Digital Commons Network^™

Improved Gastrointestinal Profile With Diroximel Fumarate Is Associated With A Positive Impact On Quality Of Life Compared With Dimethyl Fumarate: Results From The Randomized, Double-Blind, Phase Iii Evolve-Ms-2 Study, Annette Wundes, Sibyl Wray, Ralf Gold, Barry A Singer, Elzbieta Jasinska, Tjalf Ziemssen, Jerome De Seze, Pavle Repovic, Hailu Chen, Jerome Hanna, Jordan Messer, Catherine Miller, Robert T Naismith

2020-Current year OA Pubs

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate approved for relapsing forms of multiple sclerosis (MS). DRF demonstrated significantly improved gastrointestinal (GI) tolerability

METHODS: A

RESULTS: In total, 504 patients (DRF,

CONCLUSIONS: The improved GI tolerability with DRF translated into clinically meaningful benefits to QoL, as patients experienced less impact on daily life and work and required less concomitant symptomatic medication use.

TRIAL REGISTRATION: [ClinicalTrials.gov identifier: NCT03093324].

Veterans Health Administration's Whole Health System Of Care: Supporting The Health, Well-Being, And Resiliency Of Employees, Kavitha P Reddy, Tamara M Schult, Alison M Whitehead, Barbara G Bokhour

2020-Current year OA Pubs

The Veterans Health Administration (VHA) is implementing a Whole Health System (WHS) of care that empowers and equips Veterans to take charge of their health and well-being and live their lives to the fullest, and increasingly leaders recognize the need and value in implementing a similar approach to support the health and well-being of employees. The purpose of this paper is to do the following: 1) provide an overview of the WHS of care in VHA and applicability in addressing employee resiliency; 2) provide a brief history of employee well-being efforts in VHA to date; 3) share new priorities from …

Climate Change And Antibiotic Resistance: A Deadly Combination, Jason P Burnham

2020-Current year OA Pubs

Climate change is driven primarily by humanity's use of fossil fuels and the resultant greenhouse gases from their combustion. The effects of climate change on human health are myriad and becomingly increasingly severe as the pace of climate change accelerates. One relatively underreported intersection between health and climate change is that of infections, particularly antibiotic-resistant infections. In this perspective review, the aspects of climate change that have already, will, and could possibly impact the proliferation and dissemination of antibiotic resistance are discussed.

Immunotherapy As A Treatment Strategy In Advanced Stage And Recurrent Endometrial Cancer: Review Of Current Phase Iii Immunotherapy Clinical Trials, Ramez N Eskander, Matthew A Powell

2020-Current year OA Pubs

The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer.

Anabolic Resistance Of Muscle Protein Turnover Comes In Various Shapes And Sizes, Kevin J M Paulussen, Colleen F Mckenna, Joseph W Beals, Kenneth R Wilund, Amadeo F Salvador, Nicholas A Burd

2020-Current year OA Pubs

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and …

Convalescent Plasma Therapy For Covid-19: A Graphical Mosaic Of The Worldwide Evidence, Stephen A Klassen, Brenda J Grossman, Jeffrey P Henderson, Et Al.

2020-Current year OA Pubs

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but …

Immune Cell Analysis Of Pilocytic Astrocytomas Reveals Sexually Dimorphic Brain Region-Specific Differences In T-Cell Content, Jie Chen, Namita Sinha, Olivia Cobb, Collin Liu, Ayca Ersen, Joanna J Phillips, Tarik Tihan, David H Gutmann, Sonika Dahiya

2020-Current year OA Pubs

No abstract provided.

Profiles Of Hiv Care Disruptions Among Adult Patients Lost To Follow-Up In Zambia: A Latent Class Analysis, Aaloke Mody, Kombatende Sikombe, Laura K. Beres, Sandra Simbeza, Njekwa Mukamba, Ingrid Eshun-Wilson, Sheree Schwartz, Jake Pry, Nancy Padian, Charles B. Holmes, Carolyn Bolton-Moore, Izukanji Sikazwe, Elvin H. Geng

2020-Current year OA Pubs

BACKGROUND: Patients report varied barriers to HIV care across multiple domains, but specific barrier patterns may be driven by underlying, but unobserved, behavioral profiles.

