Cost-effectiveness analysis of endoscopic eradication therapy for treatment of high-grade dysplasia in Barrett's esophagus

AIM: The aim was to evaluate the cost-effectiveness of endoscopic eradication therapy (EET) with combined endoscopic mucosal resection and radiofrequency ablation for the treatment of high-grade dysplasia (HGD) arising in patients with Barrett's esophagus compared with endoscopic surveillance alone in the UK. MATERIALS & METHODS: The cost-effectiveness model consisted of a decision tree and modified Markov model. A lifetime time horizon was adopted with the perspective of the UK healthcare system. RESULTS: The base case analysis estimates that EET for the treatment of HGD is cost-effective at a GB£20,000 cost-effectiveness threshold compared with providing surveillance alone for HGD patients (incremental cost-effectiveness ratio: GB£1272). CONCLUSION: EET is likely to be a cost-effective treatment strategy compared with surveillance alone in patients with HGD arising in Barrett's esophagus in the UK

Smoking Cessation: A Comparison of Two Model Structures

BACKGROUND: Most economic evaluations of smoking cessation interventions have used cohort state-transition models. Discrete event simulations (DESs) have been proposed as a superior approach. OBJECTIVE: We developed a state-transition model and a DES using the discretely integrated condition event (DICE) framework and compared the cost-effectiveness results. We performed scenario analysis using the DES to explore the impact of alternative assumptions. METHODS: The models estimated the costs and quality-adjusted life years (QALYs) for the intervention and comparator from the perspective of the UK National Health Service and Personal Social Services over a lifetime horizon. The models considered five comorbidities: chronic obstructive pulmonary disease, myocardial infarction, coronary heart disease, stroke and lung cancer. The state-transition model used prevalence data, and the DES used incidence. The costs and utility inputs were the same between two models and consistent with those used in previous analyses for the National Institute for Health and Care Excellence. RESULTS: In the state-transition model, the intervention produced an additional 0.16 QALYs at a cost of £540, leading to an incremental cost-effectiveness ratio (ICER) of £3438. The comparable DES scenario produced an ICER of £5577. The ICER for the DES increased to £18,354 when long-term relapse was included. CONCLUSIONS: The model structures themselves did not influence smoking cessation cost-effectiveness results, but long-term assumptions did. When there is variation in long-term predictions between interventions, economic models need a structure that can reflect this

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19

\ua9 2023 The Author(s)Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Methods: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Findings: Forty patients (32M:8F, age: 22–98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. Interpretation: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. Funding: UK Research and Innovation/ Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust

Label-free cell cycle analysis for high-throughput imaging flow cytometry

Imaging flow cytometry combines the high-throughput capabilities of conventional flow cytometry with single-cell imaging. Here we demonstrate label-free prediction of DNA content and quantification of the mitotic cell cycle phases by applying supervised machine learning to morphological features extracted from brightfield and the typically ignored darkfield images of cells from an imaging flow cytometer. This method facilitates non-destructive monitoring of cells avoiding potentially confounding effects of fluorescent stains while maximizing available fluorescence channels. The method is effective in cell cycle analysis for mammalian cells, both fixed and live, and accurately assesses the impact of a cell cycle mitotic phase blocking agent. As the same method is effective in predicting the DNA content of fission yeast, it is likely to have a broad application to other cell types

Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease

A New Evolutionary Algorithm-Based Home Monitoring Device for Parkinson’s Dyskinesia

Parkinson’s disease (PD) is a neurodegenerative movement disorder. Although there is no cure, symptomatic treatments are available and can significantly improve quality of life. The motor, or movement, features of PD are caused by reduced production of the neurotransmitter dopamine. Dopamine deficiency is most often treated using dopamine replacement therapy. However, this therapy can itself lead to further motor abnormalities referred to as dyskinesia. Dyskinesia consists of involuntary jerking movements and muscle spasms, which can often be violent. To minimise dyskinesia, it is necessary to accurately titrate the amount of medication given and monitor a patient’s movements. In this paper, we describe a new home monitoring device that allows dyskinesia to be measured as a patient goes about their daily activities, providing information that can assist clinicians when making changes to medication regimens. The device uses a predictive model of dyskinesia that was trained by an evolutionary algorithm, and achieves AUC>0.9 when discriminating clinically significant dyskinesia

Principles and processes behind promoting awareness of rights for quality maternal care services: a synthesis of stakeholder experiences and implementation factors

BACKGROUND: Promoting awareness of rights is a value-based process that entails a different way of thinking and acting, which is at times misunderstood or deemed as aspirational. METHODS: Guided by the SURE framework, we undertook a secondary analysis of 26 documents identified by an earlier systematic review on promoting awareness of rights to increase use of maternity care services. We thematically analysed stakeholder experiences and implementation factors across the diverse initiatives to derive common elements to guide future efforts. RESULTS: Interventions that promote awareness of rights for maternal health varied in nature, methodological orientation, depth and quality. Materials included booklets, posters, pamphlets/ briefs and service standards/charters. Target populations included women, family members, communities, community structures, community-based and non governmental organizations, health providers and administrators, as well as elected representatives. While one initiative only focused on raising awareness, most were embedded within larger efforts to improve the accountability and responsiveness of service delivery through community monitoring and advocacy, with a few aiming to change policies and contest elections. Underlying these action oriented forms of promoting awareness of rights, was a critical consciousness and attitudinal change gained through iterative capacity-building for all stakeholders; materials and processes that supported group discussion and interaction; the formation or strengthening of community groups; situational analysis to ensure adaptation to local context; facilitation to ensure common ground and language across stakeholders; and strategic networking and alliance building across health system levels. While many positive experiences are discussed, few challenges or barriers to implementation are documented. The limited documentation and poor quality of information found indicate that while various examples of promoting awareness of rights for maternal health exists, research partnerships to systematically evaluate their processes, learning and effects are lacking. CONCLUSION: Rather than being aspirational, several examples of promoting awareness of women’s rights for quality maternity care services exist. More than mainly disseminate information, they aim to change stakeholder mindsets and relationships across health system levels. Due to their transformatory intent they require sustained investment, with strategic planning, concrete operationalization and political adeptness to manage dynamic stakeholder expectations and reactions overtime. More investment is also required in research partnerships that support such initiatives and better elucidate their context specific variations.ScopusIS

A Systematic Review of the Effect of Cognitive Strategies on Strength Performance

Background Researchers have tested the beliefs of sportspeople and sports medicine specialists that cognitive strategies influence strength performance. Few investigators have synthesised the literature. Objectives The specific objectives were to review evidence regarding (a) the cognitive strategy–strength performance relationship; (b) participant skill level as a moderator; and (c) cognitive, motivational, biomechanical/physiological, and emotional mediators. Method Studies were sourced via electronic databases, reference lists of retrieved articles, and manual searches of relevant journals. Studies had to be randomised or counterbalanced experiments with a control group or condition, repeated measures, and a quality control score above 0.5 (out of 1). Cognitive strategies included goal setting, imagery, self-talk, preparatory arousal, and free choice. Dependent variables included maximal strength, local muscular endurance, or muscular power. Results Globally, cognitive strategies were reliability associated with increased strength performance (results ranged from 61 to 65 %). Results were mixed when examining the effects of specific strategies on particular dependent variables, although no intervention had an overall negative influence. Indeterminate relationships emerged regarding hypothesised mediators (except cognitive variables) and participant skill level as a moderator. Conclusions Although cognitive strategies influence strength performance, there are knowledge gaps regarding specific types of strength, especially muscular power. Cognitive variables, such as concentration, show promise as possible mediators