Medicine and Health Sciences Commons^™

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. …

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

Hypoglycaemia Is Reduced With Use Of Inhaled Technosphere ® Insulin Relative To Insulin Aspart In Type 1 Diabetes Mellitus, E R Seaquist, L Blonde, J B Mcgill, S R Heller, D M Kendall, J B Bumpass, F M Pompilio, M L Grant

2020-Current year OA Pubs

AIM: To evaluate the effect of final HbA

METHODS: In the randomized, phase 3, multicentre AFFINITY-1 study, adults (N = 375) who had type 1 diabetes for ≥ 12 months and an HbA

RESULTS: Participants treated with Technosphere Insulin experienced statistically significantly fewer level 1 and 2 hypoglycaemic events and a lower incidence of level 3 hypoglycaemia than participants treated with insulin aspart. The lower rate of hypoglycaemia with Technosphere Insulin was observed across the range of end-of-treatment HbA

CONCLUSIONS: Participants using Technosphere Insulin experienced clinically non-inferior glycaemic control and lower hypoglycaemia rates across a range of HbA

No Difference In Strength And Clinical Outcome Between Early And Late Repair After Achilles Tendon Rupture, Michael R Carmont, Jennifer A Zellers, Annelie Brorsson, Karin Grävare Silbernagel, Jón Karlsson, Katarina Nilsson-Helander

2020-Current year OA Pubs

PURPOSE: This retrospective study aimed to determine the patient-reported and functional outcome of patients with delayed presentation, who had received no treatment until 14 days following injury of Achilles tendon rupture repaired with minimally invasive surgery and were compared with a group of sex- and age-matched patients presenting acutely. Based on the outcomes following delayed presentation reported in the literature, it was hypothesized that outcomes would be inferior for self-reported outcome, tendon elongation, heel-rise performance, ability to return to play, and complication rates than for acutely managed patients.

METHODS: Repair was performed through an incision large enough to permit mobilisation …

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(± …

Associations Between Breast Cancer Subtype And Neighborhood Socioeconomic And Racial Composition Among Black And White Women, Erin Linnenbringer, Arline T Geronimus, Kia L Davis, John Bound, Libby Ellis, Scarlett L Gomez

2020-Current year OA Pubs

PURPOSE: Studies of Black-White differences in breast cancer subtype often emphasize potential ancestry-associated genetic or lifestyle risk factors without fully considering how the social or economic implications of race in the U.S. may influence risk. We assess whether neighborhood racial composition and/or socioeconomic status are associated with odds of triple-negative breast cancer (TNBC) diagnosis relative to the less-aggressive hormone receptor-positive/HER2-negative subtype (HR+ /HER-), and whether the observed relationships vary across women's race and age groups.

METHODS: We use multilevel generalized estimating equation models to evaluate odds of TNBC vs. HR+ /HER2- subtypes in a population-based cohort of 7291 Black and …

Breast Cancer Risk, Worry, And Anxiety: Effect On Patient Perceptions Of False-Positive Screening Results, Janie M. Lee, Kathryn P. Lowry, Jessica E. Cott Chubiz, J. Shannon Swan, Tina Motazedi, Elkan F. Halpern, Anna N. A. Tosteson, G. Scott Gazelle, Karen Donelan

2020-Current year OA Pubs

OBJECTIVE: The impact of mammography screening recall on quality-of-life (QOL) has been studied in women at average risk for breast cancer, but it is unknown whether these effects differ by breast cancer risk level. We used a vignette-based survey to evaluate how women across the spectrum of breast cancer risk perceive the experience of screening recall.

METHODS: Women participating in mammography or breast MRI screening were recruited to complete a vignette-based survey. Using a numerical rating scale (0-100), women rated QOL for hypothetical scenarios of screening recall, both before and after benign results were known. Lifetime breast cancer risk was …

Diroximel Fumarate Demonstrates An Improved Gastrointestinal Tolerability Profile Compared With Dimethyl Fumarate In Patients With Relapsing-Remitting Multiple Sclerosis: Results From The Randomized, Double-Blind, Phase Iii Evolve-Ms-2 Study, Robert T Naismith, Et Al.

2020-Current year OA Pubs

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate approved in the USA for relapsing forms of multiple sclerosis. DRF is converted to monomethyl fumarate, the pharmacologically active metabolite of dimethyl fumarate (DMF). DRF 462 mg and DMF 240 mg produce bioequivalent exposure of monomethyl fumarate and are therefore expected to have similar efficacy/safety profiles; the distinct chemical structure of DRF may contribute to its tolerability profile.

OBJECTIVES: The objective of this study was to compare the gastrointestinal tolerability of DRF and DMF over 5 weeks in patients with relapsing-remitting multiple sclerosis.

