Medicine and Health Sciences Commons^™

Electronic Clinical Decision Support For Children With Minor Head Trauma And Intracranial Injuries: A Sociotechnical Analysis, Jacob K Greenberg, Ayodamola Otun, Azzah Nasraddin, Ross C Brownson, Nathan Kuppermann, David D Limbrick, Po-Yin Yen, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Current management of children with minor head trauma (MHT) and intracranial injuries is not evidence-based and may place some children at risk of harm. Evidence-based electronic clinical decision support (CDS) for management of these children may improve patient safety and decrease resource use. To guide these efforts, we evaluated the sociotechnical environment impacting the implementation of electronic CDS, including workflow and communication, institutional culture, and hardware and software infrastructure, among other factors.

METHODS: Between March and May, 2020 semi-structured qualitative focus group interviews were conducted to identify sociotechnical influences on CDS implementation. Physicians from neurosurgery, emergency medicine, critical care, …

Patient-Reported Outcomes From A Randomized, Active-Controlled, Open-Label, Phase 3 Trial Of Burosumab Versus Conventional Therapy In Children With X-Linked Hypophosphatemia, Raja Padidela, Michael P Whyte, Et Al.

2020-Current year OA Pubs

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue …

Real-World Outcomes Of Patients With Locally Advanced Or Metastatic Epithelioid Sarcoma, Mrinal M Gounder, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limited data are available on the real-world effectiveness and safety of systemic therapies for advanced (surgically unresectable and/or metastatic) epithelioid sarcoma (ES).

METHODS: A retrospective medical records review was conducted in patients with advanced ES who were initiating first-line or ≥2 lines of systemic therapy (2000-2017) at 5 US cancer centers. The real-world overall response rate (rwORR), the duration of response (rwDOR), the disease control rate (rwDCR) (defined as stable disease for ≥32 weeks or any duration of response), and progression-free survival (rwPFS) were assessed by radiology reports. Overall survival (OS), rwDOR, and rwPFS were estimated from the time …

Progression Of Pediatric Celiac Disease From Potential Celiac Disease To Celiac Disease: A Retrospective Cohort Study, Shruti Sakhuja, Lori R Holtz

2020-Current year OA Pubs

BACKGROUND: A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease.

METHODS: We performed a retrospective analysis of children (0-18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children's Hospital between 2013 and 2018.

RESULTS: Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6-5) X upper …

Impact Of Spinal Deformity Characteristics On Patient-Reported Outcome Measurement Information System Scores In Patients With Idiopathic Scoliosis Undergoing Posterior Spinal Fusion, Scott J. Luhmann, Mike P. Kelly, Nichelle H. Enata, Kirsten Brouillet, Ernst Etienne, Brian A. Kelly

2020-Current year OA Pubs

INTRODUCTION: The impact of posterior spinal fusion (PSF) on physical function and pain and mental health in pediatric patients as quantified by the Patient-Reported Outcomes Measurement Information System (PROMIS), developed by the National Institute of Health, is largely unknown. The purpose of this study is to report the changes of PROMIS scores for upper extremity (UE), pain interference (PI), mobility (MOB), and peer relationships (PR) after PSF in patients with idiopathic scoliosis (IS), compare postoperative changes in PROMIS PI and Scoliosis Research Society-30 pain scores, and evaluate associations between curve characteristics and PROMIS scores.

METHODS: A retrospective cohort of 122 …

Severity Of Parkinsonism Associated With Environmental Manganese Exposure, Brad A Racette, Gill Nelson, Wendy W Dlamini, Pradeep Prathibha, Jay R Turner, Mwiza Ushe, Harvey Checkoway, Lianne Sheppard, Susan Searles Nielsen

2020-Current year OA Pubs

BACKGROUND: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020.

METHODS: A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an …

Application Of Systems Dynamics And Group Model Building To Identify Barriers And Facilitators To Acute Care Delivery In A Resource Limited Setting, Fiona Muttalib, Ellis Ballard, Josephine Langton, Sara Malone, Yudy Fonseca, Andreas Hansmann, Kenneth Remy, Peter Hovmand, Allan Doctor

2020-Current year OA Pubs

BACKGROUND: Group model building (GMB) is a method to facilitate shared understanding of structures and relationships that determine system behaviors. This project aimed to determine the feasibility of GMB in a resource-limited setting and to use GMB to describe key barriers and facilitators to effective acute care delivery at a tertiary care hospital in Malawi.

METHODS: Over 1 week, trained facilitators led three GMB sessions with two groups of healthcare providers to facilitate shared understanding of structures and relationships that determine system behaviors. One group aimed to identify factors that impact patient flow in the paediatric special care ward. The …

Integrated Proteogenomic Characterization Across Major Histological Types Of Pediatric Brain Cancer, Francesca Petralia, Liang-Bo Wang, Li Ding, Et Al

2020-Current year OA Pubs

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy …

Evaluating The Implementation Of The Switch® School Wellness Intervention And Capacity-Building Process Through Multiple Methods, Gabriella M Mcloughlin, Priscila Candal, Spyridoula Vazou, Joey A Lee, David A Dzewaltowski, Richard R Rosenkranz, Lorraine Lanningham-Foster, Douglas A Gentile, Laura Liechty, Senlin Chen, Gregory J Welk

2020-Current year OA Pubs

BACKGROUND: School wellness programming is important for promoting healthy lifestyles and academic achievement in youth; however, research is needed on methods that can help schools implement and sustain such programs on their own. The purpose of this study was to investigate factors within and outside the school environment that influenced school capacity for implementation and potential sustainability of wellness programming.

METHODS: As part of the School Wellness Integration Targeting Child Health (SWITCH®) intervention, elementary school wellness teams (N = 30) were guided through a capacity-building process focused on promoting the adoption of healthy lifestyle behaviors in students. Data on implementation …

A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh

2020-Current year OA Pubs

BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were …

Factor Structure Of The Opening Minds Stigma Scale For Health Care Providers And Psychometric Properties Of Its Hungarian Version, Dorottya Őri, Sándor Rózsa, Péter Szocsics, Lajos Simon, György Purebl, Zsuzsa Győrffy

2020-Current year OA Pubs

BACKGROUND: The Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a widely used questionnaire to measure the stigmatising attitudes of healthcare providers towards patients with mental health problems. The psychometric properties of the scale; however, have never been investigated in Hungary. We aimed to thoroughly explore the factor structure of the OMS-HC and examine the key psychometric properties of the Hungarian version.

METHODS: The OMS-HC is a self-report questionnaire that measures the overall stigmatising attitude by a total score, and three subscales can be calculated: Attitude, Disclosure and Help-seeking, and Social Distance. Our study population included specialists and …

Inherited Risk For Autism Through Maternal And Paternal Lineage, Dan Bai, Natasha Marrus, Benjamin Hon Kei Yip, Abraham Reichenberg, John N Constantino, Sven Sandin

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is highly familial, with a positively skewed male-to-female ratio that is purported to arise from the so-called female protective effect. A serious implication of a female protective effect is that familial ASD liability would be expected to aggregate asymptomatically in sisters of affected probands, who would incur elevated rates of ASD among their offspring. Currently, there exist no data on second-generation recurrence rates among families affected by ASD.

METHODS: We analyzed data from the Swedish National Patient Register and the Multi-Generation Register for a cohort of children born between 2003 and 2012. ASD was ascertained …

Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al.

2020-Current year OA Pubs

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises …

Safety, Tolerability, And Immunogenicity Of Plasmodium Falciparum Sporozoite Vaccine Administered By Direct Venous Inoculation To Infants And Young Children: Findings From An Age De-Escalation, Dose-Escalation, Double-Blind, Randomized Controlled Study In Western Kenya, Laura C Steinhardt, Ginnie Abarbanell, Et Al.

2020-Current year OA Pubs

BACKGROUND: The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited.

METHODS: We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5-9 years, 13-59 months, and 5-12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 …

Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.

METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition …

Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon.

METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S …

Portable, Field-Based Neuroimaging Using High-Density Diffuse Optical Tomography, Andrew K. Fishell, Ana María Arbeláez, Claudia P. Valdés, Tracy N. Burns-Yocum, Arefeh Sherafati, Edward J. Richter, Margarita Torres, Adam T. Eggebrecht, Christopher D. Smyser, Joseph P. Culver

2020-Current year OA Pubs

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is …

On The Nature Of Monozygotic Twin Concordance And Discordance For Autistic Trait Severity: A Quantitative Analysis, Lauren Castelbaum, Chad M Sylvester, Yi Zhang, Qiongru Yu, John N Constantino

2020-Current year OA Pubs

The characterizing features of autism spectrum disorder (ASD) are continuously distributed in nature; however, prior twin studies have not systematically incorporated this knowledge into estimations of concordance and discordance. We conducted a quantitative analysis of twin-twin similarity for autistic trait severity in three existing data sets involving 366 pairs of uniformly-phenotyped monozygotic (MZ) twins with and without ASD. Probandwise concordance for ASD was 96%; however, MZ trait correlations differed markedly for pairs with ASD trait burden below versus above the threshold for clinical diagnosis, with R

Implications Of New Understandings Of Gliomas In Children And Adults With Nf1: Report Of A Consensus Conference, Roger J Packer, David H Gutmann, Et Al.

