Medicine and Health Sciences Commons^™

Severity Of Respiratory Syncytial Virus Vs Covid-19 And Influenza Among Hospitalized Us Adults, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.

OBJECTIVE: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively …

The Disordered N-Terminal Tail Of Sars-Cov-2 Nucleocapsid Protein Forms A Dynamic Complex With Rna, Jasmine Cubuk, Jhullian J Alston, J Jeremías Incicco, Alex S Holehouse, Kathleen B Hall, Melissa D Stuchell-Brereton, Andrea Soranno

2020-Current year OA Pubs

The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA binding domain (RBD) and its flanking disordered N-terminal domain (NTD) tail, using single-molecule Förster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific …

Reports Of Covid-19 Vaccine Adverse Events In Predominantly Republican Vs Democratic States, David A Asch, Chongliang Luo, Yong Chen

2020-Current year OA Pubs

IMPORTANCE: Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored.

OBJECTIVE: To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican …

Mucosal Vaccine-Induced Cross-Reactive Cd8+ T Cells Protect Against Sars-Cov-2 Xbb.1.5 Respiratory Tract Infection, Baoling Ying, Tamarand L Darling, Pritesh Desai, Chieh-Yu Liang, Igor P Dmitriev, Nadia Soudani, Traci Bricker, Elena A Kashentseva, Houda Harastani, Saravanan Raju, Meizi Liu, Aaron G Schmidt, David T Curiel, Adrianus C M Boon, Michael S Diamond

2020-Current year OA Pubs

A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8

Description Of Cryptococcosis Following Sars-Cov-2 Infection: A Disease Survey Through The Mycosis Study Group Education And Research Consortium (Msg-19), Jeremey Walker, Andrej Spec, Adriana M Rauseo, Et Al.

2020-Current year OA Pubs

BACKGROUND: Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes.

METHODS: We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap …

Immunoglobulin Replacement Products Protect Against Sars-Cov-2 Infection In Vivo Despite Poor Neutralizing Activity, Ofer Zimmerman, Alexa Michelle Altman Doss, Baoling Ying, Chieh-Yu Liang, Samantha R. Mackin, Hannah G. Davis-Adams, Lucas J. Adams, Laura A. Vanblargan, Rita E. Chen, Suzanne M. Scheaffer, Pritesh Desai, Saravanan Raju, Tarisa L. Mantia, Caitlin C. O'Shaughnessy, Jennifer Marie Monroy, H. James Wedner, Christopher J. Rigell, Andrew L. Kau, Tiffany Biason Dy, Zhen Ren, Jackson S. Turner, Jane A. O'Halloran, Rachel M. Presti, Peggy L. Kendall, Daved H. Fremont, Ali H. Ellebedy, Michael S Diamond

2020-Current year OA Pubs

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors …

Immune Response To Sars-Cov-2 Variants After Immunization With Different Vaccines In Mexico, Erika Garay, Sean P J Whelan, Rebecca M Dubois, Sara M O'Rourke, Angel Eduardo Salgado-Escobar, José Esteban Muñoz-Medina, Carlos F Arias, Susana López

2020-Current year OA Pubs

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior …

Mucosal Boosting Enhances Vaccine Protection Against Sars-Cov-2 In Macaques, Katherine Mcmahan, Adrianus C M Boon, Et Al.

2020-Current year OA Pubs

A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants

Leveraging Mhealth To Mitigate The Impact Of Covid-19 In Black American Communities: Qualitative Analysis, Kelly M Harris, Tilicia Mayo Gamble, Madelyn G Yoo, Lindsay A Spell, Timira N Minor, Holly Jones, Donald Lynch

2020-Current year OA Pubs

BACKGROUND: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations.

OBJECTIVE: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, …

A Broadly Reactive Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Spike Confers Fc-Mediated Protection, Lucas J Adams, Laura A Vanblargan, Zhuoming Liu, Pavlo Gilchuk, Haiyan Zhao, Rita E Chen, Saravanan Raju, Zhenlu Chong, Bradley M Whitener, Swathi Shrihari, Prashant N Jethva, Michael L Gross, James E Crowe Jr., Sean P J Whelan, Michael S Diamond, Daved H Fremont

2020-Current year OA Pubs

Most neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells. One neutralizing NTD mAb, SARS2-57, protects K18-hACE2 mice against SARS-CoV-2 infection in an Fc-dependent manner. Structural analysis demonstrates that SARS2-57 engages an antigenic supersite that is remodeled by deletions common to emerging variants. In neutralization escape studies with SARS2-57, this NTD site accumulates mutations, including …

A Single C-Terminal Residue Controls Sars-Cov-2 Spike Trafficking And Incorporation Into Vlps, Debajit Dey, Enya Qing, Yanan He, Yihong Chen, Benjamin Jennings, Whitaker Cohn, Suruchi Singh, Lokesh Gakhar, Nicholas J Schnicker, Brian G Pierce, Julian P Whitelegge, Balraj Doray, John Orban, Tom Gallagher, S Saif Hasan

2020-Current year OA Pubs

The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation …

Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry

2020-Current year OA Pubs

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean …

Obesity And Outcomes Of Kawasaki Disease And Covid-19-Related Multisystem Inflammatory Syndrome In Children, Michael Khoury, William B Orr, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.

OBJECTIVE: To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with …

Comparison Of Joint Mobilization And Movement Pattern Training For Patients With Hip-Related Groin Pain: A Pilot Randomized Clinical Trial, Marcie Harris-Hayes, Patricia Zorn, Karen Steger-May, Megan M Burgess, Rebecca D Demargel, Suzanne Kuebler, John Clohisy, Simon Haroutounian

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to assess the feasibility of completing a randomized clinical trial (RCT) and examine the preliminary effects of 2 interventions for hip-related groin pain (HRGP).

METHODS: In this pilot RCT, patients with HRGP, who were 18 to 40 years old, were randomized (1:1 ratio) to a joint mobilization (JtMob) group or a movement pattern training (MoveTrain) group. Both treatments included 10 supervised sessions and a home exercise program. The goal of JtMob was to reduce pain and improve mobility through peripherally and centrally mediated pain mechanisms. The key element was physical therapist-provided JtMob. The …

Humoral Immune Response To Covid-19 Mrna Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Ofatumumab, Amit Bar-Or, Rany Aburashed, Angel R Chinea, Barry A Hendin, Elisabeth Lucassen, Xiangyi Meng, James Stankiewicz, Mark J Tullman, Anne H Cross

2020-Current year OA Pubs

BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab.

METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined …

Elevated Level Of Circulating But Not Urine S100a8/A9 Identifies Poor Covid-19 Outcomes, Leah Mellett, Gaya Amarasinghe, Christopher W Farnsworth, Shabaana A Khader

2020-Current year OA Pubs

The alarmin calprotectin (S100A8/A9) is thought to drive a cytokine storm, a hallmark of severe COVID-19. Recent studies report circulating S100A8/A9 levels can distinguish COVID-19 severity but have only been conducted in non-U.S. cohorts and mainly focus on serum S100A8/A9 levels. Thus, we quantified S100A8/A9 in serum and urine samples from a hospital cohort in St. Louis, Missouri, to expand the understanding of S100A8/A9 as a prognostic biomarker for COVID-19. Elevated S100A8/A9 serum levels were observed in ICU patients (

The Impact Of Helminth-Induced Immunity On Infection With Bacteria Or Viruses, Hong Chen, Zengguo Cao, Mingyuan Liu, Michael S Diamond, Xuemin Jin

2020-Current year OA Pubs

Different human and animal pathogens trigger distinct immune responses in their hosts. The infection of bacteria or viruses can trigger type I pro-inflammatory immune responses (e.g., IFN-γ, TNF-α, T

Was Covid-19 Associated With Worsening Inequities In Stroke Treatment And Outcomes?, Laurent G Glance, Curtis G Benesch, Karen E Joynt Maddox, Matthew T Bender, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Jacob W Nadler, Christopher Galton, Andrew W Dick

2020-Current year OA Pubs

Background COVID-19 stressed hospitals and may have disproportionately affected the stroke outcomes and treatment of Black and Hispanic individuals. Methods and Results This retrospective study used 100% Medicare Provider Analysis and Review file data from between 2016 and 2020. We used interrupted time series analyses to examine whether the COVID-19 pandemic exacerbated disparities in stroke outcomes and reperfusion therapy. Among 1 142 560 hospitalizations for acute ischemic strokes, 90 912 (8.0%) were Hispanic individuals; 162 752 (14.2%) were non-Hispanic Black individuals; and 888 896 (77.8%) were non-Hispanic White individuals. The adjusted odds of mortality increased by 51% (adjusted odds ratio …

Antibody Response To Sars-Cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: A Bruton's Tyrosine Kinase Inhibitor, Amit Bar-Or, Anne H Cross, Anthony L Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban

2020-Current year OA Pubs

BACKGROUND: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton's tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS).

OBJECTIVE: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349).

METHODS: A

RESULTS: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient's antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, …

Introduction To A Compendium Of Strategies To Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates, Deborah S Yokoe, Hilary M Babcock, Erik R Dubberke, Jonas Marschall, Et Al.

2020-Current year OA Pubs

Since the initial publication of

The Impact Of Adding Cost Information To A Conversation Aid To Support Shared Decision Making About Low-Risk Prostate Cancer Treatment: Results Of A Stepped-Wedge Cluster Randomised Trial, Mary C Politi, Rachel C Forcino, Katelyn Parrish, Marie-Anne Durand, A James O'Malley, Rachel Moses, Krista Cooksey, Glyn Elwyn

2020-Current year OA Pubs

BACKGROUND: Decision aids help patients consider the benefits and drawbacks of care options but rarely include cost information. We assessed the impact of a conversation-based decision aid containing information about low-risk prostate cancer management options and their relative costs.

METHODS: We conducted a stepped-wedge cluster randomised trial in outpatient urology practices within a US-based academic medical center. We randomised five clinicians to four intervention sequences and enroled patients newly diagnosed with low-risk prostate cancer. Primary patient-reported outcomes collected postvisit included the frequency of cost conversations and referrals to address costs. Other patient-reported outcomes included: decisional conflict postvisit and at 3 …

Knowledge, Beliefs, And Practices Related To Coronavirus Disease 2019 (Covid-19) Infection And Vaccination In Healthcare Personnel Working At Nonacute Care Facilities, Armaghan-E-Rehman Mansoor, Caroline A O'Neil, David Mcdonald, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities.

DESIGN: Anonymous survey.

SETTING: Three non-acute-care facilities in St. Louis, Missouri.

PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles.

METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19.

RESULTS: Nearly all respondents …

Molecular Imaging Of Ace2 Expression In Infectious Disease And Cancer, Zhiyao Li, Abbie Hasson, Lasya Daggumati, Hanwen Zhang, Daniel L J Thorek

2020-Current year OA Pubs

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that plays a critical role in the pathogenesis of SARS-CoV-2 infection. Through the use of ligands engineered for the receptor, ACE2 imaging has emerged as a valuable tool for preclinical and clinical research. These can be used to visualize the expression and distribution of ACE2 in tissues and cells. A variety of techniques including optical, magnetic resonance, and nuclear medicine contrast agents have been developed and employed in the preclinical setting. Positron-emitting radiotracers for highly sensitive and quantitative tomography have also been translated in the context of SARS-CoV-2-infected and control patients. Together …

Adding Pharmacist-Led Home Blood Pressure Telemonitoring To Usual Care For Blood Pressure Control: A Systematic Review And Meta-Analysis, Nischit Baral, Annabelle Santos Volgman, Amith Seri, Vijaya Chelikani, Sakiru Isa, Sri L P Javvadi, Timir K Paul, Joshua D Mitchell

2020-Current year OA Pubs

Health systems have been quickly adopting telemedicine throughout the United States, especially since the onset of the COVID-19 pandemic. However, there are limited data on whether adding pharmacist-led home blood pressure (BP) telemonitoring to office-based usual care improves BP. We searched PubMed/MEDLINE and Embase for randomized controlled trials from January 2000 until April 2022, comparing studies on pharmacist-led home BP telemonitoring with usual care. Six randomized controlled trials, including 1,550 participants, satisfied the inclusion criteria. There were 774 participants in the pharmacist-led telemonitoring group and 776 in the usual care group. The addition of pharmacist-led telemonitoring to usual care was …

Postacute Sequelae Of Covid-19 At 2 Years, Benjamin Bowe, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the …

Neutralization, Effector Function And Immune Imprinting Of Omicron Variants, Amin Addetia, James Brett Case, Suzanne M Scheaffer, Bradley Whitener, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain

Safety And Efficacy Of Riluzole In Acute Spinal Cord Injury Study (Riscis): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial, Michael G Fehlings, Wilson Z Ray, Et Al.

2020-Current year OA Pubs

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

Comparison Of Bivalent And Monovalent Sars-Cov-2 Variant Vaccines: The Phase 2 Randomized Open-Label Covail Trial, Angela R Branche, Rachel M Presti, Et Al.

2020-Current year OA Pubs

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID

Fidelity And Adherence To A Liquefied Petroleum Gas Stove And Fuel Intervention: The Multi-Country Household Air Pollution Intervention Network (Hapin) Trial, Kendra N Williams, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Reducing household air pollution (HAP) to levels associated with health benefits requires nearly exclusive use of clean cooking fuels and abandonment of traditional biomass fuels.

METHODS: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3,195 pregnant women in Guatemala, India, Peru, and Rwanda to receive a liquefied petroleum gas (LPG) stove intervention (n = 1,590), with controls expected to continue cooking with biomass fuels (n = 1,605). We assessed fidelity to intervention implementation and participant adherence to the intervention starting in pregnancy through the infant's first birthday using fuel delivery and repair records, surveys, observations, and temperature-logging stove …

Evaluation Of Plasma Biomarkers To Predict Major Adverse Kidney Events In Hospitalized Patients With Covid-19, Steven Menez, Madhurima Kaushal, Sanjay Jain, Et Al.

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers.

EXPOSURE: Twenty-six plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization.

OUTCOME: MAKE, defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days.

ANALYTICAL APPROACH: Cox proportional hazards regression …