METHODS: EVOLVE-MS-2 was a phase III, randomized, double-blind, …

Treatment Of Atopic Dermatitis With Ruxolitinib Cream (Jak1/Jak2 Inhibitor) Or Triamcinolone Cream, Brian S Kim, Michael D Howell, Kang Sun, Kim Papp, Adnan Nasir, Michael E Kuligowski, Incb 18424-206 Study Investigators

2020-Current year OA Pubs

BACKGROUND: Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis.

OBJECTIVE: We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD.

METHODS: In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], …

Negative Pressure Wound Therapy With Instillation: International Consensus Guidelines Update., Paul J Kim, Christopher E Attinger, Thomas Constantine, Brett D Crist, Elizabeth Faust, Christoph R Hirche, Lawrence A Lavery, Valerie J Messina, Norihiko Ohura, Laurie J Punch, Garrett A Wirth, Ibby Younis, Luc Téot

2020-Current year OA Pubs

The use of negative pressure wound therapy with instillation and dwell time (NPWTi-d) has gained wider adoption and interest due in part to the increasing complexity of wounds and patient conditions. Best practices for the use of NPWTi-d have shifted in recent years based on a growing body of evidence and expanded worldwide experience with the technology. To better guide the use of NPWTi-d with all dressing and setting configurations, as well as solutions, there is a need to publish updated international consensus guidelines, which were last produced over 6 years ago. An international, multidisciplinary expert panel of clinicians was …

The Community Structure Of Functional Brain Networks Exhibits Scale-Specific Patterns Of Inter- And Intra-Subject Variability, Richard F Betzel, Maxwell A Bertolero, Evan M Gordon, Caterina Gratton, Nico U F Dosenbach, Danielle S Bassett

2010-2019 OA Pubs

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain's modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time …

Immune Globulin Subcutaneous, Human - Klhw 20% For Primary Humoral Immunodeficiency: An Open-Label, Phase Iii Study, John W Sleasman, William R Lumry, Iftikhar Hussain, H James Wedner, James B Harris, Kecia L Courtney, Elsa Mondou, Jiang Lin, Mark R Stein

2010-2019 OA Pubs

No abstract provided.

Noninvasive Detection Of Graft Injury After Heart Transplant Using Donor-Derived Cell-Free Dna: A Prospective Multicenter Study, Kiran K Khush, Jignesh Patel, Sean Pinney, Andrew Kao, Rami Alharethi, Eugene Depasquale, Gregory Ewald, Peter Berman, Manreet Kanwar, David Hiller, James P Yee, Robert N Woodward, Shelley Hall, Jon Kobashigawa

2020-Current year OA Pubs

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR). Plasma dd-cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd-cfDNA levels were correlated to paired events of biopsy-based diagnosis …

Sexual Violation Of Patients By Physicians: A Mixed-Methods, Exploratory Analysis Of 101 Cases, James M Dubois, Heidi A Walsh, John T Chibnall, Emily E Anderson, Michelle R Eggers, Mobolaji Fowose, Hannah Ziobrowski

2010-2019 OA Pubs

A mixed-method, exploratory design was used to examine 101 cases of sexual violations in medicine. The study involved content analysis of cases to characterize the physicians, patient-victims, the practice setting, kinds of sexual violations, and consequences to the perpetrator. In each case, a criminal law framework was used to examine how motives, means, and opportunity combined to generate sexual misconduct. Finally, cross-case analysis was performed to identify clusters of causal factors that explain specific kinds of sexual misconduct. Most cases involved a combination of five factors: male physicians (100%), older than the age of 39 (92%), who were not board …

White Matter Damage, Neuroinflammation, And Neuronal Integrity In Hand, Aljoharah Alakkas, David B Clifford, Et Al.

2010-2019 OA Pubs

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds …

Developing And Assessing The Feasibility Of A Home-Based Preexposure Prophylaxis Monitoring And Support Program, Aaron J Siegler, Kenneth H Mayer, Albert Y Liu, Rupa R Patel, Lauren M Ahlschlager, Colleen S Kraft, Rossi Fish, Sarah E Wiatrek, Patrick S Sullivan

2010-2019 OA Pubs

We piloted PrEP@Home, a preexposure prophylaxis system of remote laboratory and behavioral monitoring designed to replace routine quarterly follow-up visits with home care to reduce the patient and provider burden. The system was highly acceptable and in-demand for future use, and more than one-third of participants reported greater likelihood of persisting in care if available.

Understanding The Association Between Negative Symptoms And Performance On Effort-Based Decision-Making Tasks: The Importance Of Defeatist Performance Beliefs, L Felice Reddy, William P Horan, Deanna M Barch, Robert W Buchanan, James M Gold, Stephen R Marder, Jonathan K Wynn, Jared Young, Michael F Green

2010-2019 OA Pubs

Effort-based decision-making paradigms are increasingly utilized to gain insight into the nature of motivation deficits. Research has shown associations between effort-based decision making and experiential negative symptoms; however, the associations are not consistent. The current study had two primary goals. First, we aimed to replicate previous findings of a deficit in effort-based decision making among individuals with schizophrenia on a test of cognitive effort. Second, in a large sample combined from the current and a previous study, we sought to examine the association between negative symptoms and effort by including the related construct of defeatist beliefs. The results replicated previous …

White Matter Diffusion Alterations Precede Symptom Onset In Autosomal Dominant Alzheimer's Disease, Miguel Ángel Araque Caballero, Tammie Benzinger, Anne M Fagan, Randall J Bateman, Celeste Karch, John C Morris, Jason Hassenstab, Et Al.

2010-2019 OA Pubs

White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter …

Randomized, Double-Blind, Phase Ii Study Of Temozolomide In Combination With Either Veliparib Or Placebo In Patients With Relapsed-Sensitive Or Refractory Small-Cell Lung Cancer, M Catherine Pietanza, Saiama N Waqar, Et Al

2010-2019 OA Pubs

Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m

Transcription Factor Gata4 Associates With Mesenchymal-Like Gene Expression In Human Hepatoblastoma Cells, Tea Soini, Katja Eloranta, Marjut Pihlajoki, Antti Kyrönlahti, Oyediran Akinrinade, Noora Andersson, Jouko Lohi, Mikko P Pakarinen, David B Wilson, Markku Heikinheimo

2010-2019 OA Pubs

GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor of childhood. However, the molecular and phenotypic consequences of GATA4 expression in hepatoblastoma are not fully understood. We surveyed GATA4 expression in 24 hepatoblastomas using RNA in situ hybridization and immunohistochemistry. RNA interference was used to inhibit GATA4 in human HUH6 hepatoblastoma cells, and changes in cell migration were measured with wound healing and transwell assays. RNA microarray hybridization was performed on control and GATA4 knockdown HUH6 cells, and differentially expressed genes were validated by quantitative polymerase chain reaction or …

Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al.

2010-2019 OA Pubs

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left …

Prevalence, Incidence, And Clearance Of Anal High-Risk Human Papillomavirus Infection Among Hiv-Infected Men In The Sun Study, Pragna Patel, Tim Bush, Erna Milunka Kojic, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, John Hammer, Gerome Escota, Joel M Palefsky, John T Brooks

2010-2019 OA Pubs

BACKGROUND: The natural history of anal human papilloma virus (HPV) infection among human immunodeficiency virus (HIV)-infected men is unknown.

METHODS: Annually, from 2004 to 2012, we examined baseline prevalence, incidence, and clearance of anal HPV infection at 48 months, and associated factors among HIV-infected men.

RESULTS: We examined 403 men who have sex with men (MSM) and 96 men who have sex with women (MSW) (median age 42 years for both, 78% versus 81% prescribed cART, median CD4+ T-lymphocyte cell count 454 versus 379 cells/mm3, and 74% versus 75% had undetectable viral load, respectively). Type 16 prevalence among MSM and …

Insights Into Onchocerca Volvulus Population Biology Through Multilocus Immunophenotyping, Carmelle T Norice-Tra, José Ribeiro, Sasisekhar Bennuru, Michael P Fay, Rahul Tyagi, Makedonka Mitreva, Thomas B Nutman

2010-2019 OA Pubs

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides …

Subcutaneous Peginterferon Β-1a Injection-Site Reaction Experience And Mitigation: Delphi Analysis Of The Allow Study, Barry Hendin, Deren Huang, Sibyl Wray, Robert T Naismith, Sheri Rosenblatt, Javier Zambrano, Brian Werneburg

2010-2019 OA Pubs

AIM: The objective of this Delphi analysis was to obtain consensus on injection-site reaction (ISR) experience and mitigation strategies for patients with relapsing-remitting multiple sclerosis switching from nonpegylated interferons (IFNs) to peginterferon β-1a in the ALLOW Phase IIIb trial using a three-step approach.

METHODS: Study investigators and coordinators from investigative sites enrolling four or more patients in ALLOW participated in three rounds of questionnaires and interviews.

RESULTS: Respondents (n = 37) agreed that the most common ISR, erythema, was not disruptive to daily activities. Patient education, as a conversation with a clinician about ISR potential, was recommended.

CONCLUSION: The consensus …