2020-Current year OA Pubs

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and …

Three-Dimensional Facial Morphology In Cantú Syndrome, Helen I Roessler, Kathleen Shields, Dorothy K Grange, Nine V A M Knoers, Gijs Van Haaften, Peter Hammond, Mieke M Van Haelst

2020-Current year OA Pubs

Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP-sensitive potassium (K

Late Effects Of Clubfoot Deformity In Adolescent And Young Adult Patients Whose Initial Treatment Was An Extensive Soft-Tissue Release: Topic Review And Clinical Case Series, Jeffrey E Johnson, Thomas A Fortney, Pamela C Luk, Sandra E Klein, Jeremy J Mccormick, Matthew B Dobbs, J Eric Gordon, Perry L Schoenecker

2020-Current year OA Pubs

Children with congenital clubfoot often have residual deformity, pain, and limited function in adolescence and young adulthood. These patients represent a heterogeneous group that often requires an individualized management strategy. This article reviews the available literature on this topic while proposing a descriptive classification system based on a review of patients at our institution who underwent surgery for problems related to previous clubfoot deformity during the period between January 1999 and January 2012. Seventy-two patients (93 feet) underwent surgical treatment for the late effects of clubfoot deformity at an average age of 13 years (range 9 to 19 years). All …

Laser Ablation Of Abnormal Neurological Tissue Using Robotic Neuroblate System (Laantern): Procedural Safety And Hospitalization, Robert C. Rennert, Usman Khan, Jiri Bartek, Stephen B. Tatter, Melvin Field, Brian Toyota, Peter E. Fecci, Kevin Judy, Alireza M. Mohammadi, Patrick Landazuri, Andrew E. Sloan, Albert H. Kim, Eric C. Leuthardt, Clark C. Chen

2020-Current year OA Pubs

BACKGROUND: Stereotactic laser ablation (SLA) has demonstrated potential utility for a spectrum of difficult to treat neurosurgical pathologies in multiple small and/or retrospective single-institutional series. Here, we present the safety profile of SLA of intracranial lesions from the Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN; Monteris Medical) multi-institutional, international prospective observational registry.

OBJECTIVE: To determine the procedural safety of SLA for intracranial lesions.

METHODS: Prospective procedural safety and hospitalization data from the first 100 treated LAANTERN patients was collected and analyzed.

RESULTS: Mean age and baseline Karnofsky Performance Status (KPS) were 51(± 17) yr and 83(± …

Error-Corrected Sequencing Strategies Enable Comprehensive Detection Of Leukemic Mutations Relevant For Diagnosis And Minimal Residual Disease Monitoring, Erin L Crowgey, Nitin Mahajan, Wing Hing Wong, Anilkumar Gopalakrishnapillai, Sonali P Barwe, E Anders Kolb, Todd E Druley

2020-Current year OA Pubs

BACKGROUND: Pediatric leukemias have a diverse genomic landscape associated with complex structural variants, including gene fusions, insertions and deletions, and single nucleotide variants. Routine karyotype and fluorescence in situ hybridization (FISH) techniques lack sensitivity for smaller genomic alternations. Next-generation sequencing (NGS) assays are being increasingly utilized for assessment of these various lesions. However, standard NGS lacks quantitative sensitivity for minimal residual disease (MRD) surveillance due to an inherently high error rate.

METHODS: Primary bone marrow samples from pediatric leukemia (n = 32) and adult leukemia subjects (n = 5), cell line MV4-11, and an umbilical cord sample were utilized for …

Correction Of Respiratory Artifacts In Mri Head Motion Estimates, Damien A. Fair, Abraham Z. Snyder, Andrew N. Van, Jonathan M. Koller, Amy E. Mirro, Jacqueline M Hampton, Babatunde Adeyemo, Timothy O. Laumann, Deanna J. Greene, Deann M. Barch, Steven E. Petersen, Nico U. F. Dosenbach, Et Al.

2020-Current year OA Pubs

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated …