Medicine and Health Sciences Commons^™

Academic Medical Center Clinical Research Professional Workforce: Part 2 - Issues In Staff Onboarding And Professional Development, Jacqueline M Knapke, Michelle Jenkerson, Peg Tsao, Stephanie Freel, Jessica Fritter, Shirley L Helm, Penelope Jester, H Robert Kolb, Angela Mendell, Megan Petty, Carolynn T Jones

2020-Current year OA Pubs

Background: Defining key barriers to the development of a well-trained clinical research professional (CRP) workforce is an essential first step in identifying solutions for successful CRP onboarding, training, and competency development, which will enhance quality across the clinical and translational research enterprise. This study aimed to summarize barriers and best practices at academic medical centers related to effective CRP onboarding, training, professional development, identify challenges with the assessment of and mentoring for CRP competency growth, and describe opportunities to improve training and professionalization for the CRP career pathway.

Materials/Methods: Qualitative data from a series of Un-Meeting breakout sessions and open-text …

Patient Clinical Documentation In Telehealth Environment: Are We Collecting Appropriate And Sufficient Information For Best Practice?, Shannon H. Houser, Cathy A. Flite, Susan L. Foster, Thomas J. Hunt, Angela Morey, Miland N. Palmer, Jennifer Peterson, Roberta Damez Pope, Linda Sorensen

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, the use of telehealth for patient visits grew rapidly and served an important role as a valuable and necessary resource. Although clinical documentation is critical for telehealth patient visits, there is limited information about how healthcare facilities manage telehealth patient visit documentation, technology used for telehealth visits, and challenges encountered with telehealth patient visit documentation. This study aimed to assess the use of telehealth during the pandemic, the quality of clinical documentation in telehealth practice and to identify challenges and issues encountered with telehealth patient visits in order to develop a strategy for best practices …

Hydroxychloroquine/Chloroquine For The Treatment Of Hospitalized Patients With Covid-19: An Individual Participant Data Meta-Analysis, Leon Di Stefano, Jane A. O'Halloran, Adriana M. Rauseo, Et Al

2020-Current year OA Pubs

BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 …

The Future Of Ad Clinical Trials With The Advent Of Anti-Amyloid Therapies: An Ctad Task Force Report, J Delrieu, R J Bateman, J Touchon, M Sabbagh, J Cummings

2020-Current year OA Pubs

BACKGROUND: Aducanumab (ADUHELMTM) was approved for the treatment of Alzheimer's disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. …

Tourette Syndrome Research Highlights From 2021, Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Marinette Debes, Natalia Szejko, Keisuke Ueda, Kevin J. Black

2020-Current year OA Pubs

We summarize selected research reports from 2021 relevant to Tourette syndrome that the authors consider most important or interesting. The authors welcome article suggestions and thoughtful feedback from readers.

Chronic Stroke Sensorimotor Impairment Is Related To Smaller Hippocampal Volumes: An Enigma Analysis, Artemis Zavaliangos-Petropulu, Keith Lohse, Et Al

2020-Current year OA Pubs

No abstract provided.

Voting Behavior During Fda Medical Device Advisory Committee Panel Meetings, Amanda Maisel-Campbell, Daniel I Schlessinger, Arianna F. Yanes, Emir Veledar, Kelly A. Reynolds, Sarah A. Ibrahim, Bianca Y. Kang, Noor Anvery, Emily Poon, Murad Alam

2020-Current year OA Pubs

OBJECTIVES: During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations.

METHODS: This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to …

Comparative Analysis Of Dcas9-Vp64 Variants And Multiplexed Guide Rnas Mediating Crispr Activation, Kohei Omachi, Jeffrey H. Miner

2020-Current year OA Pubs

CRISPR/Cas9-mediated transcriptional activation (CRISPRa) is a powerful tool for investigating complex biological phenomena. Although CRISPRa approaches based on the VP64 transcriptional activator have been widely studied in both cultured cells and in animal models and exhibit great versatility for various cell types and developmental stages in vivo, different dCas9-VP64 versions have not been rigorously compared. Here, we compared different dCas9-VP64 constructs in identical contexts, including the cell lines used and the transfection conditions, for their ability to activate endogenous and exogenous genes. Moreover, we investigated the optimal approach for VP64 addition to VP64- and p300-based constructs. We found that MS2-MCP-scaffolded …

Preeclampsia Is Associated With Reduced Isg15 Levels Impairing Extravillous Trophoblast Invasion, Asli Ozmen, Anthony O Odibo, Et Al

2020-Current year OA Pubs

Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls. This led us to hypothesize that competitive binding of these cytokines to the gp130 impairs extravillous trophoblast (EVT) differentiation, proliferation and/or invasion. Using global microarray analysis, the current study identified inhibition of interferon-stimulated gene 15 (

Internalization Of Appearance Ideals And Not Religiosity Indirectly Impacts The Relationship Between Acculturation And Disordered Eating Risk In South And Southeast Asian Women Living In The United States, Sonakshi Negi, Erik M Benau, Megan Strowger, Anne Claire Grammer, C Alix Timko

2020-Current year OA Pubs

Objective: Studies that examine disordered eating in samples of Asian individuals living in the United States frequently combine all individuals of Asian descent into a single group, which can obscure important differences between groups and their experiences of acculturation. The goal of the present study was to establish the relation of acculturation, internalization of appearance ideals, and religiosity as predicting body dissatisfaction and disordered eating in women of South and Southeast Asian (SSEA) descent.

Method: Women of SSEA descent (

Results: Direct paths from acculturation to both body dissatisfaction and disordered eating were not significant. Thin ideal internalization completely accounted …

Combining Empirical Knowledge, In Silico Molecular Docking And Admet Profiling To Identify Therapeutic Phytochemicals From Brucea Antidysentrica For Acute Myeloid Leukemia, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Doheon Lee

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is one of the deadly cancers. Chemotherapy is the first-line treatment and the only curative intervention is stem cell transplantation which are intolerable for aged and comorbid patients. Therefore, finding complementary treatment is still an active research area. For this, empirical knowledge driven search for therapeutic agents have been carried out by long and arduous wet lab processes. Nonetheless, currently there is an accumulated bioinformatics data about natural products that enabled the use of efficient and cost effective in silico methods to find drug candidates. In this work, therefore, we set out to computationally investigate the …

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 …

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 …

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 …

Polypill For Atherosclerotic Cardiovascular Disease Prevention In Haiti: Eligibility Estimates In A Low-Income Country, Lily D Yan, Vanessa Rouzier, Jean Lookens Pierre, Eliezer Dade, Rodney Sufra, Mark D Huffman, Alexandra Apollon, Stephano St Preux, Miranda Metz, Shalom Sabwa, Béatrice Morisset, Marie Deschamps, Jean W Pape, Margaret L Mcnairy

2020-Current year OA Pubs

BACKGROUND: Multidrug therapy is a World Health Organization "best buy" for the prevention and control of noncommunicable diseases. CVD polypills, including ≥2 blood pressure medications, and a statin with or without aspirin, are an effective, scalable strategy to close the treatment gap that exists in many low- and middle-income countries, including Haiti. We estimated the number of Haitian adults eligible for an atherosclerotic CVD (ASCVD) polypill, and the number of potentially preventable CVD events if polypills were implemented nationally.

METHODS: We used cross-sectional data from the Haiti CVD Cohort, a population-based cohort of 3,005 adults ≥18 years in Port-au-Prince, to …

The Human Myocardium Harbors A Population Of Naive B-Cells With A Distinctive Gene Expression Signature Conserved Across Species, Kevin C Bermea, Nicolas Kostelecky, Sylvie T Rousseau, Chieh-Yu Lin, Luigi Adamo

2020-Current year OA Pubs

INTRODUCTION: Cardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.

METHODS: We performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells …

Transient Equilibrium Determination Of Dopamine D2/D3 Receptor Densities And Affinities In Brain, Jenny-Ann Phan, Dean F Wong, Natalie H S Chang, Yoshitaka Kumakura, William R Bauer, Albert Gjedde

2020-Current year OA Pubs

Long-term alteration of dopaminergic neurotransmission is known to modulate the D

Lack Of Pathogen Identification Influencing Antibiotic De-Escalation In Hospital-Acquired Pneumonia, Matthew C Bittmann, Scott T Micek, Marin H Kollef

2020-Current year OA Pubs

No abstract provided.

Coronavirus Disease 2019 (Covid-19) Vaccine Breakthrough Infections Among Healthcare Personnel, December 2020-April 2021, Katelin B Nickel, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19) vaccine effectiveness in the early months of vaccine availability was high among healthcare personnel (HCP) at 88.3% for 2-doses. Among those testing positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), those with breakthrough infection after vaccination were more likely to have had a non-work-related SARS-CoV-2 exposure compared to unvaccinated HCP.

All-Cause And In-Hospital Mortality After Aspirin Use In Patients Hospitalized With Covid-19: A Systematic Review And Meta-Analysis, Nischit Baral, Joshua D Mitchell, Pramod K Savarapu, Maxwell Akanbi, Bandana Acharya, Soumya Kambalapalli, Amith Seri, Krishna P Bashyal, Arvind Kunadi, Niranjan Ojha, Annabelle Santos Volgman, Tripti Gupta, Timir K Paul

2020-Current year OA Pubs

BACKGROUND: With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations.

MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects …

Psychiatric Comorbidity And Psychosocial Stressors Among People Initiating Hiv Care In Cameroon, Angela M. Parcesepe, Lindsey M. Filiatreau, Peter Vanes Ebasone, Anastase Dzudie, Brian W. Pence, Milton Wainberg, Marcel Yotebieng, Kathryn Anastos, Eric Pefura-Yone, Denis Nsame, Rogers Ajeh, Denis Nash

2020-Current year OA Pubs

BACKGROUND: Psychiatric comorbidity, the presence of two or more mental health disorders, has been associated with suboptimal HIV treatment outcomes. Little is known about the prevalence of psychiatric comorbidity among people with HIV (PWH) in sub-Saharan Africa.

METHODS: We conducted interviews with PWH initiating HIV care in Cameroon between June 2019 and March 2020. Depression, anxiety, post-traumatic stress disorder (PTSD), and harmful drinking were dichotomized to represent those with and without symptoms of each. Psychiatric comorbidity was defined as having symptoms of two or more disorders assessed. Moderate or severe household hunger, high anticipatory HIV-related stigma, low social support, and …

Antibodies In Healthcare Personnel Following Severe Acute Respiratory Syndrome Coronavirus Virus 2 (Sars-Cov-2) Infection, Rachel E Bosserman, Christopher W Farnsworth, Caroline A O'Neil, Candice Cass, Daniel Park, Claire Ballman, Meghan A Wallace, Emily Struttmann, Henry Stewart, Olivia Arter, Kate Peacock, Victoria J Fraser, Philip J Budge, Margaret A Olsen, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters

2020-Current year OA Pubs

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14-28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70-180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.

Reconstructing Neural Circuits Using Multiresolution Correlated Light And Electron Microscopy, Karl Friedrichsen, Pratyush Ramakrishna, Jen-Chun Hsiang, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

Correlated light and electron microscopy (CLEM) can be used to combine functional and molecular characterizations of neurons with detailed anatomical maps of their synaptic organization. Here we describe a multiresolution approach to CLEM (mrCLEM) that efficiently targets electron microscopy (EM) imaging to optically characterized cells while maintaining optimal tissue preparation for high-throughput EM reconstruction. This approach hinges on the ease with which arrays of sections collected on a solid substrate can be repeatedly imaged at different scales using scanning electron microscopy. We match this multiresolution EM imaging with multiresolution confocal mapping of the aldehyde-fixed tissue. Features visible in lower resolution …

Endogenous Opioid Systems Alterations In Pain And Opioid Use Disorder, Jessica A Higginbotham, Tamara Markovic, Nicolas Massaly, Jose A Morón

2020-Current year OA Pubs

Decades of research advances have established a central role for endogenous opioid systems in regulating reward processing, mood, motivation, learning and memory, gastrointestinal function, and pain relief. Endogenous opioid systems are present ubiquitously throughout the central and peripheral nervous system. They are composed of four families, namely the μ (MOPR), κ (KOPR), δ (DOPR), and nociceptin/orphanin FQ (NOPR) opioid receptors systems. These receptors signal through the action of their endogenous opioid peptides β-endorphins, dynorphins, enkephalins, and nociceptins, respectfully, to maintain homeostasis under normal physiological states. Due to their prominent role in pain regulation, exogenous opioids-primarily targeting the MOPR, have been …

Apoe Mediated Neuroinflammation And Neurodegeneration In Alzheimer's Disease, Samira Parhizkar, David M Holtzman

2020-Current year OA Pubs

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in …

Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al.

2020-Current year OA Pubs

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO