Medicine and Health Sciences Commons^™

A Novel Piggyback Strategy For Mrna Delivery Exploiting Adenovirus Entry Biology, Myungeun Lee, Paul J Rice-Boucher, Logan Thrasher Collins, Ernst Wagner, Lorenzo Aulisa, Jeffrey Hughes, David T Curiel

2020-Current year OA Pubs

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. Nonetheless, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied "piggyback" transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an …

A Case Study Of Adapting A Health Insurance Decision Intervention From Trial Into Routine Cancer Care, Miles E Charles, Lindsay M Kuroki, Ana A Baumann, Rachel G Tabak, Aimee James, Krista Cooksey, Mary C Politi

2020-Current year OA Pubs

OBJECTIVE: This study adapted Improving Cancer Patients' Insurance Choices (I Can PIC), an intervention to help cancer patients navigate health insurance decisions and care costs. The original intervention improved knowledge and confidence making insurance decisions, however, users felt limited by choices provided in insurance markets. Using decision trees and frameworks to guide adaptations, we modified I Can PIC to focus on using rather than choosing health insurance. The COVID-19 pandemic introduced unforeseen obstacles, prompting changes to study protocols. As a result, we allowed users outside of the study to use I Can PIC (> 1050 guest users) to optimize public …

A Mid-Level Health Manager Intervention To Promote Uptake Of Isoniazid Preventive Therapy Among People With Hiv In Uganda: A Cluster Randomised Trial, Elijah Kakande, Elvin H Geng, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.

METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control …

Plasmonic Fluor-Enhanced Antigen Arrays For High-Throughput, Serological Studies Of Sars-Cov-2, Abraham J Qavi, Chao Wu, Matthew Lloyd, Mohammad Mahabub-Uz Zaman, Jingyi Luan, Claire Ballman, Daisy W Leung, Scott L Crick, Christopher W Farnsworth, Gaya K Amarasinghe

2020-Current year OA Pubs

Serological testing for acute infection or prior exposure is critical for patient management and coordination of public health decisions during outbreaks. Current methods have several limitations, including variable performance, relatively low analytical and clinical sensitivity, and poor detection due to antigenic drift. Serological methods for SARS-CoV-2 detection for the ongoing COVID-19 pandemic suffer from several of these limitations and serves as a reminder of the critical need for new technologies. Here, we describe the use of ultrabright fluorescent reagents, Plasmonic Fluors, coupled with antigen arrays that address a subset of these limitations. We demonstrate its application using patient samples in …

Facilitators Of Multisector Collaboration For Delivering Cancer Control Interventions In Rural Communities: A Descriptive Qualitative Study, Peg Allen, Callie Walsh-Bailey, Jean Hunleth, Bobbi J Carothers, Ross C Brownson

2020-Current year OA Pubs

PURPOSE AND OBJECTIVES: Multisector collaboration is a widely promoted strategy to increase equitable availability, access, and use of healthy foods, safe places for physical activity, social supports, and preventive health care services. Yet fewer studies and resources exist for collaboration among governmental and nongovernmental agencies to address public problems in rural areas, despite an excess burden of risk factors for cancer morbidity and mortality. We aimed to learn about cancer prevention activities and collaboration facilitators among rural informal interagency networks.

EVALUATION METHODS: In 2020, researchers conducted semistructured interviews with staff from rural public health and social services agencies, community health …

Ligand-Based Design, Synthesis, Computational Insights, And In Vitro Studies Of Novel N-(5-Nitrothiazol-2-Yl)-Carboxamido Derivatives As Potent Inhibitors Of Sars-Cov-2 Main Protease, Mohamed Elagawany, Ayman Abo Elmaaty, Ahmed Mostafa, Noura M Abo Shama, Eman Y Santali, Bahaa Elgendy, Ahmed A Al-Karmalawy

2020-Current year OA Pubs

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development of new effective therapeutic interventions for the battle against SARS-CoV-2. A new series of

Changes In Health Care Access During The Covid-19 Pandemic: Estimates Of National Japanese Data, June 2020-October 2021, Yuta Tanoue, Cyrus Ghaznavi, Takayuki Kawashima, Akifumi Eguchi, Daisuke Yoneoka, Shuhei Nomura

2020-Current year OA Pubs

The COVID-19 pandemic has disrupted health care access around the world, both for inpatients and outpatients. We applied a quasi-Poisson regression to national, monthly data on the number of outpatients, number of inpatients, length of average hospital stay, and the number of new hospitalizations from March 2015 to October 2021 to assess how these outcomes changed between June 2020 to October 2021. The number of outpatient visits were lower-than-predicted during the early phases of the pandemic but normalized by the fall of 2021. The number of inpatients and new hospitalizations were lower-than-predicted throughout the pandemic, and deficits in reporting continued …

Association Between The Covid-19 Pandemic And Insurance-Based Disparities In Mortality After Major Surgery Among Us Adults, Laurent G Glance, Andrew W Dick, Ernie Shippey, Patrick J Mccormick, Richard Dutton, Patricia W Stone, Jingjing Shang, Stewart J Lustik, Heather L Lander, Igor Gosev, Karen E Joynt Maddox

2020-Current year OA Pubs

Importance: The COVID-19 pandemic caused significant disruptions in surgical care. Whether these disruptions disproportionately impacted economically disadvantaged individuals is unknown.

Objective: To evaluate the association between the COVID-19 pandemic and mortality after major surgery among patients with Medicaid insurance or without insurance compared with patients with commercial insurance.

Design, Setting, and Participants: This cross-sectional study used data from the Vizient Clinical Database for patients who underwent major surgery at hospitals in the US between January 1, 2018, and May 31, 2020.

Exposures: The hospital proportion of patients with COVID-19 during the first wave of COVID-19 cases between March 1 and …

Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, Sigan L Hartley, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome.

OBJECTIVE/HYPOTHESIS: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome.

METHODS: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged 22-66 years) …

Enabling Hotspot Detection And Public Health Response To The Covid-19 Pandemic, Randi Foraker, Joshua Landman, Ian Lackey, Matthew D Haslam, Alison L Antes, Dennis Goldfarb

2020-Current year OA Pubs

INTRODUCTION: Public-facing maps of COVID-19 cases, hospital admissions, and deaths are commonly displayed at the state, county, and zip code levels, and low case counts are suppressed to protect confidentiality. Public health authorities are tasked with case identification, contact tracing, and canvasing for educational purposes during a pandemic. Given limited resources, authorities would benefit from the ability to tailor their efforts to a particular neighborhood or congregate living facility.

METHODS: We describe the methods of building a real-time visualization of patients with COVID-19-positive tests, which facilitates timely public health response to the pandemic. We developed an interactive street-level visualization that …

A Dual-Center Cohort Study On The Association Between Early Deep Sedation And Clinical Outcomes In Mechanically Ventilated Patients During The Covid-19 Pandemic: The Covid-Sed Study, Robert J Stephens, Erin M Evans, Michael J Pajor, Ryan D Pappal, Haley M Egan, Max Wei, Hunter Hayes, Jason A Morris, Nicholas Becker, Brian W Roberts, Marin H Kollef, Nicholas M Mohr, Brian M Fuller

2020-Current year OA Pubs

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.

STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over …

Assessing Covid-19 Testing Strategies In K-12 Schools In Underserved Populations: Study Protocol For A Cluster-Randomized Trial, Samantha Hayes, Sara Malone, Brittany Bonty, Nancy Mueller, Summer M Reyes, Sydney A Reyes, Christina Evans, Myisha Wilcher-Roberts, Tremayne Watterson, Sewuese Akuse, Jamee Shelley, Grace Yuan, Ian Lackey, Jasmine Prater, Brock Montgomery, Cynthia Williams, Sheretta T Butler-Barnes, Kelly Harris, Charlene Caburnay, Nikole Lobb Dougherty, Jingxia Liu, Albert Lai, Julie Neidich, Stephanie Fritz, Jason G Newland

2020-Current year OA Pubs

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to …

Cardiovascular Tropism And Sequelae Of Sars-Cov-2 Infection, Oleksandr Dmytrenko, Kory J Lavine

2020-Current year OA Pubs

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline …

Transmission Risk Of Covid-19 In High School And College Water Polo, Raymond J Kreienkamp, Christopher J Kreienkamp, Cindy Terrill, Mark E Halstead, Jason G Newland

2020-Current year OA Pubs

BACKGROUND: Concerns that athletes may be at a higher risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has led to reduced participation in sports during the COVID-19 pandemic. We aimed to assess COVID-19 incidence and transmission during the spring 2021 high school and college water polo seasons across the United States.

METHODS: This prospective observational study enrolled 1825 water polo athletes from 54 high schools and 36 colleges. Surveys were sent to coaches throughout the season, and survey data were collected and analyzed.

RESULTS: We identified 17 COVID-19 cases among 1223 high school water polo athletes (1.4%) and …

Host Cell-Intrinsic Innate Immune Recognition Of Sars-Cov-2, Emily A Madden, Michael S Diamond

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged at the end of 2019 and caused the pandemic of coronavirus disease 2019 (COVID-19). Basic and clinical investigations indicate that severe forms of COVID-19 are due in part to dysregulated immune responses to virus infection. The innate immune system is the first line of host defense against most virus infections, with pathogen recognition receptors detecting SARS-CoV-2 RNA and protein components and initiating pro-inflammatory and antiviral responses. Notwithstanding this response, SARS-CoV-2 proteins evade, inhibit, and skew innate immune signaling early in infection. In this review, we highlight the components of cell-based recognition of SARS-CoV-2 …

Virtual Adaptation Of An International Exchange Program In Medical Education, Celia Fung, Nicholas Maxwell, Stephen Powell, Michelle Benassai, Natalia Chunga, Jennifer Corcoran, William Barbosa, Marisabel Lopez, Betsy Hanampa, Melissa Llaiqui-Condori, Victor Delgado-Lazo, Karina Mendoza, Yanet Astete, Martin Flor, Sheyla Palacios, Blanca Valdovinos, Jorge Risco, Isabel Camargo, Ralph Jozefowicz, Karlo J Lizárraga

2020-Current year OA Pubs

Medical education has drastically transformed during the COVID-19 pandemic. Measures such as adopting telemedicine visits, minimizing the number of trainees on service, discontinuing external rotations, and converting in-person to online didactics have been broadly and swiftly implemented. While these innovations have promoted greater interconnectivity amongst institutions and made continuing medical education possible, international exchange programs in medical education are still largely disrupted. In response to the changing guidelines and restrictions necessitated by the COVID-19 pandemic, the authors used Kern's six-step approach to design and implement a virtual curriculum to replace the in-person activities of the 2020-2021 Neurology Peru-Rochester exchange program …

The First 20 Months Of The Covid-19 Pandemic: Mortality, Intubation And Icu Rates Among 104,590 Patients Hospitalized At 21 United States Health Systems, Michael C. Fiore, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.

STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR …

Barriers To Symptom Management Care Pathway Implementation In Pediatric Cancer, L Lee Dupuis, Allison Grimes, Emily Vettese, Lisa M Klesges, Lillian Sung

2020-Current year OA Pubs

BACKGROUND: Objectives were to describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation.

METHODS: We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators prior to randomization to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Michael L Alosco, Daniel S Marcus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Association Of Clinical Factors And Recent Anticancer Therapy With Covid-19 Severity Among Patients With Cancer: A Report From The Covid-19 And Cancer Consortium, P Grivas, K E Stockerl-Goldstein, A Y Zhou, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). …

Risk Factors Associated With Physician Trainee Concern Over Missed Educational Opportunities During The Covid-19 Pandemic, Sunny S Lou, Charles W Goss, Bradley A Evanoff, Jennifer G Duncan, Thomas Kannampallil

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic resulted in a transformation of clinical care practices to protect both patients and providers. These changes led to a decrease in patient volume, impacting physician trainee education due to lost clinical and didactic opportunities. We measured the prevalence of trainee concern over missed educational opportunities and investigated the risk factors leading to such concerns.

METHODS: All residents and fellows at a large academic medical center were invited to participate in a web-based survey in May of 2020. Participants responded to questions regarding demographic characteristics, specialty, primary assigned responsibility during the previous 2 weeks (clinical, education, or …

A Risk Assessment Tool For Resumption Of Research Activities During The Covid-19 Pandemic For Field Trials In Low Resource Settings, Suzanne M Simkovich, Victor G Davila-Roman, Lisa De Las Fuentes, Et Al.

2020-Current year OA Pubs

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk.

OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial conducted in rural, low-resource settings, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize the integrity of reseach aims while minimizing infection risk based on the latest scientific understanding of the virus.

METHODS: We …

The Clinical Course Of Coronavirus Disease 2019 In A Us Hospital System: A Multistate Analysis, Aaloke Mody, Patrick G Lyons, Cristina Vazquez Guillamet, Andrew Michelson, Sean Yu, Angella Sandra Namwase, Pratik Sinha, William G Powderly, Keith Woeltje, Elvin H Geng

2020-Current year OA Pubs

There are limited data on longitudinal outcomes for coronavirus disease 2019 (COVID-19) hospitalizations that account for transitions between clinical states over time. Using electronic health record data from a hospital network in the St. Louis, Missouri, region, we performed multistate analyses to examine longitudinal transitions and outcomes among hospitalized adults with laboratory-confirmed COVID-19 with respect to 15 mutually exclusive clinical states. Between March 15 and July 25, 2020, a total of 1,577 patients in the network were hospitalized with COVID-19 (49.9% male; median age, 63 years (interquartile range, 50-75); 58.8% Black). Overall, 34.1% (95% confidence interval (CI): 26.4, 41.8) had …

A Timely Call To Arms: Covid-19, The Circadian Clock, And Critical Care, Jeffrey Haspel, Minjee Kim, Phyllis Zee, Tanja Schwarzmeier, Sara Montagnese, Satchidananda Panda, Adriana Albani, Martha Merrow

2020-Current year OA Pubs

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on …