Digital Commons Network^™

Predicting Pediatric Tuberculosis: The Need For Age-Specific Host Biosignatures, Sara Suliman, Devan Jaganath, Andrew Dinardo

Faculty, Staff and Students Publications

No abstract provided.

Donor-Recipient Specificity And Age-Dependency In Fecal Microbiota Therapy And Probiotic Resolution Of Gastrointestinal Symptoms, Qinglong Wu, Prapaporn Boonma, Shyam Badu, Nazli Yalcinkaya, Sik Yu So, Kevin W Garey, Kent Williams, L Eugene Arnold, Robert J Shulman, Richard Kellermayer, Tor C Savidge

Faculty, Staff and Students Publications

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal …

Infants Admitted To Us Intensive Care Units For Rsv Infection During The 2022 Seasonal Peak., Natasha Halasa, Laura D. Zambrano, Justin Z. Amarin, Laura S. Stewart, Margaret M. Newhams, Emily R. Levy, Steven L. Shein, Christopher L. Carroll, Julie C. Fitzgerald, Marian G. Michaels, Katherine Bline, Melissa L. Cullimore, Laura Loftis, Vicki L. Montgomery, Asumthia S. Jeyapalan, Pia S. Pannaraj, Adam J. Schwarz, Natalie Z. Cvijanovich, Matt S. Zinter, Aline B. Maddux, Melania M. Bembea, Katherine Irby, Danielle M. Zerr, Joseph D. Kuebler, Christopher J. Babbitt, Mary Glas Gaspers, Ryan A. Nofziger, Michele Kong, Bria M. Coates, Jennifer E. Schuster, Shira J. Gertz, Elizabeth H. Mack, Benjamin R. White, Helen Harvey, Charlotte V. Hobbs, Heda Dapul, Andrew D. Butler, Tamara T. Bradford, Courtney M. Rowan, Kari Wellnitz, Mary Allen Staat, Cassyanne L. Aguiar, Saul R. Hymes, Adrienne G. Randolph, Angela P. Campbell, Rsv-Pic Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.

OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.

EXPOSURE: Respiratory syncytial virus.

MAIN OUTCOMES AND MEASURES: Data were captured on demographics, …

Short-Course Therapy For Urinary Tract Infections In Children: The Scout Randomized Clinical Trial, Theoklis Zaoutis, Nader Shaikh, Brian T Fisher, Susan E Coffin, Sonika Bhatnagar, Kevin J Downes, Jeffrey S Gerber, Timothy R Shope, Judith M Martin, Gysella B Muniz, Michael Green, Jennifer P Nagg, Sage R Myers, Rakesh D Mistry, Shawn O'Connor, Walter Faig, Stephen Black, Elizabeth Rowley, Kellie Liston, Alejandro Hoberman

Faculty, Staff and Student Publications

IMPORTANCE: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI).

OBJECTIVE: To compare the efficacy of standard-course and short-course therapy for children with UTI.

DESIGN, SETTING, PARTICIPANTS: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials.

INTERVENTION: Another …

Variation In Early Anakinra Use And Short-Term Outcomes In Multisystem Inflammatory Syndrome In Children, Joyce C Chang, Cameron C Young, Eyal Muscal, Sara K Sexson Tejtel, Margaret M Newhams, Suden Kucukak, Hillary Crandall, Aline B Maddux, Courtney M Rowan, Natasha B Halasa, Helen A Harvey, Charlotte V Hobbs, Mark W Hall, Michele Kong, Cassyanne L Aguiar, Jennifer E Schuster, Julie C Fitzgerald, Aalok R Singh, Kari Wellnitz, Ryan A Nofziger, Natalie Z Cvijanovich, Elizabeth H Mack, Adam J Schwarz, Sabrina M Heidemann, Jane W Newburger, Laura D Zambrano, Angela P Campbell, Manish M Patel, Adrienne G Randolph, Mary Beth F Son, Overcoming Covid Investigators

Faculty, Staff and Students Publications

OBJECTIVE: Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy.

