Medicine and Health Sciences Commons^™

Going Remote: Implementing Digital Research Methods At An Academic Medical Center During Covid-19, Katie E Keenoy, Eric J Lenze, Ginger E Nicol

2020-Current year OA Pubs

COVID-19 has forced medical research institutions to conduct clinical research remotely. Here, we describe how a university's mHealth Research Core helped facilitate the shift to remote research during the COVID-19 pandemic. In 2019 (pre-pandemic), we conducted stakeholder interviews and leadership group sessions to identify, create, and implement resources and core functions to support investigator-initiated mHealth research. Between April 2019 and February 2020, we identified four investigator needs: 1) a

Teaching For Implementation: A Framework For Building Implementation Research And Practice Capacity Within The Translational Science Workforce, Aaron L Leppin, Ana A Baumann, Maria E Fernandez, Brittany N Rudd, Kathleen R Stevens, David O Warner, Bethany M Kwan, Rachel C Shelton

2020-Current year OA Pubs

Implementation science offers a compelling value proposition to translational science. As such, many translational science stakeholders are seeking to recruit, teach, and train an implementation science workforce. The type of workforce that will make implementation happen consists of both implementation researchers and practitioners, yet little guidance exists on how to train such a workforce. We-members of the Advancing Dissemination and Implementation Sciences in CTSAs Working Group-present the Teaching For Implementation Framework to address this gap. We describe the differences between implementation researchers and practitioners and demonstrate what and how to teach them individually and in co-learning opportunities. We briefly comment …

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 …

Temozolomide Chronotherapy In Patients With Glioblastoma: A Retrospective Single-Institute Study, Anna R Damato, Jingqin Luo, Ruth G N Katumba, Grayson R Talcott, Joshua B Rubin, Erik D Herzog, Jian L Campian

2020-Current year OA Pubs

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival.

METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan-Meier method and Cox …

Homotopic Functional Connectivity Disruptions In Glioma Patients Are Associated With Tumor Malignancy And Overall Survival, Andy G S Daniel, Carl D Hacker, John J Lee, Donna Dierker, Joseph B Humphries, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of

METHODS: We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a …

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 …

A Genetic Mouse Model With Postnatal Nf1 And P53 Loss Recapitulates The Histology And Transcriptome Of Human Malignant Peripheral Nerve Sheath Tumor, Akira Inoue, Laura J Janke, Brian L Gudenas, Hongjian Jin, Yiping Fan, Joshua Paré, Michael R Clay, Paul A Northcott, Angela C Hirbe, Xinwei Cao

2020-Current year OA Pubs

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of

METHODS: We combined 2 genetically modified alleles, an

RESULTS: Postnatal

CONCLUSIONS: The NP-Plp model recapitulates human MPNST genetically, histologically, and molecularly.

Inhibition Of Nox1 Mitigates Blood Pressure Increases In Elastin Insufficiency, Angela Troia, Russell H Knutsen, Carmen M Halabi, Daniela Malide, Zu Xi Yu, Amanda Wardlaw-Pickett, Elise K Kronquist, Kit Man Tsang, Attila Kovacs, Robert P Mecham, Beth A Kozel

2020-Current year OA Pubs

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include the

Detection Of Β-Amyloid Positivity In Alzheimer's Disease Neuroimaging Initiative Participants With Demographics, Cognition, Mri And Plasma Biomarkers, Duygu Tosun, James Bollinger, Vitaliy Ovod, Kwasi G Mawuenyega, Randall J Bateman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Perceived Barriers To Assessing Understanding And Appreciation Of Informed Consent In Clinical Trials: A Mixed-Method Study, Erin D Solomon, Jessica Mozersky, Kari Baldwin, Matthew P Wroblewski, Meredith V Parsons, Melody Goodman, James M Dubois

2020-Current year OA Pubs

INTRODUCTION: Participants and research professionals often overestimate how well participants understand and appreciate consent information for clinical trials, and experts often vary in their determinations of participant's capacity to consent to research. Past research has developed and validated instruments designed to assess participant understanding and appreciation, but the frequency with which they are utilized is unknown.

METHODS: We administered a survey to clinical researchers working with older adults or those at risk of cognitive impairment (

RESULTS: We found that using a validated assessment of consent is relatively uncommon, being used by only 44% of researchers who had an opportunity. …

Clinicopathologic Implications Of Complement Genetic Variants In Kidney Transplantation, Zhen Ren, Stephen J Perkins, Latisha Love-Gregory, John P Atkinson, Anuja Java

2020-Current year OA Pubs

Genetic testing has uncovered rare variants in complement proteins associated with thrombotic microangiopathy (TMA) and C3 glomerulopathy (C3G). Approximately 50% are classified as variants of uncertain significance (VUS). Clinical risk assessment of patients carrying a VUS remains challenging primarily due to a lack of functional information, especially in the context of multiple confounding factors in the setting of kidney transplantation. Our objective was to evaluate the clinicopathologic significance of genetic variants in TMA and C3G in a kidney transplant cohort. We used whole exome next-generation sequencing to analyze complement genes in 76 patients, comprising 60 patients with a TMA and …

Unfriendly Fire: How The Tobacco Industry Is Destroying The Future Of Our Children, Andrew Bush, Thomas Ferkol, Et Al.

2020-Current year OA Pubs

Tobacco has long been known to be one of the greatest causes of morbidity and mortality in the adults, but the effects on the foetus and young children, which are lifelong, have been less well appreciated. Developing from this are electronic nicotine delivery systems or vapes, promulgated as being less harmful than tobacco. Nicotine itself is toxic to the foetus, with permanent effects on lung structure and function. Most vapes contain nicotine, but they also contain many other compounds which are inhaled and for which there are no toxicity studies. They also contain known toxic substances, whose use is banned …

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.

Smaller Spared Subcortical Nuclei Are Associated With Worse Post-Stroke Sensorimotor Outcomes In 28 Cohorts Worldwide, Sook-Lei Liew, Catherine E Lang, Anup K Bhattacharya, Et Al.

2020-Current year OA Pubs

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T

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 …

Antibody Profiling Of Patients With Prostate Cancer Reveals Differences In Antibody Signatures Among Disease Stages, Hemanth K Potluri, Tun Lee Ng, Michael A Newton, Jin Zhang, Christopher A Maher, Peter S Nelson, Douglas G Mcneel

2020-Current year OA Pubs

BACKGROUND: Previous studies of prostate cancer autoantibodies have largely focused on diagnostic applications. So far, there have been no reports attempting to more comprehensively profile the landscape of prostate cancer-associated antibodies. Specifically, it is unknown whether the quantity of antibodies or the types of proteins recognized change with disease progression.

METHODS: A peptide microarray spanning the amino acid sequences of the gene products of 1611 prostate cancer-associated genes was synthesized. Serum samples from healthy male volunteers (n=15) and patients with prostate cancer (n=85) were used to probe the array. These samples included patients with various clinical stages of disease: newly …

Spot The Difference: Comparing Results Of Analyses From Real Patient Data And Synthetic Derivatives, Randi E Foraker, Sean C Yu, Aditi Gupta, Andrew P Michelson, Jose A Pineda Soto, Ryan Colvin, Francis Loh, Marin H Kollef, Thomas Maddox, Bradley Evanoff, Hovav Dror, Noa Zamstein, Albert M Lai, Philip R O Payne

2020-Current year OA Pubs

BACKGROUND: Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification.

OBJECTIVES: To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd., Beer Sheva, Israel) for its ability to produce data that can be used for research purposes while obviating privacy and confidentiality concerns.

METHODS: We explored three use cases and tested the robustness of synthetic data by comparing the results of …

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.

Acute Right Ventricular Dysfunction In A Critically Ill Patient With Covid-19, Chakradhar Venkata, Senthil Aruchamy, Jan Kasal

2020-Current year OA Pubs

• Right ventricular dysfunction is common in critically ill patients with COVID-19. • Echocardiography is crucial for diagnosing hemodynamic complications of COVID-19. • Pulmonary embolism and acute cor pulmonale can complicate SARS-CoV-2 infection.