METHODS: We traced a probability sample of patients lost to follow-up (>90 days late) as of July 31, 2015 from 64 clinics in Zambia. Among those found alive, we ascertained patient-reported reasons for care disruptions. We performed latent class analysis to identify patient subgroups with similar patterns of reasons reported and assessed the association between class membership and care status (ie, disengaged versus silently transferred to a new site).

RESULTS: Among 547 patients, we identified …

Exploring Intentional Medication Non-Adherence In Patients With Systemic Lupus Erythematosus: The Role Of Physician-Patient Interactions, Jerik Leung, Elizabeth A Baker, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: Medication non-adherence contributes to worse health outcomes among SLE patients. The underlying mechanisms that drive medication non-adherence are poorly understood. The purpose of this study was to explore possible mechanisms of medication non-adherence by eliciting patient experiences.

METHODS: Consented adult patients with ACR- or SLICC-classified SLE were recruited. Ten semi-structured interviews were conducted across six participants. Interviews were audio recorded, transcribed, and analysed using an iterative process. The findings were presented to an interactive public forum with SLE patients, family members and friends of patients, and health-care professionals to assess validity and for elaboration of the concepts developed.

RESULTS: …

Nonliteral Language Processing Across The Lifespan, Kathrin Rothermich, Cristal Giorio, Sharon Falkins, Lindsay Leonard, Angela Roberts

2020-Current year OA Pubs

Studies investigating the effects of aging on nonliteral language processing have mainly focused on one sensory modality, for example written vignettes. In the current study, we used a video-based task to examine the effect of healthy aging on social communication perception using a novel database called RISC (Relation Inference in Social Communication). By means of an online recruitment platform, we asked young, middle-aged, and older adults between the ages of 18 and 76 (N = 100) to evaluate videos of actors using different forms of literal and nonliteral language, such as sarcasm or teasing. The participants' task was to infer …

Context-Responsive Anticoagulation Reduces Complications In Pediatric Extracorporeal Membrane Oxygenation, John C Lin, Lauren M Barron, Adam M Vogel, Ryan M Colvin, Sirine A Baltagi, Allan Doctor, Avihu Z Gazit, Mary Mehegan, Nicole O'Connor, Ahmed S Said, Mark Shepard, Michael Wallendorf, Philip C Spinella

2020-Current year OA Pubs

No abstract provided.

The Genomics Of Heart Failure: Design And Rationale Of The Hermes Consortium, R. Thomas Lumbers, Douglas Mann, Et Al.

2020-Current year OA Pubs

No abstract provided.

Human Cortical Serotonin 2a Receptor Occupancy By Psilocybin Measured Using [11c]Mdl 100,907 Dynamic Pet And A Resting-State Fmri-Based Brain Parcellation, Frederick S Barrett, Yun Zhou, Theresa M Carbonaro, Joshua M Roberts, Gwenn S Smith, Roland R Griffiths, Dean F Wong

2020-Current year OA Pubs

Psilocybin (a serotonin 2A, or 5-HT

Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence And Α-Diversity But Decreases Β-Diversity In The Gut Microbiome Of Human Immunodeficiency Virus-Exposed, Uninfected Infants, Alaric W D'Souza, Eshia Moodley-Govender, Bertram Berla, Tejas Kelkar, Bin Wang, Xiaoqing Sun, Brodie Daniels, Anna Coutsoudis, Indi Trehan, Gautam Dantas

2020-Current year OA Pubs

BACKGROUND: Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined.

METHODS: We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants.

RESULTS: Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway …

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 …

A Triple-Drug Treatment Regimen To Accelerate Elimination Of Lymphatic Filariasis: From Conception To Delivery, Gary J Weil, Julie A Jacobson, Jonathan D King

2020-Current year OA Pubs

The Global Programme to Eliminate Lymphatic Filariasis (LF) is using mass drug administration (MDA) of antifilarial medications to treat filarial infections, prevent disease and interrupt transmission. Almost 500 million people receive these medications each year. Clinical trials have recently shown that a single dose of a triple-drug combination comprised of ivermectin, diethylcarbamazine and albendazole (IDA) is dramatically superior to widely used two-drug combinations for clearing larval filarial parasites from the blood of infected persons. A large multicenter community study showed that IDA was well-tolerated when it was provided as MDA. IDA was rapidly advanced from clinical trial to policy and …

