Rationale and Design of Healthy at Home for COPD: an Integrated Remote Patient Monitoring and Virtual Pulmonary Rehabilitation Pilot Study.

Chronic Obstructive Pulmonary Disease (COPD) is a common, costly, and morbid condition. Pulmonary rehabilitation, close monitoring, and early intervention during acute exacerbations of symptoms represent a comprehensive approach to improve outcomes, but the optimal means of delivering these services is uncertain. Logistical, financial, and social barriers to providing healthcare through face-to-face encounters, paired with recent developments in technology, have stimulated interest in exploring alternative models of care. The Healthy at Home study seeks to determine the feasibility of a multimodal, digitally enhanced intervention provided to participants with COPD longitudinally over six months. This paper details the recruitment, methods, and analysis plan for the study, which is recruiting 100 participants in its pilot phase. Participants were provided with several integrated services including a smartwatch to track physiological data, a study app to track symptoms and study instruments, access to a mobile integrated health program for acute clinical needs, and a virtual comprehensive pulmonary support service. Participants shared physiologic, demographic, and symptom reports, electronic health records, and claims data with the study team, facilitating a better understanding of their symptoms and potential care needs longitudinally. The Healthy at Home study seeks to develop a comprehensive digital phenotype of COPD by tracking and responding to multiple indices of disease behavior and facilitating early and nuanced responses to changes in participants' health status. This study is registered at Clinicaltrials.gov (NCT06000696).

Tools to Promote Shared Decision-Making in Lung Cancer Screening Using Low-Dose CT Scanning: A Systematic Review.

BACKGROUND: Decisions about lung cancer screening are inherently complex and create a need for methods to convey the risks and benefits of screening to patients. RESEARCH QUESTION: What kind of decision aids or tools are available to support shared decision-making for lung cancer screening? What is the current evidence for the effectiveness, acceptability, and feasibility of those tools? STUDY DESIGN AND METHODS: We conducted a systematic review of studies and searched PubMed, MEDLINE, EMBASE, Cochrane Clinical Trials Register, and ClinicalTrials.gov from inception to December 2019 for studies that evaluated the effectiveness and acceptability of tools to promote shared decision-making for patients who are considering lung cancer screening. RESULTS: After screening 2,427 records, we included one randomized control trial, two observational studies, 11 before/after studies of a decision aid or an educational tool. Fifteen distinct tools in various formats were evaluated in 14 studies. Most studies were of fair quality. Studies reported improvement in patients' knowledge of lung cancer screening (n = 9 studies), but improvements in specific areas of knowledge were inconsistent. Decisional conflict was low or reduced after the administration of the tools (n = 7 studies). The acceptability of tools was rated as "high" by patients (n = 7 studies) and physicians (n = 1 study). Low dose CT scan completion rates varied among studies (n = 6 studies). INTERPRETATION: Evidence from 14 studies suggests that some elements of existing tools for lung cancer screening may help to prepare patients for decision-making by improving knowledge and reducing decisional conflict. Such tools generally are acceptable to patients and providers. Further studies that use consistent measures and reporting methods and assess relevant decisional and clinical outcomes are needed to determine the comparative effectiveness and feasibility of implementation of these tools. CLINICAL TRIAL REGISTRATION: PROSPERO 2018 CRD4201874814.

Stoichiometry and Change of the mRNA Closed-Loop Factors as Translating Ribosomes Transit from Initiation to Elongation.

Protein synthesis is a highly efficient process and is under exacting control. Yet, the actual abundance of translation factors present in translating complexes and how these abundances change during the transit of a ribosome across an mRNA remains unknown. Using analytical ultracentrifugation with fluorescent detection we have determined the stoichiometry of the closed-loop translation factors for translating ribosomes. A variety of pools of translating polysomes and monosomes were identified, each containing different abundances of the closed-loop factors eIF4E, eIF4G, and PAB1 and that of the translational repressor, SBP1. We establish that closed-loop factors eIF4E/eIF4G dissociated both as ribosomes transited polyadenylated mRNA from initiation to elongation and as translation changed from the polysomal to monosomal state prior to cessation of translation. eIF4G was found to particularly dissociate from polyadenylated mRNA as polysomes moved to the monosomal state, suggesting an active role for translational repressors in this process. Consistent with this suggestion, translating complexes generally did not simultaneously contain eIF4E/eIF4G and SBP1, implying mutual exclusivity in such complexes. For substantially deadenylated mRNA, however, a second type of closed-loop structure was identified that contained just eIF4E and eIF4G. More than one eIF4G molecule per polysome appeared to be present in these complexes, supporting the importance of eIF4G interactions with the mRNA independent of PAB1. These latter closed-loop structures, which were particularly stable in polysomes, may be playing specific roles in both normal and disease states for specific mRNA that are deadenylated and/or lacking PAB1. These analyses establish a dynamic snapshot of molecular abundance changes during ribosomal transit across an mRNA in what are likely to be critical targets of regulation.

Use of the novel technique of analytical ultracentrifugation with fluorescence detection system identifies a 77S monosomal translation complex.

A fundamental problem in proteomics is the identification of protein complexes and their components. We have used analytical ultracentrifugation with a fluorescence detection system (AU-FDS) to precisely and rapidly identify translation complexes in the yeast Saccharomyces cerevisiae. Following a one-step affinity purification of either poly(A)-binding protein (PAB1) or the large ribosomal subunit protein RPL25A in conjunction with GFP-tagged yeast proteins/RNAs, we have detected a 77S translation complex that contains the 80S ribosome, mRNA, and components of the closed-loop structure, eIF4E, eIF4G, and PAB1. This 77S structure, not readily observed previously, is consistent with the monosomal translation complex. The 77S complex abundance decreased with translational defects and following the stress of glucose deprivation that causes translational stoppage. By quantitating the abundance of the 77S complex in response to different stress conditions that block translation initiation, we observed that the stress of glucose deprivation affected translation initiation primarily by operating through a pathway involving the mRNA cap binding protein eIF4E whereas amino acid deprivation, as previously known, acted through the 43S complex. High salt conditions (1M KCl) and robust heat shock acted at other steps. The presumed sites of translational blockage caused by these stresses coincided with the types of stress granules, if any, which are subsequently formed.