Redesigning Systems to Improve Teamwork and Quality for Hospitalized Patients (RESET): Study Protocol Evaluating the Effect of Mentored Implementation to Redesign Clinical Microsystems

Background: A number of challenges impede our ability to consistently provide high quality care to patients hospitalized with medical conditions. Teams are large, team membership continually evolves, and physicians are often spread across multiple units and floors. Moreover, patients and family members are generally poorly informed and lack opportunities to partner in decision making. Prior studies have tested interventions to redesign aspects of the care delivery system for hospitalized medical patients, but the majority have evaluated the effect of a single intervention. We believe these interventions represent complementary and mutually reinforcing components of a redesigned clinical microsystem. Our specific objective for this study is to implement a set of evidence-based complementary interventions across a range of clinical microsystems, identify factors and strategies associated with successful implementation, and evaluate the impact on quality. Methods: The RESET project uses the Advanced and Integrated MicroSystems (AIMS) interventions. The AIMS interventions consist of 1) Unit-based Physician Teams, 2) Unit Nurse-Physician Co-leadership, 3) Enhanced Interprofessional Rounds, 4) Unit-level Performance Reports, and 5) Patient Engagement Activities. Four hospital sites were chosen to receive guidance and resources as they implement the AIMS interventions. Each study site has assembled a local leadership team, consisting of a physician and nurse, and receives mentorship from a physician and nurse with experience in leading similar interventions. Primary outcomes include teamwork climate, assessed using the Safety Attitudes Questionnaire, and adverse events using the Medicare Patient Safety Monitoring System (MPSMS). RESET uses a parallel group study design and two group pretest-posttest analyses for primary outcomes. We use a multi-method approach to collect and triangulate qualitative data collected during 3 visits to study sites. We will use cross-case comparisons to consider how site-specific contextual factors interact with the variation in the intensity and fidelity of implementation to affect teamwork and patient outcomes. Discussion: The RESET study provides mentorship and resources to assist hospitals as they implement complementary and mutually reinforcing components to redesign the clinical microsystems caring for medical patients. Our findings will be of interest and directly applicable to all hospitals providing care to patients with medical conditions. Trial Registration: NCT03745677. Retrospectively registered on November 19, 2018

Meridional overturning circulation in the South Atlantic at the last glacial maximum

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 7 (2006): Q10N03, doi:10.1029/2005GC001226.The geostrophic shear associated with the meridional overturning circulation is reflected in the difference in density between the eastern and western margins of the ocean basin. Here we examine how the density difference across 30°S in the upper 2 km of the Atlantic Ocean (and thus the magnitude of the shear associated with the overturning circulation) has changed between the last glacial maximum and the present. We use oxygen isotope measurements on benthic foraminifera to reconstruct density. Today, the density in upper and intermediate waters along the eastern margin in the South Atlantic is greater than along the western margin, reflecting the vertical shear associated with the northward flow of surface and intermediate waters and the southward flowing North Atlantic Deep Waters below. The greater density along the eastern margin is reflected in the higher δ 18O values for surface sediment benthic foraminifera than those found on the western margin for the upper 2 km. For the last glacial maximum the available data indicate that the eastern margin foraminifera had similar δ 18O to those on the western margin between 1 and 2 km and that the gradient was reversed relative to today with the higher δ 18O values in the western margin benthic foraminifera above 1 km. If this reversal in benthic foraminifera δ 18O gradient reflects a reversal in seawater density gradient, these data are not consistent with a vigorous but shallower overturning cell in which surface waters entering the Atlantic basin are balanced by the southward export of Glacial North Atlantic Intermediate Water.This work was supported by NSF award OCE-9984989/OCE-0428803 to J.L.-S., NSF award OCE-9986748 to D.W.O. and W.B.C., NSF OCE-0222111 to C.D.C., and SEGRF fellowship at LLNL to J.M

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial

Background: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. Methods: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation.Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. Discussion: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. Trial registration: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture.

