearn, Joseph R Manns, Lou T Blanpain, Stephan B Hamann, Kelly Bijanki, Robert E Gross, Daniel L Drane, Justin M Campbell, Krista L Wahlstrom, Griffin F Light, Aydin Tasevac, Phillip Demarest, Peter Brunner, Jon T Willie, Cory S Inman

Faculty, Staff and Students Publications

Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without …

Comparing One Stage, Chromogenic Assay Results And Discrepancies With Bleeding Phenotype And Genetic Variants In Females With Hemophilia A, Lakshmi Srivaths, Joanna Larson, Sepideh Saroukhani, Mohammed Said, Deborah Brown, Nidra Rodriguez, Neethu Menon, Miguel Escobar

Faculty, Staff and Student Publications

Background: Increasing evidence in females with hemophilia A has shown significant bleeding symptoms. Accurate factor (F) VIII activity (FVIII:C) measurement is essential to assign correct diagnosis and severity. Assay discrepancies reported in male patients with hemophilia A are not well studied in females.

Objectives: Our research sought to assess the association of FVIII:C levels by one-stage versus chromogenic assays and the assay discrepancy with bleeding phenotype and genetic mutation in females with hemophilia A.

Methods: Data from 64 females with hemophilia A from our center were reviewed with center's institutional review board approval. Descriptive statistics, chi-squared, Fisher's exact, and Bland-Altman …

Association Between Early Immunosuppression Center Variability And One-Year Outcomes After Pediatric Liver Transplant., Vikram K. Raghu, Scott D. Rothenberger, James E. Squires, Elizabeth Eisenberg, Anna L. Peters, Jennifer Halma, Swati Antala, Irini D. Batsis, Ke-You Zhang, Amy G. Feldman, Daniel H. Leung, Steven J. Lobritto, John Bucuvalas, Simon P. Horslen, George V. Mazariegos, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

METHODS: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, …

National Prescribing Practices For Pediatric Dystonia Among Providers In The United States., Sarah Paige Davis, Natalie J. Kane, Haley E. Botteron, Rose N. Gelineau-Morel

Manuscripts, Articles, Book Chapters and Other Papers

While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes real-world prescribing practices for pediatric dystonia in the United States, evaluating prescription frequency, dosing, and the impact of comorbidities. Oracle electronic health record real-world data were queried from 2014 to 2019 for encounters of patients under age 18 with a dystonia diagnosis and available medication records. Information was extracted on prescriptions for dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and select benzodiazepines), dosing, and comorbid diagnoses of cerebral palsy (CP), epilepsy, or spasticity. A total of 4010 pediatric patients with …

Improvement On The Slopes: The Impact Of An Adaptive Snow Sports Program On Children And Young Adults With Disabilities., Stephanie M. Barton, Matthew J. Mclaughlin, Mark T. Fisher

Manuscripts, Articles, Book Chapters and Other Papers

PurposeThis retrospective cohort study sought to examine participant skill and functional progression in an adaptive snow sports program for children and young adults with disabilities.MethodsOne hundred twelve individuals, majority male, who participated in at least 2 adapted ski or snowboard sessions were evaluated by trained adaptive instructors. The primary outcome measure was standardized skill level ranging from 1-novice to 9-expert. Secondary outcome measures of cognitive, emotional, social, physical, and independence scores, were rated on a scale from 1-5, with 5 being the highest.ResultsThe median number of sessions per participant was 4 (range 2-65 sessions) and median participation duration was 2 …

Bills To Restrict Access To And Harm From Indoor Tanning Facilities In Us State Legislatures, 1992‒2023, David B Buller, Julia Berteletti, Carolyn Heckman, Kevin R J Schroth, Alan C Geller, Jerod L Stapleton, Irene Adjei, Anna Mitarotondo, Samantha R Guild, Jeffrey E Gershenwald, Robert Dellavalle, Sherry Pagoto

Faculty, Staff and Student Publications

Objectives. To describe progression, content, and stringency of state legislation regulating indoor tanning and association with state government political party leadership.

Methods. Trained research assistants used legal mapping methods to code legislative bills on indoor tanning introduced in US states, the District of Columbia, and Puerto Rico. We calculated composite scores on the stringency of age restrictions and of warnings, operator requirements, and enforcement. We evaluated associations of the political party of the legislative sponsor and legislature majority.

Results. Between 1992 and 2023, 184 bills were introduced in 49 of 50 states and DC (56 laws were enacted, and 126 …

Comprehensive Assessment Reveals Numerous Clinical And Neurophysiological Differences Between Mecp2-Allelic Disorders, Davut Pehlivan, Chengjun Huang, Holly K Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G Glaze, Charles S Layne, Leonardo Sahelijo, Huda Y Zoghbi, Matthew J Mcginley, Bernhard Suter

Faculty, Staff and Students Publications

OBJECTIVE: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

MATERIALS AND METHODS: We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart.

RESULTS: We identified numerous clinical and physiological …

Exploring Reciprocal Links Between Early Adolescent Coping And Internalizing Symptoms, Caitlyn Mytelka, Sarah C Narendorf, Elizabeth Baumler, Chiara Acquati, Jeff R Temple

Faculty, Staff and Student Publications

Introduction: The rising prevalence of depression and anxiety among adolescents is a public health concern. Early adolescence is a key developmental period to reduce risks for internalizing symptoms through primary prevention programs, yet additional research is needed on modifiable factors, such as coping skills, to target to mitigate risk factors. Therefore, we investigated the reciprocal link between coping style and internalizing symptoms among a racially/ethnically diverse sample of early adolescents (n = 1273) from 12 middle schools over 1 year.

Methods: We leveraged a longitudinal data set of a cluster, randomized trial of a preventive intervention from 12 middle schools …

Cultural Consensus Modeling To Identify Culturally Relevant Reasons For And Against Suicide Among Black Adolescents, Ryan M Hill, Danielle Busby, Jennifer L Brown, Eric Sumlin, Estefania Fernandez, Carla Sharp

Faculty, Staff and Student Publications

Introduction: The development of evidence-based treatments relies on accurate theoretical frameworks sensitive to the lived realities of the populations from which they are derived. Yet, the perspectives of Black youth are vastly underrepresented in extant theories of suicidal behavior. Cultural Consensus Modeling provides an evidence-based approach for developing a culturally informed understanding of suicide risk among Black youth.

Method: Participants were 50 Black adolescents (Mage = 16.20 years; 76.0% male) who completed Phase 1 of a Cultural Consensus Modeling study. Participants freely listed reasons for suicide and reasons for living among similar peer Black youth. Responses were synthesized and coded …

Obesity Predisposes Anthracycline-Treated Survivors Of Childhood And Adolescent Cancers To Subclinical Cardiac Dysfunction, Ian A George, Brianna Souder, Amy Berkman, David H Noyd, M Jay Campbell, Piers C A Barker, Michael Roth, Michelle A T Hildebrandt, Kevin C Oeffinger, Andrew W Mccrary, Andrew P Landstrom

Faculty, Staff and Student Publications

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards …

Incidence And Survival Of Children And Adolescents With Wilms Tumor, United States, 2001-2020, Andres F Espinoza, Ekene Onwuka, David A Siegel, Shifan Dai, Sanjeev A Vasudevan, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Background: Wilms tumor (WT) is the most common pediatric malignancy of the kidney. Past studies describing WT incidence and survival used surveillance data with < 30% of the US population. We evaluated differences in WT incidence and survival comparing demographic groups and tumor characteristics.

Methods: We analyzed new cases of WT among patients aged < 20 years at diagnosis by using incidence data from US Cancer Statistics (USCS) for 2003-2020 and 5-year relative survival (RS) data from the National Program of Cancer Registries (NPCR) for 2001-2019. To assess incidence trends, average annual percent change (AAPC) was calculated by using joinpoint regression. Relative survival (RS) and all-cause survival were calculated overall and by demographic and clinical variables.

Results: During 2003-2020, 8218 cases of WT were reported in USCS, which represented an age-adjusted incidence rate of 5.7 cases per million. Rates were the highest among females (6.3), children aged 0-4 years (17.2), and non-Hispanic Black patients (7.1). Overall, trends remained stable (AAPC = -0.4, 95% CI: -1.4 to 0.4). Among 7567 cases of WT in NPCR, 5-year RS was 92.6%. Patients with the lowest …

Antiseizure Medication Prescribing In People With Dravet Syndrome: An Analysis Of Real-Time Administrative Data, Kevin Y Xu, Binx Yezhe Lin, M Scott Perry, Fábio A Nascimento

2020-Current year OA Pubs

Since 2018, three new antiseizure medications (ASMs) received FDA approval for Dravet syndrome (DS) in the U.S: cannabidiol, stiripentol, and fenfluramine. Yet, the uptake of these ASMs in routine clinical practice is unknown. We use new ICD-10 codes for DS (implemented in 2020) to estimate ASM receipt in patients with DS. We analyzed the TriNetX Network, a real-time electronic health record-based dataset linked to prescription data encompassing all 50 states of the U.S. After identifying patients with health care encounters for DS in 2021 and 2022 (via ICD-10 codes), we examined ASM prescribing in the year following a DS claim: …

Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers, Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Methods: Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The Gene …

Prospective Observational Study Of Fkrp-Related Limb-Girdle Muscular Dystrophy R9: A Grasp Consortium Study, Lindsay N Alfano, Stephanie Hunn, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving …