Reconstructed signaling and regulatory networks identify potential drugs for SARS-CoV-2 infection.

Several molecular datasets have been recently compiled to characterize the activity of SARS-CoV-2 within human cells. Here we extend computational methods to integrate several different types of sequence, functional and interaction data to reconstruct networks and pathways activated by the virus in host cells. We identify key proteins in these networks and further intersect them with genes differentially expressed at conditions that are known to impact viral activity.

Reassessment of Home Oxygen Prescription after Hospitalization for Chronic Obstructive Pulmonary Disease. A Potential Target for Deimplementation.

Hypoxemia associated with acute exacerbations of chronic obstructive pulmonary disease (COPD) often resolves with time. Current guidelines recommend that patients recently discharged with supplemental home oxygen after hospitalization should not have renewal of the prescription without assessment for hypoxemia. Understanding patterns of home oxygen reassessment is an opportunity to improve quality and value in home oxygen prescribing and may provide future targets for deimplementation.

Epithelial Stem and Progenitor Cells in Lung Repair and Regeneration.

The mammalian lung epithelium is composed of a wide array of specialized cells that have adapted to survive environmental exposure and perform the tasks necessary for respiration. Although the majority of these cells are remarkably quiescent during adult lung homeostasis, a growing body of literature has demonstrated the capacity of these epithelial lineages to proliferate in response to injury and regenerate lost or damaged cells. In this review, we focus on the regionally distinct lung epithelial cell types that contribute to repair after injury, and we address current controversies regarding whether elite stem cells or frequent facultative progenitors are the predominant participants.

Interventions to increase appointment attendance in safety net health centers: A systematic review and meta-analysis.

Rationale, Aims And Objectives: Missed appointments are a persistent problem across healthcare settings, and result in negative outcomes for providers and patients. We aimed to review and evaluate the effectiveness of interventions designed to reduce missed appointments in safety net settings.

Methods: We conducted a systematic review of interventions reported in three electronic databases.

Patient navigation among recently hospitalized smokers to promote tobacco treatment: Results from a randomized exploratory pilot study.

Introduction: Adding screening for health-related social needs to tobacco treatment interventions initiated during hospitalizations may improve intervention effectiveness among vulnerable populations. Our objective was to examine the effect the acceptability and feasibility of a intervention in which a patient navigator screens for and addresses social needs to increase receipt of smoking cessation medication among recently hospitalized smokers at a safety-net hospital.

Methods: In a two-group randomized exploratory pilot study, we assigned hospitalized smokers to either the Enhanced Traditional Control (ETC) group (list of smoking cessation resources) or ETC + Patient Navigation (up to 10 h of navigation over a 3-month period, in which a navigator screens for and addresses health-related social needs).

SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response.

A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here, we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture.

Provider anticipation and experience of patient reaction when deprescribing guideline discordant inhaled corticosteroids.

Introduction: Despite evidence of possible patient harm and substantial costs, medication overuse is persistent. Patient reaction is one potential barrier to deprescribing, but little research has assessed this in specific instances of medication discontinuation. We sought to understand Veteran and provider experience when de-implementing guideline-discordant use of inhaled corticosteroids (ICS) in those with mild-to-moderate chronic obstructive pulmonary disease (COPD).

Guiding Principles for the Conduct of Observational Critical Care Research for Coronavirus Disease 2019 Pandemics and Beyond: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study Registry.

Objectives: Use of observational data to inform the response and care of patients during a pandemic faces unique challenges.

Design: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID 2019 Registry Core data and research methodology team convened over virtual meetings throughout March to June 2020 to determine best practice goals for development of a pandemic disease registry to support rapid data collection and analysis.

Setting: International, multi-center registry of hospitalized patients.

Barriers and facilitators to implementing priority inpatient initiatives in the safety net setting.

Background: Safety net hospitals, which serve vulnerable and underserved populations and often operate on smaller budgets than non-safety net hospitals, may experience unique implementation challenges. We sought to describe common barriers and facilitators that affect the implementation of improvement initiatives in a safety net hospital, and identify potentially transferable lessons to enhance implementation efforts in similar settings.