The prostate epithelium is comprised predominantly of basal and luminal cells. In vivo lineage tracing has been utilized to define the differentiation capacity of mouse prostate basal and luminal cells during development, tissue-regeneration and transformation. However, evaluating cell-intrinsic and extrinsic regulators of prostate epithelial differentiation capacity using a lineage tracing approach often requires extensive breeding and can be cost-prohibitive. In the prostate organoid assay, basal and luminal cells generate prostatic epithelium ex vivo. Importantly, primary epithelial cells can be isolated from mice of any genetic background or mice treated with any number of small molecules prior to, or after, plating into three-dimensional (3D) culture. Sufficient material for evaluation of differentiation capacity is generated after 7-10 days. Collection of basal-derived and luminal-derived organoids for (1) protein analysis by Western blot and (2) immunohistochemical analysis of intact organoids by whole-mount confocal microscopy enables researchers to evaluate the ex vivo differentiation capacity of prostate epithelial cells. When used in combination, these two approaches provide complementary information about the differentiation capacity of prostate basal and luminal cells in response to genetic or pharmacological manipulation

Aging of the progenitor cells that initiate prostate cancer.

Many organs experience a loss of tissue mass and a decline in regenerative capacity during aging. In contrast, the prostate continues to grow in volume. In fact, age is the most important risk factor for prostate cancer. However, the age-related factors that influence the composition, morphology and molecular features of prostate epithelial progenitor cells, the cells-of-origin for prostate cancer, are poorly understood. Here, we review the evidence that prostate luminal progenitor cells are expanded with age. We explore the age-related changes to the microenvironment that may influence prostate epithelial cells and risk of transformation. Finally, we raise a series of questions about models of aging and regulators of prostate aging which need to be addressed. A fundamental understanding of aging in the prostate will yield critical insights into mechanisms that promote the development of age-related prostatic disease

Redesigning systems to improve teamwork and quality for hospitalized patients (RESET): study protocol evaluating the effect of mentored implementation to redesign clinical microsystems

Abstract Background A number of challenges impede our ability to consistently provide high quality care to patients hospitalized with medical conditions. Teams are large, team membership continually evolves, and physicians are often spread across multiple units and floors. Moreover, patients and family members are generally poorly informed and lack opportunities to partner in decision making. Prior studies have tested interventions to redesign aspects of the care delivery system for hospitalized medical patients, but the majority have evaluated the effect of a single intervention. We believe these interventions represent complementary and mutually reinforcing components of a redesigned clinical microsystem. Our specific objective for this study is to implement a set of evidence-based complementary interventions across a range of clinical microsystems, identify factors and strategies associated with successful implementation, and evaluate the impact on quality. Methods The RESET project uses the Advanced and Integrated MicroSystems (AIMS) interventions. The AIMS interventions consist of 1) Unit-based Physician Teams, 2) Unit Nurse-Physician Co-leadership, 3) Enhanced Interprofessional Rounds, 4) Unit-level Performance Reports, and 5) Patient Engagement Activities. Four hospital sites were chosen to receive guidance and resources as they implement the AIMS interventions. Each study site has assembled a local leadership team, consisting of a physician and nurse, and receives mentorship from a physician and nurse with experience in leading similar interventions. Primary outcomes include teamwork climate, assessed using the Safety Attitudes Questionnaire, and adverse events using the Medicare Patient Safety Monitoring System (MPSMS). RESET uses a parallel group study design and two group pretest-posttest analyses for primary outcomes. We use a multi-method approach to collect and triangulate qualitative data collected during 3 visits to study sites. We will use cross-case comparisons to consider how site-specific contextual factors interact with the variation in the intensity and fidelity of implementation to affect teamwork and patient outcomes. Discussion The RESET study provides mentorship and resources to assist hospitals as they implement complementary and mutually reinforcing components to redesign the clinical microsystems caring for medical patients. Our findings will be of interest and directly applicable to all hospitals providing care to patients with medical conditions. Trial registration NCT03745677. Retrospectively registered on November 19, 2018