Longitudinal Care Cascade Outcomes Among People Eligible For Antiretroviral Therapy Who Are Newly Linking To Care In Zambia: A Multistate Analysis, Aaloke Mody, David V Glidden, Ingrid Eshun-Wilson, Kombatende Sikombe, Sandra Simbeza, Njekwa Mukamba, Paul Somwe, Laura K Beres, Jake Pry, Carolyn Bolton-Moore, Nancy Padian, Charles B Holmes, Izukanji Sikazwe, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Retention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time.

METHODS: We analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last …

Conversational Ontology Operator: Patient-Centric Vaccine Dialogue Management Engine For Spoken Conversational Agents, Muhammad Amith, Rebecca Z Lin, Licong Cui, Dennis Wang, Anna Zhu, Grace Xiong, Hua Xu, Kirk Roberts, Cui Tao

2020-Current year OA Pubs

BACKGROUND: Previously, we introduced our Patient Health Information Dialogue Ontology (PHIDO) that manages the dialogue and contextual information of the session between an agent and a health consumer. In this study, we take the next step and introduce the Conversational Ontology Operator (COO), the software engine harnessing PHIDO. We also developed a question-answering subsystem called Frankenstein Ontology Question-Answering for User-centric Systems (FOQUS) to support the dialogue interaction.

METHODS: We tested both the dialogue engine and the question-answering system using application-based competency questions and questions furnished from our previous Wizard of OZ simulation trials.

RESULTS: Our results revealed that the dialogue …

Whole Health Options And Pain Education (Whope): A Pragmatic Trial Comparing Whole Health Team Vs Primary Care Group Education To Promote Nonpharmacological Strategies To Improve Pain, Functioning, And Quality Of Life In Veterans-Rationale, Methods, And Implementation, Karen H Seal, Kavitha Reddy, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care.

DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, …

Global Hypermethylation Of Intestinal Epithelial Cells Is A Hallmark Feature Of Neonatal Surgical Necrotizing Enterocolitis, Misty Good, Tianjiao Chu, Patricia Shaw, Lora Mcclain, Austin Chamberlain, Carlos Castro, Jamie M Rimer, Belgacem Mihi, Qingqing Gong, Lila S Nolan, Krista Cooksey, Laura Linneman, Pranjal Agrawal, David N Finegold, David Peters

2020-Current year OA Pubs

BACKGROUND: Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.

METHODS: Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of …

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 …

Perspectives Of Scientists On Disseminating Research Findings To Non-Research Audiences, Demetria M Mcneal, Russell E Glasgow, Ross C Brownson, Daniel D Matlock, Pamela N Peterson, Stacie L Daugherty, Christopher E Knoepke

2020-Current year OA Pubs

BACKGROUND: Little is known about practices used to disseminate findings to non-research, practitioner audiences. This study describes the perspectives, experience and activities of dissemination & implementation (D&I) scientists around disseminating their research findings.

METHODS: The study explored D&I scientists' experiences and recommendations for assessment of dissemination activities to non-research audiences. Existing list serves were used to recruit scientists. Respondents were asked three open-ended questions on an Internet survey about dissemination activities, recommendations for changing evaluation systems and suggestions to improve their own dissemination of their work.

RESULTS: Surveys were completed by 159 scientists reporting some training, funding and/or publication history …

Roxadustat For Ckd-Related Anemia In Non-Dialysis Patients, Daniel W Coyne, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis.

METHODS: ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo. Patients were initially dosed thrice weekly; dose was titrated to achieve a hemoglobin level ≥11.0 g/dl, followed by titration for maintenance. The primary endpoints were change in hemoglobin (weeks 28-52) and proportion of patients achieving a hemoglobin response (hemoglobin ≥11.0 g/dl …

Approaches To Aggressive B-Cell Lymphomas In Less Fit Patients, Nancy L Bartlett

2020-Current year OA Pubs

Treating unfit patients with aggressive B-cell lymphoma poses the dilemma of balancing potential cure while minimizing toxicity because of frailty and comorbidities. Age greater than 80 years and common comorbidities such as cardiovascular disease and poorly controlled diabetes mellitus often preclude the use of full-dose anthracyclines and steroids, the backbones of standard regimens for aggressive B-cell lymphomas. Assessing patient fitness remains subjective, with no consensus on best practice or how to integrate assessment tools into decision making. Incorporation of prephase steroids for all unfit patients may markedly improve performance status with consideration of standard dose therapy, especially in patients less …

Comparing The Effects Of Hiv Self-Testing To Standard Hiv Testing For Key Populations: A Systematic Review And Meta-Analysis, T Charles Witzel, Ingrid Eshun-Wilson, Muhammad S Jamil, Nerissa Tilouche, Carmen Figueroa, Cheryl C Johnson, David Reid, Rachel Baggaley, Nandi Siegfried, Fiona M Burns, Alison J Rodger, Peter Weatherburn

2020-Current year OA Pubs

BACKGROUND: We update a previous systematic review to inform new World Health Organization HIV self-testing (HIVST) recommendations. We compared the effects of HIVST to standard HIV testing services to understand which service delivery models are effective for key populations.

METHODS: We did a systematic review of randomised controlled trials (RCTs) which compared HIVST to standard HIV testing in key populations, published from 1 January 2006 to 4 June 2019 in PubMed, Embase, Global Index Medicus, Social Policy and Practice, PsycINFO, Health Management Information Consortium, EBSCO CINAHL Plus, Cochrane Library and Web of Science. We extracted study characteristic and outcome data …

Lower Survival After Coronary Artery Bypass In Patients Who Had Atrial Fibrillation Missed By Widely Used Definitions, Giovanni Filardo, Benjamin D Pollock, Briget Da Graca, Danielle M Sass, Teresa K Phan, Debbie E Montenegro, Gorav Ailawadi, Vinod H Thourani, Ralph J Damiano Jr

2020-Current year OA Pubs

OBJECTIVE: To investigate the impact of limiting the definition of post-coronary artery bypass graft (CABG) atrial fibrillation (AF) to AF/flutter requiring treatment-as in the Society of Thoracic Surgeons' (STS) database- on the association with survival.

PATIENTS AND METHODS: We assessed in-hospital incidence of post-CABG AF in 7110 consecutive isolated patients with CABG without preoperative AF at 4 hospitals (January 1, 2004 to December 31, 2010). Patients with ≥1 episode of post-CABG AF detected via continuous in-hospital electrocardiogram (ECG)/telemetry monitoring documented by physicians were assigned to the following: Group 1, identified as having post-CABG AF in STS data and Group 2, …

International Council For Standardization In Haematology (Icsh) Recommendations For Laboratory Measurement Of Adamts13, Ian Mackie, Ilaria Mancini, Joshua Muia, Johanna Kremer Hovinga, Sukesh Nair, Sam Machin, Ross Baker

2020-Current year OA Pubs

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), by the ADAMTS13 Assay Working Group, which comprises an international group of both clinical and laboratory experts. The document provides recommendations on best practice for the performance of ADAMTS13 assays in clinical laboratories. ADAMTS13 assays support the differential diagnosis of thrombotic microangiopathies and have utility in the management of thrombotic thrombocytopenic purpura (TTP). There are three types of assay: activity, antigen and autoantibody/inhibitor assays. Methods for activity assays differ in terms of sensitivity, specificity, precision and turnaround time. The most widely used assays involve …

Cardiac Biomarkers During Cancer Therapy: Practical Applications For Cardio-Oncology, Jose A Alvarez-Cardona, Kathleen W Zhang, Joshua D Mitchell, Vlad G Zaha, Michael J Fisch, Daniel J Lenihan

2020-Current year OA Pubs

No abstract provided.

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 …

Sequence Analysis In Bos Taurus Reveals Pervasiveness Of X-Y Arms Races In Mammalian Lineages, Jennifer F Hughes, Colin Kremitzki, Catrina Fronick, Tina A Graves-Lindsay, Lucinda Fulton, Wesley C Warren, Richard K Wilson, Et Al.

2020-Current year OA Pubs

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of