Methods: We interviewed leaders within five inpatient departments and asked them to identify the priority inpatient improvement initiative from the last year.

Impact of Workplace Climate on Burnout Among Critical Care Nurses in the Veterans Health Administration.

Background: Burnout is a maladaptive response to work-related stress that is associated with negative consequences for patients, clinicians, and the health care system. Critical care nurses are at especially high risk for burnout. Previous studies of burnout have used survey methods that simultaneously measure risk factors and outcomes of burnout, potentially introducing common method bias.

Expression of Amyloidogenic Transthyretin Drives Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease.

The systemic amyloidoses are diverse disorders in which misfolded proteins are secreted by effector organs and deposited as proteotoxic aggregates at downstream tissues. Although well described clinically, the contribution of synthesizing organs to amyloid disease pathogenesis is unknown. Here, we utilize hereditary transthyretin amyloidosis (ATTR amyloidosis) induced pluripotent stem cells (iPSCs) to define the contribution of hepatocyte-like cells (HLCs) to the proteotoxicity of secreted transthyretin (TTR).

Patient characteristics associated with adherence to pulmonary nodule guidelines.

Background: While pulmonary nodule guidelines provide follow-up recommendations based on nodule size and malignancy risk, these are inconsistently followed in clinical practice. In this study, we sought to identify patient characteristics associated with guideline-concordant nodule follow-up.

Methods: We conducted a retrospective cohort study of patients diagnosed with a pulmonary nodule between 2011 and 2014 at Boston Medical Center.

Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19.

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10-15 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation.

Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors.

Development of an anti-SARS-CoV-2 therapeutic is hindered by the lack of physiologically relevant model systems that can recapitulate host-viral interactions in human cell types, specifically the epithelium of the lung. Here, we compare induced pluripotent stem cell (iPSC)-derived alveolar and airway epithelial cells to primary lung epithelial cell controls, focusing on expression levels of genes relevant for COVID-19 disease modeling. iPSC-derived alveolar epithelial type II-like cells (iAT2s) and iPSC-derived airway epithelial lineages express key transcripts associated with lung identity in the majority of cells produced in culture.

Hidden neural states underlie canary song syntax.

Coordinated skills such as speech or dance involve sequences of actions that follow syntactic rules in which transitions between elements depend on the identities and order of past actions. Canary songs consist of repeated syllables called phrases, and the ordering of these phrases follows long-range rules in which the choice of what to sing depends on the song structure many seconds prior. The neural substrates that support these long-range correlations are unknown.

The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness.

Unlabelled: The coronavirus disease 2019 pandemic has disproportionally strained intensive care services worldwide. Large areas of uncertainly regarding epidemiology, physiology, practice patterns, and resource demands for patients with coronavirus disease 2019 require rapid collection and dissemination of data. We describe the conception and implementation of an intensive care database rapidly developed and designed to meet data analytic needs in response to the coronavirus disease 2019 pandemic-the multicenter, international Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study.

Assessing the Course of Organ Dysfunction Using Joint Longitudinal and Time-to-Event Modeling in the Vasopressin and Septic Shock Trial.

Unlabelled: Non-mortality septic shock outcomes (e.g., Sequential Organ Failure Assessment score) are important clinical endpoints in pivotal sepsis trials.

Patient vs Clinician Perspectives on Communication About Results of Lung Cancer Screening: A Qualitative Study.

Background: In the incidental pulmonary nodule and breast cancer screening settings, high-quality patient-centered communication can improve adherence to evaluation and mitigate patient distress. Although guidelines emphasize shared decision-making before lung cancer screening, little is known about patient-clinician communication after lung cancer screening.

Research Question: How do patients and clinicians perceive communication and results notification after lung cancer screening, and are there approaches that may mitigate or exacerbate distress?

Study Design And Methods: We conducted interviews and focus groups with 49 patients who underwent lung cancer screening in the prior year and 36 clinicians who communicate screening results (primary care providers, pulmonologists, nurses), recruited from lung cancer screening programs at 4 hospitals.