Medicine and Health Sciences Commons^™

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 Randomized, Placebo-Controlled Trial Evaluating Effects Of Lebrikizumab On Airway Eosinophilic Inflammation And Remodelling In Uncontrolled Asthma (Clavier), Cary D Austin, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate-to-severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.

OBJECTIVE: To report safety and efficacy results from enrolled participants with available data from CLAVIER.

METHODS: We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm

RESULTS: There was a baseline …

A Phase 1b Study Of Afm13 In Combination With Pembrolizumab In Patients With Relapsed Or Refractory Hodgkin Lymphoma, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a …

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 …

Periacetabular Osteotomy With Or Without Arthroscopic Management In Patients With Hip Dysplasia: Study Protocol For A Multicenter Randomized Controlled Trial, Geoffrey P Wilkin, Stéphane Poitras, John Clohisy, Etienne Belzile, Ira Zaltz, George Grammatopoulos, Gerd Melkus, Kawan Rakhra, Tim Ramsay, Kednapa Thavorn, Paul E Beaulé

2020-Current year OA Pubs

BACKGROUND: Hip dysplasia is one of the most common causes of hip arthritis. Its incidence is estimated to be between 3.6 and 12.8% (Canadian Institute for Health Information, Hip and knee replacements in Canada, 2017-2018: Canadian joint replacement registry annual report, 2019; Jacobsen and Sonne-Holm, Rheumatology 44:211-8, 2004). The Periacetabular Osteotomy (PAO) has been used successfully for over 30 years (Gosvig et al., J Bone Joint Surg Am 92:1162-9, 2010), but some patients continue to exhibit symptoms post-surgery (Wyles et al., Clin Orthop Relat Res 475:336-50, 2017). A hip arthroscopy, performed using a small camera, allows surgeons to address torn …

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 …

Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is a narrowing of the aorta caused by elastin (ELN) haploinsufficiency. SVAS severity varies among patients with Williams-Beuren syndrome (WBS), a rare disorder that removes one copy of ELN and 25-27 other genes. Twenty percent of children with WBS require one or more invasive and often risky procedures to correct the defect while 30% have no appreciable stenosis, despite sharing the same basic genetic lesion. There is no known medical therapy. Consequently, identifying genes that modify SVAS offers the potential for novel modifier-based therapeutics. To improve statistical power in our rare-disease cohort (N = 104 exomes), …

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

Effects Of Ruxolitinib Cream On Pruritus And Quality Of Life In Atopic Dermatitis: Results From A Phase 2, Randomized, Dose-Ranging, Vehicle- And Active-Controlled Study, Brian S Kim, Kang Sun, Kim Papp, May Venturanza, Adnan Nasir, Michael E. Kuligowski

2020-Current year OA Pubs

BACKGROUND: Atopic dermatitis (AD), a chronic, highly pruritic skin disorder, impairs quality of life (QoL). Janus kinase inhibitors suppress inflammatory and pruritus-associated cytokine signaling in AD.

OBJECTIVE: To report the effects of ruxolitinib (RUX) cream on itch and QoL in AD.

METHODS: A total of 307 adult patients with an Investigator's Global Assessment (score of 2 or 3) and 3% to 20% affected body surface area were randomly assigned for 8 weeks to receive double-blind treatment with RUX (1.5% twice daily, 1.5% once daily, 0.5% once daily, or 0.15% once daily), vehicle twice daily, or triamcinolone cream (0.1% twice daily …

Dupilumab Treatment Results In Early And Sustained Improvements In Itch In Adolescents And Adults With Moderate To Severe Atopic Dermatitis: Analysis Of The Randomized Phase 3 Studies Solo 1 And Solo 2, Ad Adol, And Chronos, Jonathan I. Silverberg, Gil Yosipovitch, Eric L. Simpson, Brian S. Kim, Jashin J. Wu, Laurent Eckert, Isabelle Guillemin, Zhen Chen, Marius Ardeleanu, Ashish Bansal, Mandeep Kaur, Ana B. Rossi, Neil M. H. Graham, Naimish Patel, Abhijit Gadkari

2020-Current year OA Pubs

BACKGROUND: Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD).

OBJECTIVE: To evaluate the timing and effect of dupilumab on itch.

METHODS: Analysis of data from 1505 patients with moderate to severe AD included in 4 randomized controlled studies, treated for up to 52 weeks. Adults received dupilumab 300 mg every 2 weeks or placebo monotherapy (SOLO 1: NCT02277743; SOLO 2: NCT02277769), with concomitant topical corticosteroids (CHRONOS: NCT02260986); adolescents (≥12 to <18 y) were treated with dupilumab monotherapy every 2 weeks (200 mg for baseline weight of <60 kg; 300 mg for baseline weight of ≥60 kg) or placebo (AD ADOL: NCT03054428).

RESULTS: Dupilumab showed significant rapid improvements from baseline in daily Peak Pruritus Numerical Rating Scale scores versus placebo, by day 2 in adults and day 5 in adolescents. …

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 …

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

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 …