Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics.

Research Question: Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status?

Study Design And Methods: This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data.

Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients.

Background: Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown.

Methods: This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021.

Change in effectiveness of sotrovimab for preventing hospitalization and mortality for at-risk COVID-19 outpatients during an Omicron BA.1 and BA.1.1-predominant phase.

Objectives: Sotrovimab effectively prevented progression to severe disease and mortality following infection with pre-Omicron SARS-CoV-2 variants. We sought to determine whether sotrovimab is similarly effective against SARS-CoV-2 Omicron variant infection.

Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021, to March 10, 2022, using electronic health records from a statewide health system.

Energy intake estimation using a novel wearable sensor and food images in a laboratory (pseudo-free-living) meal setting: quantification and contribution of sources of error.

Objectives: Dietary assessment methods not relying on self-report are needed. The Automatic Ingestion Monitor 2 (AIM-2) combines a wearable camera that captures food images with sensors that detect food intake. We compared energy intake (EI) estimates of meals derived from AIM-2 chewing sensor signals, AIM-2 images, and an internet-based diet diary, with researcher conducted weighed food records (WFR) as the gold standard.

Fat Soluble Vitamin Assessment and Supplementation in Cholestasis.

Malnutrition in children with chronic cholestasis is a prevalent issue and a major risk factor for adverse outcomes. Fat soluble vitamin (FSV) deficiency is an integral feature of cholestatic disease in children, often occurring within the first months of life in those with neonatal cholestasis and malnutrition. This review focuses on FSVs in cholestasis, with particular emphasis on a practical approach to surveillance and supplementation that includes approaches that account for differing local resources.

Improvement of Methodology for Manual Energy Intake Estimation From Passive Capture Devices.

Objective: To describe best practices for manual nutritional analyses of data from passive capture wearable devices in free-living conditions.

Method: 18 participants (10 female) with a mean age of 45 ± 10 years and mean BMI of 34.2 ± 4.

Exploring the feasibility of validating early developmental screening tools for American Indian and Alaska Native children.

Screening children from birth through age 5 is critical to early identification of challenges and referral to intervention to support optimal development. Screening of American Indian and Alaska Native (AIAN) children lags behind that of other children, partly due to the lack of screening tools validated for this population. This study tested the feasibility of an online data collection strategy for use in a future study of the validity of existing screening instruments for AIAN children.

Real-World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) patients, is also effective in preventing the progression of severe disease and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection.

Methods: In an observational cohort study of nonhospitalized adult patients with SARS-CoV-2 infection, 1 October 2021-11 December 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data, we used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization.

Sex Differences in RANTES (CCL5) in Patients With Intermediate Age-Related Macular Degeneration (AMD) and Controls With no AMD.

Purpose: To determine if there are sex differences in levels of regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with intermediate age-related macular degeneration (iAMD) and in controls with no AMD.

Methods: Patients with iAMD and controls defined by multi-modal imaging were recruited into a Colorado AMD registry. Plasma levels of the chemokine RANTES were measured using a multiplex assay.

Clinical research reactivation during the COVID-19 pandemic: An academic center process and lessons for the future.

Background: Clinical research is a central mission of the University of Colorado Anschutz Medical Campus (CU-Anschutz). On March 18, 2020, due to rising COVID-19 rates and personal protective equipment (PPE) shortages, an emergency approval process for critical research essential to the care and safety of patients, including COVID-19 trials, was enacted. All other clinical research studies requiring face-to-face visits were placed on hold to protect participant and staff safety.

Plasma C-C Chemokine Concentrations in Intermediate Age-Related Macular Degeneration.

To determine the relationship between plasma concentrations of the C-C chemokines CCL2, CCL3, CCL4, and CCL5 and intermediate age-related macular degeneration (iAMD) patients compared with control inidividuals to further define the inflammatory pathways associated with age-related macular degeneration. The concentrations of CCL2, CCL3, CCL4, and CCL5 were measured using multiplex assays in plasma collected from 210 patients with iAMD and 102 control individuals with no macular degeneration as defined by multi-modal imaging. Non-inflammatory data included in the analysis were: age, sex, family history of AMD, history of smoking, body mass index, presence of reticular pseudo-drusen and cardiovascular disease.

A stakeholder engagement method navigator webtool for clinical and translational science.

Stakeholder engagement is increasingly expected by funders and valued by researchers in clinical and translational science, yet many researchers lack access to expert consultation or training in selecting appropriate stakeholder engagement methods. We describe the development of a novel Stakeholder Engagement Navigator webtool. We conducted an environmental scan and literature review, along with investigator interviews, surveys, and engagement expert facilitated group discussion.

A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial.

Fostering innovation at Academic Medical Centers: The Case of University of Colorado Anschutz Medical Campus.

Commercializing biomedical discoveries is a challenging process for many reasons. However, Academic Medical Centers (AMC) that have teaching, patient care, research, and service engrained in their mission are well poised to host these discoveries. These academic discoveries can lead to improvement in patient health and economic development if supported to cross the "valley of death" through institutional assistance, by providing guidance, gap funding and product development expertise.

It should not require a pandemic to make community engagement in research leadership essential, not optional.

Efforts to move community engagement in research from marginalized to mainstream include the NIH requiring community engagement programs in all Clinical and Translational Science Awards (CTSAs). However, the COVID-19 pandemic has exposed how little these efforts have changed the dominant culture of clinical research. When faced with the urgent need to generate knowledge about prevention and treatment of the novel coronavirus, researchers largely neglected to involve community stakeholders early in the research process.

Systems Analysis of Gut Microbiome Influence on Metabolic Disease in HIV-Positive and High-Risk Populations.

Poor metabolic health, characterized by insulin resistance and dyslipidemia, is higher in people living with HIV and has been linked with inflammation, antiretroviral therapy (ART) drugs, and ART-associated lipodystrophy (LD). Metabolic disease is associated with gut microbiome composition outside the context of HIV but has not been deeply explored in HIV infection or in high-risk men who have sex with men (HR-MSM), who have a highly altered gut microbiome composition. Furthermore, the contribution of increased bacterial translocation and associated systemic inflammation that has been described in HIV-positive and HR-MSM individuals has not been explored.

Early Childhood Caries in Indigenous Communities.

The oral health of Indigenous children of Canada (First Nations, Inuit, and Métis) and the United States (American Indian and Alaska native) is a major child health disparity when compared with the general population of both countries. Early childhood caries (ECC) occurs in Indigenous children at an earlier age, with a higher prevalence, and at much greater severity than in the general population. ECC results in adverse oral health, affecting childhood health and well-being, and may result in high rates of costly surgical treatment under general anesthesia.

I-Corps@NCATS trains clinical and translational science teams to accelerate translation of research innovations into practice.

Introduction: A key barrier to translation of biomedical research discoveries is a lack of understanding among scientists regarding the complexity and process of implementation. To address this challenge, the National Science Foundation's Innovation Corps™ (I-Corps™) program trains researchers in entrepreneurship. We report results from the implementation of an I-Corps™ training program aimed at biomedical scientists from institutions funded by the National Center for Advancing Translational Sciences (NCATS).

Applying Clinical Decision Support Design Best Practices With the Practical Robust Implementation and Sustainability Model Versus Reliance on Commercially Available Clinical Decision Support Tools: Randomized Controlled Trial.

Background: Limited consideration of clinical decision support (CDS) design best practices, such as a user-centered design, is often cited as a key barrier to CDS adoption and effectiveness. The application of CDS best practices is resource intensive; thus, institutions often rely on commercially available CDS tools that are created to meet the generalized needs of many institutions and are not user centered. Beyond resource availability, insufficient guidance on how to address key aspects of implementation, such as contextual factors, may also limit the application of CDS best practices.

Patient Treatment Preferences for Heart Failure Medications: A Mixed Methods Study.

Introduction: Consideration of patient preferences for guideline-directed medical therapies (GDMT) for heart failure with reduced ejection fraction (HFrEF) may help improve major gaps in prescribing and adherence. This study aimed to identify the range and relative priority of factors influencing patients' decisions to take HFrEF medications.

Materials And Methods: This was a convergent mixed methods study of patients with HFrEF.

Integrating the Practical Robust Implementation and Sustainability Model With Best Practices in Clinical Decision Support Design: Implementation Science Approach.

Background: Clinical decision support (CDS) design best practices are intended to provide a narrative representation of factors that influence the success of CDS tools. However, they provide incomplete direction on evidence-based implementation principles.

Objective: This study aims to describe an integrated approach toward applying an existing implementation science (IS) framework with CDS design best practices to improve the effectiveness, sustainability, and reproducibility of CDS implementations.

Recent developments in diagnostics and treatment of neonatal cholestasis.

Neonatal cholestasis is characterized by conjugated hyperbilirubinemia in the newborn and young infant and is a sign common to over 100 hepatobiliary and/or metabolic disorders. A timely evaluation for its etiology is critical in order to quickly identify treatable causes such as biliary atresia, many of which benefit from early therapy. An expanding group of molecularly defined disorders involving bile formation, canalicular transporters, tight junction proteins and inborn errors of metabolism are being continuously discovered because of advances in genetic testing and bioinformatics.