METHODS: We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days …

Islet: Individual-Specific Reference Panel Recovery Improves Cell-Type-Specific Inference, Hao Feng, Guanqun Meng, Tong Lin, Hemang Parikh, Yue Pan, Ziyi Li, Jeffrey Krischer, Qian Li

Faculty, Staff and Student Publications

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET …

Effectiveness Of Individualized Counseling On The Duration Of Exclusive Breastfeeding: Study Protocol For A Multicenter, Randomized, Parallel, And Open Clinical Trial., Mariana Torreglosa Ruiz, Elisa Da Conceição Rodrigues, Karine Emanuelle Peixoto Oliveira Da Silva, Cynthya Viana De Resende, Michele Curcino Cavalcanti, Luciano Marques Dos Santos, Monika Wernet, Ana Letícia Monteiro Gomes, Marialda Moreira Christoffel, Maria Beatriz Guimarães Raponi, Jéssica Aparecida Da Silva, Jacqueline Faria De Oliveira, Divanice Contim, Ana Linares

Nursing Faculty Publications

BACKGROUND: Despite the benefits of breastfeeding, early weaning is a reality, so less than 50% of children worldwide and in Brazil are on exclusive breastfeeding in the sixth month of life. A strategy to counteract this scenario is breastfeeding counseling. This study aims to verify the effectiveness of individualized counseling by nurses trained in breastfeeding counseling, on the duration of exclusive breastfeeding, compared to standard care.

METHODS: Multicenter, randomized, parallel, and open clinical trial, with primiparous women aged over 18 years, hospitalized in rooming-in wards at participating centers and hemodynamically stable, aware, and oriented, who had a single-fetus pregnancy and …

Pediatric Streptococcal Pharyngitis Testing And Treatment Practices, Amanda Welch

Dissertations

Objective: The purpose of this pilot quality improvement study was to implement SmartPhrases and assess its impact on adherence to the Infectious Disease Society of America (IDSA) guideline for Group A Streptococcus (GAS) pharyngitis testing and treatment in pediatric patients ages 1-16 years old. The aim was to use SmartPhrases to improve adherence with the IDSA guideline by 30% for GAS pharyngitis swabbing and 10% for appropriate antibiotic prescribing in three months.

Methods: A retrospective data analysis approach was used, in reviewing SmartPhrases data from the electronic health records (EHR) in a metropolitan Urgent Care. This data were collected from …

Impact Of Age And School Instruction Mode On Children’S Occupations Early In The Covid-19 Pandemic: A Longitudinal Survey Study, Samuel Nemanich, Gabriel M. Velez, Ann Millard, Anne Pleva

Occupational Therapy Faculty Research and Publications

Importance: The coronavirus disease 2019 (COVID-19) pandemic disrupted participation in routines and daily activities. It is unclear how children reengaged in activities during the pandemic, particularly as a new school year began. Differences in school instruction mode (in person, hybrid, or remote) during the pandemic could further affect activity participation.

Objective: To examine changes in sedentary and nonsedentary activity participation in children and to determine whether school instruction mode was associated with participation.

Setting: Home-based survey of U.S. residents.

Participants: Parents of 208 children (46.2% female) between ages 5 and 18 yr were surveyed at two waves: March through April …

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome, Melissa R Hines, Tristan E Knight, Kevin O Mcnerney, Mark B Leick, Tania Jain, Sairah Ahmed, Matthew J Frigault, Joshua A Hill, Michael D Jain, William T Johnson, Yi Lin, Kris M Mahadeo, Gabriela M Maron, Rebecca A Marsh, Sattva S Neelapu, Sarah Nikiforow, Amanda K Ombrello, Nirav N Shah, Aimee C Talleur, David Turicek, Anant Vatsayan, Sandy W Wong, Marcela V Maus, Krishna V Komanduri, Nancy Berliner, Jan-Inge Henter, Miguel-Angel Perales, Noelle V Frey, David T Teachey, Matthew J Frank, Nirali N Shah

Faculty, Staff and Student Publications

T cell-mediated hyperinflammatory responses, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are now well-established toxicities of chimeric antigen receptor (CAR) T cell therapy. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusion are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal …

Development Of Cancer Surveillance Guidelines In Ataxia Telangiectasia: A Delphi-Based Consensus Survey Of International Experts, Renata Neves, Blanca De Dios Perez, Rafal Panek, Sumit Jagani, Sophie Wilne, Jayesh M Bhatt, Caterina Caputi, Emilia Cirillo, David J Coman, Gregor Dückers, Donald L Gilbert, Mary Kay Koenig, Lobna Mansour, Elizabeth Mcdermott, Micaela Pauni, Claudio Pignata, Susan L Perlman, Oscar Porras, Mariela Betina Porto, Katherine Schon, Pere Soler-Palacin, Sam Nick Russo, Masatoshi Takagi, Marc Tischkowitz, Claire Wainwright, Madhumita Dandapani, Cristine Glazebrook, Mohnish Suri, William P Whitehouse, Robert A Dineen

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T.

DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed …

Barriers To A Successful Healthcare Transition For Individuals With Urea Cycle Disorders, Farah A Ladha, Cynthia Le Mons, William J Craigen, Pilar L Magoulas, Ronit Marom, Andrea M Lewis

Faculty, Staff and Students Publications

The pediatric to adult healthcare transition (HCT) is a process for individuals with chronic health conditions to gradually shift from a pediatric to an adult-oriented care system. Autonomy and self-management skills required for an individual's HCT readiness can be evaluated through the transition readiness assessment questionnaire (TRAQ). Despite general HCT preparation guidelines, little is known about the HCT experience of individuals with a urea cycle disorder (UCD). This is the first study to report the parent or guardian perception of the HCT process in children with a UCD by investigating the stages of transition readiness and transition outcome. We identify …

Realizing The Promise Of Dolutegravir In Effectively Treating Children And Adolescents Living With Hiv In Real-World Settings In 6 Countries In Eastern And Southern Africa, Jason Michael Bacha, Sandile Dlamini, Florence Anabwani, Judith Gwimile, Jacqueline Balungi Kanywa, John Farirai, Menard Bvumbwe, Mabene Tsotako, Teresa Steffy, Diane Nguyen, Jose Euberto Mendez-Reyes, Peter Elyanu, Heather Haq

Faculty, Staff and Students Publications

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs).

METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS).

RESULTS: Among 9419 CALHIV using DTG, …

Pediatric Vitamin D: Pseudo-Hypervitaminosis, Lily Olayinka, Izmarie Poventud-Fuentes, Emily Garnett, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Vitamin D toxicity is rare in pediatric population. Falsely elevated levels of 25-hydroxyvitamin D have been reported as a major challenge with immunoassay methods for quantifying vitamin D metabolites.

CASE PRESENTATION AND METHOD: Here, we present two pediatric cases of falsely elevated 25-hydroxyvitamin D that resulted in unnecessary further testing. We also report significant same-day variation in the measurement of 25-hydroxyvitamin D using the Abbott i2000SR immunoassay. Samples were spun twice and their values were confirmed with the gold standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for confirmation.

CONCLUSION: The addition of a centrifugation step prior to sample testing …

Safety And Efficacy Of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From A Phase 2, Randomized Clinical Trial In Pediatric Participants With Complicated Intra-Abdominal Infection, Carl-Christian A. Jackson, Jason Newland, Nataliia Dementieva, Julia Lonchar, Feng-Hsiu Su, Jennifer A. Huntington, Mekki Bensaci, Myra W. Popejoy, Matthew G. Johnson, Carisa De Anda, Elizabeth G. Rhee, Christopher J. Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole …

Brain Abscess And Stroke In Children And Adults With Hereditary Hemorrhagic Telangiectasia: Analysis Of A Large National Claims Database, Andrew J. White, Itay Marmor, Kate M. Peacock, Katelin B. Nickel, Jessica Zavadil, Margaret A. Olsen

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT.

METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using

RESULTS: …

Divergent Clinical Presentations And Outcomes Among Children And Adolescents With Kaposi Sarcoma In Malawi And Tanzania, Liane R Campbell, Allison Silverstein, Erin Peckham-Gregory, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Jason M Bacha, Carrie L Kovarik, Parth S Mehta, Toni Chanroo, Asulwisye Kapesa, Beatrice Malingoti, Rizine Mzikamanda, Nmazuo W Ozuah, Carl E Allen, Michael E Scheurer, Nader K El-Mallawany

Center for Medical Ethics and Health Policy Staff Publications

Objectives: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach.

Methods: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania.

Results: …

Association Of Area Deprivation Index With Severity Of Covid-19 In Pediatric Patients: A Multisite Study Of Racially And Ethnically Diverse Children, Sebastian Acosta, Srinivasan Suresh, Anna K Ettinger, Fabio Savorgnan, Ananth Annapragada, Nirupama Kannikeswaran, Usha Sethuraman

Faculty, Staff and Students Publications

Area deprivation index (ADI) is associated with the risk of severe COVID-19 in adults. However, this association has not been established in children. Information on ADI, demographics, clinical features, disease severity, and outcomes was analyzed for 3434 children with COVID-19. A multivariate logistic regression revealed that non-Hispanic Asians, extremes of weight, and higher ADI were associated with severe disease.

Biological Rhythms In Covid-19 Vaccine Effectiveness In An Observational Cohort Study Of 1.5 Million Patients, Guy Hazan, Or A. Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey A. Haspel

2020-Current year OA Pubs

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on …

Infection Of Neonatal Mice With The Murine Norovirus Strain Wu23 Is A Robust Model To Study Norovirus Pathogenesis, Amy M Peiper, Emily W Helm, Quyen Nguyen, Matthew Phillips, Caroline G Williams, Dhairya Shah, Sarah Tatum, Neha Iyer, Marco Grodzki, Laura B Eurell, Aqsa Nasir, Megan T Baldridge, Stephanie M Karst

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe, with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. The development of the murine norovirus (MNV) model nearly two decades ago has facilitated progress in understanding host-norovirus interactions and norovirus strain …

Hard To Swallow: A Review Of Interventions To Improve Swallowing Solid Medication, Caryn J Vandenberg, Alyssa Adams, Robyn Bockrath, Sanghee Kim, Giselle Rodriguez, Andrea Fawcett, Ravi Jhaveri

Faculty, Staff and Student Publications

Solid oral medications are preferred over intravenous or liquid formulations; however, difficulty swallowing solid medication remains a common barrier to adherence. Previous reviews have demonstrated limited evidence on interventions to improve solid medication swallowing abilities. PubMed, Medline (OVID), CINAHL, Scopus, and Web of Science databases were searched for interventions to improve the pediatric population's ability to swallow solid medications. We included studies in English published after the latest review, from January 2014 through April 2022, with pediatric patients not having comorbid conditions affecting swallowing ability. The authors independently reviewed each study's sampling strategy, study design, and the strength of outcome …

Extracorporeal Membrane Oxygenation Characteristics And Outcomes In Children And Adolescents With Covid-19 Or Multisystem Inflammatory Syndrome Admitted To Us Icus, Melania M Bembea, Laura L Loftis, Ravi R Thiagarajan, Cameron C Young, Timothy P Mccadden, Margaret M Newhams, Suden Kucukak, Elizabeth H Mack, Julie C Fitzgerald, Courtney M Rowan, Aline B Maddux, Amanda R Kolmar, Katherine Irby, Sabrina Heidemann, Stephanie P Schwartz, Michele Kong, Hillary Crandall, Kevin M Havlin, Aalok R Singh, Jennifer E Schuster, Mark W Hall, Kari A Wellnitz, Mia Maamari, Mary G Gaspers, Ryan A Nofziger, Peter Paul C Lim, Ryan W Carroll, Alvaro Coronado Munoz, Tamara T Bradford, Melissa L Cullimore, Natasha B Halasa, Gwenn E Mclaughlin, Pia S Pannaraj, Natalie Z Cvijanovich, Matt S Zinter, Bria M Coates, Steven M Horwitz, Charlotte V Hobbs, Heda Dapul, Ana Lia Graciano, Andrew D Butler, Manish M Patel, Laura D Zambrano, Angela P Campbell, Adrienne G Randolph

Faculty, Staff and Students Publications

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed.

DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry.

SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021.

PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Monogenic Early-Onset Lymphoproliferation And Autoimmunity: Natural History Of Stat3 Gain-Of-Function Syndrome, Jennifer W Leiding, Tiphanie P Vogel, Valentine G J Santarlas, Rahul Mhaskar, Madison R Smith, Alexandre Carisey, Alexander Vargas-Hernández, Manuel Silva-Carmona, Maximilian Heeg, Anne Rensing-Ehl, Bénédicte Neven, Jérôme Hadjadj, Sophie Hambleton, Timothy Ronan Leahy, Kornvalee Meesilpavikai, Charlotte Cunningham-Rundles, Cullen M Dutmer, Svetlana O Sharapova, Mervi Taskinen, Ignatius Chua, Rosie Hague, Christian Klemann, Larysa Kostyuchenko, Tomohiro Morio, Akaluck Thatayatikom, Ahmet Ozen, Anna Scherbina, Cindy S Bauer, Sarah E Flanagan, Eleonora Gambineri, Lisa Giovannini-Chami, Jennifer Heimall, Kathleen E Sullivan, Eric Allenspach, Neil Romberg, Sean G Deane, Benjamin T Prince, Melissa J Rose, John Bohnsack, Talal Mousallem, Rohith Jesudas, Maria Marluce Dos Santos Vilela, Michael O'Sullivan, Jana Pachlopnik Schmid, Štěpánka Průhová, Adam Klocperk, Matthew Rees, Helen Su, Sami Bahna, Safa Baris, Lisa M Bartnikas, Amy Chang Berger, Tracy A Briggs, Shannon Brothers, Vanessa Bundy, Alice Y Chan, Shanmuganathan Chandrakasan, Mette Christiansen, Theresa Cole, Matthew C Cook, Mukesh M Desai, Ute Fischer, David A Fulcher, Silvanna Gallo, Amelie Gauthier, Andrew R Gennery, José Gonçalo Marques, Frédéric Gottrand, Bodo Grimbacher, Eyal Grunebaum, Emma Haapaniemi, Sari Hämäläinen, Kaarina Heiskanen, Tarja Heiskanen-Kosma, Hal M Hoffman, Luis Ignacio Gonzalez-Granado, Anthony L Guerrerio, Leena Kainulainen, Ashish Kumar, Monica G Lawrence, Carina Levin, Timi Martelius, Olaf Neth, Peter Olbrich, Alejandro Palma, Niraj C Patel, Tamara Pozos, Kahn Preece, Saúl Oswaldo Lugo Reyes, Mark A Russell, Yael Schejter, Christine Seroogy, Jan Sinclair, Effie Skevofilax, Daniel Suan, Daniel Suez, Paul Szabolcs, Helena Velasco, Klaus Warnatz, Kelly Walkovich, Austen Worth, Stat3 Gof Working Group Members, Mikko R J Seppänen, Troy R Torgerson, Georgios Sogkas, Stephan Ehl, Stuart G Tangye, Megan A Cooper, Joshua D Milner, Lisa R Forbes Satter

Faculty, Staff and Students Publications

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity.

OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants.

METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3.

RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median …

In-Hospital Mortality Risk Stratification In Children Aged Under 5 Years With Pneumonia With Or Without Pulse Oximetry: A Secondary Analysis Of The Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Dataset, Shubhada Hooli, Carina King, Eric D Mccollum, Tim Colbourn, Norman Lufesi, Charles Mwansambo, Christopher J Gregory, Somsak Thamthitiwat, Clare Cutland, Shabir Ahmed Madhi, Marta C Nunes, Bradford D Gessner, Tabish Hazir, Joseph L Mathew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Syed Ma Zaman, Raul O Ruvinsky, Marilla Lucero, Cissy B Kartasasmita, Claudia Turner, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Sudha Basnet, Tor A Strand, Mark I Neuman, Luis Martinez Arroyo, Marcela Echavarria, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Angela Gentile, Mandeep Chadha, Siddhivinayak Hirve, Kerry-Ann F O'Grady, Alexey W Clara, Chris A Rees, Harry Campbell, Harish Nair, Jennifer Falconer, Linda J Williams, Margaret Horne, Shamim A Qazi, Yasir Bin Nisar, Pneumonia Research Partnership To Assess Who Recommendations (Prepare) Study Group

Faculty, Staff and Students Publications

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors.

METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors.

RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five …

Incidence Rates Of Medically Attended Covid-19 In Infants Less Than 6 Months Of Age, Isabel Griffin, Stephanie A Irving, Carmen Sofia Arriola, Angela P Campbell, De-Kun Li, Fatimah S Dawood, Caroline Doughty-Skierski, Jeannette R Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Mary Juergens, Venkatesh Kancharla, Allison L Naleway, Gabriella Newes-Adeyi, Erin Nicholson, Roxana Odouli, Lawrence Reichle, Mo Sanyang, Kate Woodworth, Flor M Munoz

Faculty, Staff and Students Publications

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age.

METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test …

The Who Aware (Access, Watch, Reserve) Antibiotic Book And Prevention Of Antimicrobial Resistance, Veronica Zanichelli, Michael Sharland, Bernadette Cappello, Lorenzo Moja, Haileyesus Getahun, Carmem Pessoa-Silva, Hatim Sati, Catharina Van Weezenbeek, Hanan Balkhy, Mariângela Simão, Sumanth Gandra, Benedikt Huttner

2020-Current year OA Pubs

Guidance on the appropriate use of antibiotics for common infections is lacking in many settings. The World Health Organization (WHO) has recently released

Partnering With Patients And Families Living With Chronic Conditions To Coproduce Diagnostic Safety Through Ourdx: A Previsit Online Engagement Tool, Sigall K Bell, Zhiyong J Dong, Catherine M Desroches, Nicholas Hart, Stephen Liu, Brianna Mahon, Long H Ngo, Eric J Thomas, Fabienne Bourgeois

Faculty, Staff and Student Publications

OBJECTIVE: Patients and families are key partners in diagnosis, but methods to routinely engage them in diagnostic safety are lacking. Policy mandating patient access to electronic health information presents new opportunities. We tested a new online tool ("OurDX") that was codesigned with patients and families, to determine the types and frequencies of potential safety issues identified by patients/families with chronic health conditions and whether their contributions were integrated into the visit note.

METHODS: Patients/families at 2 US healthcare sites were invited to contribute, through an online previsit survey: (1) visit priorities, (2) recent medical history/symptoms, and (3) potential diagnostic concerns. …

Risk Factors And Prognostic Significance Of Platelet Count Abnormalities In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Taylor O Kim, Gladstone Airewele, Amanda Grimes, Shaun Bulsara, Erin Peckham, Sebastian R Wanless, Heather Haq, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Michael Scheurer, Jenny Despotovic

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH).

DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014.

METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with …

The Quality And Management Of Penicillin Allergy Labels In Pediatric Primary Care, Margaret G Taylor, Torsten Joerger, Sara Anvari, Yun Li, Jeffrey S Gerber, Debra L Palazzi

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Penicillin allergy labels are the most common drug allergy label. The objective of this study was to describe the quality and management of penicillin allergy labels in the pediatric primary care setting.

METHODS: Retrospective chart review of 500 of 18 015 children with penicillin allergy labels born from January 1, 2010 to June 30, 2020 randomly selected from an outpatient birth cohort from Texas Children's Pediatrics and Children's Hospital of Philadelphia networks. Penicillin allergy risk classification ("not allergy," "low risk," "moderate or high risk," "severe risk," "unable to classify") was determined based on documentation within (1) the …