Medicine and Health Sciences Commons^™

Evaluating The Implementation Of A Multi-Level Mhealth Study To Improve Hydroxyurea Utilization In Sickle Cell Disease, J S Hankins, A A King, A A Baumann, L M. Klesges, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the …

It Is Time To Define An Organizational Model For The Prevention And Management Of Infections Along The Surgical Pathway: A Worldwide Cross-Sectional Survey, Massimo Sartellli, John E. Mazuski, Et Al.

2020-Current year OA Pubs

No abstract provided.

Mega-Analysis Methods In Enigma: The Experience Of The Generalized Anxiety Disorder Working Group, André Zugman, Jennifer Harper, Michael Myers, Michael T Perino, Qiongru Yu, Chad M Sylvester, Et Al.

2020-Current year OA Pubs

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as …

Evaluation Of The Khorana Score For Prediction Of Venous Thromboembolism In Patients With Multiple Myeloma, Kristen M Sanfilippo, Kenneth R Carson, Tzu-Fei Wang, Suhong Luo, Natasha Edwin, Nicole Kuderer, Jesse M Keller, Brian F Gage

2020-Current year OA Pubs

BACKGROUND: Guidelines recommend thromboprophylaxis for patients with multiple myeloma (MM) at high risk for venous thromboembolism (VTE). However, the optimal risk prediction model for VTE in MM remains unclear. Khorana et al developed a VTE risk score (Khorana score) in ambulatory cancer patients receiving chemotherapy. We aimed to evaluate the predictive ability of the Khorana score in patients with MM.

METHODS: We identified patients with MM within the Veterans Affairs health care system between 2006 and 2013. The Khorana score was calculated before treatment initiation. Using logistic regression, the relationship between risk group and VTE was assessed at 3 and …

Animal Source Foods, Rich In Essential Amino Acids, Are Important For Linear Growth And Development Of Young Children In Low- And Middle-Income Countries, Panam Parikh, Richard Semba, Mark Manary, Sumathi Swaminathan, Emorn Udomkesmalee, Rolf Bos, Bee Koon Poh, Nipa Rojroongwasinkul, Jan Geurts, Rini Sekartini, Tran Thuy Nga

2020-Current year OA Pubs

Growth faltering under 5 years of age is unacceptably high worldwide, and even more children, while not stunted, fail to reach their growth potential. The time between conception and 2 years of age is critical for development. The period from 6 to 23 months, when complementary foods are introduced, coincides with a time when growth faltering and delayed neurocognitive developments are most common. Fortunately, this is also the period when diet exercises its greatest influence. Growing up in an adverse environment, with a deficient diet, as typically seen in low- and middle-income countries (LMICs), hampers growth and development of children …

Developing Real-World Evidence From Real-World Data: Transforming Raw Data Into Analytical Datasets, Lisa Bastarache, Jeffrey S Brown, James J Cimino, David A Dorr, Peter J Embi, Philip R O Payne, Adam B Wilcox, Mark G Weiner

2020-Current year OA Pubs

Development of evidence-based practice requires practice-based evidence, which can be acquired through analysis of real-world data from electronic health records (EHRs). The EHR contains volumes of information about patients-physical measurements, diagnoses, exposures, and markers of health behavior-that can be used to create algorithms for risk stratification or to gain insight into associations between exposures, interventions, and outcomes. But to transform real-world data into reliable real-world evidence, one must not only choose the correct analytical methods but also have an understanding of the quality, detail, provenance, and organization of the underlying source data and address the differences in these characteristics across …

Higher Amyloid Is Associated With Greater Loneliness Among Cognitively Normal Older Adults During The Covid-19 Pandemic [Version 2; Peer Review: 2 Approved], Abigail Kehrer-Dunlap, Rebecca Bollinger, Szu-Wei Chen, Audrey Keleman, Regina Thompson, Anne Fagan, Beau Ances, Susan Stark

2020-Current year OA Pubs

BACKGROUND: Loneliness has been associated with several consequences, including increased risk of developing Alzheimer disease (AD). Loneliness may arise during the preclinical phase of AD, but little is known about the relationship between loneliness and amyloid accumulation consistent with preclinical AD. Therefore, the purpose of this study was to examine the relationship between amyloid accumulation and subjective experiences of loneliness among cognitively normal older adults during the COVID-19 pandemic.

METHODS: A global Clinical Dementia Rating

RESULTS: The 108 participants had a mean age of 75.0 and an average amyloid accumulation of 22.2 ± 31.9. Mean UCLA Loneliness Scale scores were …

A Promising Genetic Target For A Deadly Disease: Single Immunoglobulin Interleukin 1 (Sigirr) Mutations In Necrotizing Enterocolitis, Misty Good, Camilia R Martin

2020-Current year OA Pubs

No abstract provided.

Automatic Wide Complex Tachycardia Differentiation Using Mathematically Synthesized Vectorcardiogram Signals, Anthony H Kashou, Sarah Lococo, Trevon D Mcgill, Christopher M Evenson, Abhishek J Deshmukh, David O Hodge, Daniel H Cooper, Sandeep S Sodhi, Phillip S Cuculich, Samuel J Asirvatham, Peter A Noseworthy, Christopher V Desimone, Adam M May

2020-Current year OA Pubs

BACKGROUND: Automated wide complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) may be accomplished using novel calculations that quantify the extent of mean electrical vector changes between the WCT and baseline electrocardiogram (ECG). At present, it is unknown whether quantifying mean electrical vector changes within three orthogonal vectorcardiogram (VCG) leads (X, Y, and Z leads) can improve automated VT and SWCT classification.

METHODS: A derivation cohort of paired WCT and baseline ECGs was used to derive five logistic regression models: (i) one novel WCT differentiation model (i.e., VCG Model), (ii) three previously developed WCT …

Co-Clinical Fdg-Pet Radiomic Signature In Predicting Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Sudipta Roy, Timothy D Whitehead, Shunqiang Li, Foluso O Ademuyiwa, Richard L Wahl, Farrokh Dehdashti, Kooresh I Shoghi

2020-Current year OA Pubs

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A …

Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al.

2020-Current year OA Pubs

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen …

Semaphorin-Plexin Signaling: From Axonal Guidance To A New X-Linked Intellectual Disability Syndrome, Jacqueline L Steele, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. The clinical manifestations of semaphorin/plexin neurodevelopmental disorders have been less widely explored. This study describes the neurological and neurodevelopmental phenotypes of boys with maternally inherited hemizygous PLXNA3 variants.

METHODS: Data-sharing through GeneDx and GeneMatcher allowed identification of individuals with autism or intellectual disabilities (autism/ID) and hemizygous …

Automated Detection Of Vaping-Related Tweets On Twitter During The 2019 Evali Outbreak Using Machine Learning Classification, Yang Ren, Dezhi Wu, Avineet Singh, Erin Kasson, Ming Huang, Patricia Cavazos-Rehg

2020-Current year OA Pubs

There are increasingly strict regulations surrounding the purchase and use of combustible tobacco products (i.e., cigarettes); simultaneously, the use of other tobacco products, including e-cigarettes (i.e., vaping products), has dramatically increased. However, public attitudes toward vaping vary widely, and the health effects of vaping are still largely unknown. As a popular social media, Twitter contains rich information shared by users about their behaviors and experiences, including opinions on vaping. It is very challenging to identify vaping-related tweets to source useful information manually. In the current study, we proposed to develop a detection model to accurately identify vaping-related tweets using machine …

Modulation Of Mirisc-Mediated Gene Silencing In Eukaryotes, Courtney F Jungers, Sergej Djuranovic

2020-Current year OA Pubs

Gene expression is regulated at multiple levels in eukaryotic cells. Regulation at the post-transcriptional level is modulated by various

Isotopically Nonstationary 13c Metabolic Flux Analysis In Resting And Activated Human Platelets, Cara L Sake, Alexander J Metcalf, Michelle Meagher, Jorge Di Paola, Keith B Neeves, Nanette R Boyle

2020-Current year OA Pubs

Platelet metabolism is linked to platelet hyper- and hypoactivity in numerous human diseases. Developing a detailed understanding of the link between metabolic shifts and platelet activation state is integral to improving human health. Here, we show the first application of isotopically nonstationary

Outcomes Following In-Hospital Cardiopulmonary Resuscitation In People Receiving Maintenance Dialysis, Fahad Saeed, Haris F Murad, Richard E Wing, Jianbo Li, Jesse D Schold, Kevin A Fiscella

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Previous studies showing poor cardiopulmonary resuscitation (CPR) outcomes in the dialysis population have largely been derived from claims data and are somewhat limited by a lack of detailed characterization of CPR events. We aimed to analyze CPR-related outcomes in individuals receiving maintenance dialysis.

STUDY DESIGN: Retrospective chart review.

SETTING & PARTICIPANTS: Using electronic medical records from a single academic health care system, we identified all hospitalized adult patients receiving maintenance dialysis who had undergone in-hospital CPR between 2006 and 2014.

EXPOSURE: Initial in-hospital CPR.

OUTCOMES: Overall survival, predictors of unsuccessful CPR, predictors of death during the same …

Calorie Restriction Improves Lipid-Related Emerging Cardiometabolic Risk Factors In Healthy Adults Without Obesity: Distinct Influences Of Bmi And Sex From Calerie™ A Multicentre, Phase 2, Randomised Controlled Trial, Kim M Huffman, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21-50 years), normal weight healthy population undergoing …

Psychiatric Diagnoses And Medications In Wolfram Syndrome, Angela M Reiersen, Jacob S Noel, Tasha Doty, Richa A Sinkre, Anagha Narayanan, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the

OBJECTIVE: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome.

METHOD: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups.

RESULTS: Study participants with Wolfram …

Job-Exposure Matrix: A Useful Tool For Incorporating Workplace Exposure Data Into Population Health Research And Practice, Alexis Descatha, Marc Fadel, Grace Sembajwe, Susan Peters, Bradley A Evanoff

2020-Current year OA Pubs

Workplace exposures to physical, chemical, and psychosocial factors account for a large burden of chronic diseases. Obtaining useful estimates of current and past workplace exposures is challenging, particularly in large general population studies. Job-exposure matrices (JEMs) are a useful tool for exposure assessment, particularly when no individual level exposure data are available. A JEM provides a cross-tabulation of job titles (sometimes combined with industry) and estimated exposures to workers carrying out these jobs during different time periods. The major limitation of JEMs is that they do not account for individual variation in exposures within the same job. This limitation is …

Preclinical Antibody-Pet Imaging Of Pd-L1, Emma L Brown, Rachel A Deweerd, Abbey Zidel, Patricia M R Pereira

2020-Current year OA Pubs

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission …

Sustainability Of Breastfeeding Interventions To Reduce Child Mortality Rates In Low, Middle-Income Countries: A Systematic Review Of Randomized Controlled Trials, Alexis Engelhart, Stacey Mason, Ucheoma Nwaozuru, Chisom Obiezu-Umeh, Victoria Carter, Thembekile Shato, Titilola Gbaja-Biamila, David Oladele, Juliet Iwelunmor

2020-Current year OA Pubs

Child mortality is the lowest it has ever been, but the burden of death in low- and middle-income countries (LMICs) is still prevalent, and the numbers average above the global mean. Breastfeeding contributes to the reduction of child mortality by improving chance of survival beyond childhood. Therefore, it is essential to examine how evidence-based breastfeeding interventions are being maintained in resource-constrained settings. Guided by Scheirer and Dearing's sustainability framework, the aim of this systematic review was to explore how evidence-based breastfeeding interventions implemented to address child mortality in LMICs are sustained. The literature search included randomized controlled trials (RCTs) of …

Sustainability In Pediatric Hospitals: An Exploration At The Intersection Of Quality Improvement And Implementation Science, Sara Malone, Jason Newland, Sapna R Kudchadkar, Kim Prewitt, Virginia Mckay, Beth Prusaczyk, Enola Proctor, Ross C Brownson, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Although new evidence-based practices are frequently implemented in clinical settings, many are not sustained, limiting the intended impact. Within implementation science, there is a gap in understanding sustainability. Pediatric healthcare settings have a robust history of quality improvement (QI), which includes a focus on continuation of change efforts. QI capability and sustainability capacity, therefore, serve as a useful concept for connecting the broader fields of QI and implementation science to provide insights on improving care. This study addresses these gaps in understanding of sustainability in pediatric settings and its relationship to QI.

METHODS: This is a cross-sectional observational study …

Il-1 Reprogramming Of Adult Neural Stem Cells Limits Neurocognitive Recovery After Viral Encephalitis By Maintaining A Proinflammatory State, Allison L Soung, Veronica A Davé, Charise Garber, Eric D Tycksen, Lauren L Vollmer, Robyn S Klein

2020-Current year OA Pubs

Innate immune responses to emerging RNA viruses are increasingly recognized as having significant contributions to neurologic sequelae, especially memory disorders. Using a recovery model of West Nile virus (WNV) encephalitis, we show that, while macrophages deliver the antiviral and anti-neurogenic cytokine IL-1β during acute infection; viral recovery is associated with continued astrocyte inflammasome-mediated production of inflammatory levels of IL-1β, which is maintained by hippocampal astrogenesis via IL-1R1 signaling in neural stem cells (NSC). Accordingly, aberrant astrogenesis is prevented in the absence of IL-1 signaling in NSC, indicating that only newly generated astrocytes exert neurotoxic effects, preventing synapse repair and promoting …

Genome-Wide Analysis Of Mitochondrial Dna Copy Number Reveals Loci Implicated In Nucleotide Metabolism, Platelet Activation, And Megakaryocyte Proliferation, R J Longchamps, Mary Feitosa, Mary Wojczynski, Aldi Kraja, Michael Province, Et Al.

2020-Current year OA Pubs

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes …

A Phase 1b Study Of Telisotuzumab Vedotin In Combination With Nivolumab In Patients With Nsclc, D Ross Camidge, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated.

METHODS: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity.

RESULTS: As of January 2020, a total of 37 patients received treatment …

Functional Tic-Like Presentations Differ Strikingly From Provisional Tic Disorder, Amanda L Arbuckle, Emily C Bihun, Bradley L Schlaggar, Kevin J. Black

2020-Current year OA Pubs

No abstract provided.

Protocol For A Proof-Of-Concept Study Evaluating Systematic Quality Improvement With Realtime Event Support (Squires), Arianna Montes De Oca, Thaddeus P. Budelier, Rachel C. Wolfe, Teresa M. Murray-Torres, Melissa Milbrandt, Ryan Guffey, Alex Kronzer, Mara L. Bollini, Brian A. Torres, Bernadette Henrichs, Arbi Ben Abdallah, Sherry L. Mckinnon, Ivan Kangrga, Andrea Reidy, Paul W. Kerby, Michael S. Avidan, Troy S. Wildes

2020-Current year OA Pubs

No abstract provided.

Protocol For The Perioperative Outcome Risk Assessment With Computer Learning Enhancement (Periop Oracle) Randomized Study, Bradley Fritz, Christopher King, Yixin Chen, Alex Kronzer, Joanna Abraham, Arbi Ben Abdallah, Thomas Kannampallil, Thaddeus Budelier, Arianna Montes De Oca, Sherry Mckinnon, Bethany Tellor Pennington, Troy Wildes, Michael Avidan

2020-Current year OA Pubs

No abstract provided.

Decision-Making Factors For An Autologous Stem Cell Transplant For Older Adults With Newly Diagnosed Multiple Myeloma: A Qualitative Analysis, Owais Mian, Martine Puts, Arleigh Mccurdy, Tanya M Wildes, Mark A Fiala, Matthew Kang, Mary Salib, Shabbir Alibhai, Hira Mian

2020-Current year OA Pubs

PURPOSE: A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.

METHODS: A qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.

RESULTS: Eighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with …

A Perspective On Implementation Outcomes And Strategies To Promote The Uptake Of Covid-19 Vaccines, Meagan Pilar, A Rani Elwy, Larissa Lushniak, Grace Huang, Gabriella M Mcloughlin, Cole Hooley, Nisha Nadesan-Reddy, Brittney Sandler, Mosa Moshabela, Olakunle Alonge, Elvin Geng, Enola Proctor

2020-Current year OA Pubs

Recent articles have highlighted the importance of incorporating implementation science concepts into pandemic-related research. However, limited research has been documented to date regarding implementation outcomes that may be unique to COVID-19 vaccinations and how to utilize implementation strategies to address vaccine program-related implementation challenges. To address these gaps, we formed a global COVID-19 implementation workgroup of implementation scientists who met weekly for over a year to review the available literature and learn about ongoing research during the pandemic. We developed a hierarchy to prioritize the applicability of "lessons learned" from the vaccination-related implementation literature. We identified applications of existing implementation …