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We have investigated the effect of dye distribution on the electrochemiluminescence (ECL) intensity measured with a simplified magnetic bead-based immunoassay for two families of silica nanoparticles (NPs) doped with the cationic Ru(bpy) 3 2+ and the zwitterionic Ru(bpy) 2 bps complexes (bps = bathophenanthroline disulfonate). The NPs doped with the Ru(bpy) 2 bps complex, which can efficiently self-organize in the NP volume favoring ECL generation, resulted in 150-400% signal enhancement compared to the Ru(bpy) 3 2+ -doped ones.

Thermally Activated Delayed Fluorescent (TADF) luminophores offer the potential to achieve 100% Internal Quantum Efficiency (IQE) by harvesting both singlet and triplet excitons via reverse intersystem crossing from T 1 to S 1 . This class of molecules has therefore been embraced in the pursuit of cheaper and more efficient electrochemiluminescent (ECL) labels. The present study explores how tuning the electron-donating (D) and -accepting (A) strengths of peripheral substituents affects the ECL emission of mono- and dicyanoarene-based TADF dyes. To this end, we synthesized two series of TADF compounds, independently manipulating electron donors and acceptors by (i) halogenating electron-rich diphenylamine moieties, or (ii) mono- or di-substituting the electron-poor cyanoarene core with either fluorine or imidazole. Through a comparative analysis, we elucidate the role of each substituent in shaping the photophysics of the investigated luminophores. Despite only achieving a relative Φ ECL as high as 1.27%, this framework identifies several molecular features that boost the ECL efficiency to pave the way for designing highly efficient TADF-based ECL emitters. Ultimately, imidazole substituents are exploited as a platform for functionalization with triethylene glycol units. The resulting water-soluble TADF luminophores are characterized under conditions usual to commercial ECL bioanalysis, proving their potential as a cost-effective alternative replacement to [Ru(bpy) 3 ] 2+ in clinical diagnostic., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The cytokine interferon-gamma (IFNγ) plays a multifaceted role in intestinal immune responses ranging from anti- to pro-inflammatory depending on the setting. Here, using a 3D co-culture system based on human intestinal epithelial organoids, we explore the capacity of IFNγ-exposure to reprogram intestinal epithelia and thereby directly modulate lymphocyte responses. IFNγ treatment of organoids led to transcriptional reprogramming, marked by a switch to a pro-inflammatory gene expression profile, including transcriptional upregulation of the chemokines CXCL9, CXCL10, and CXCL11. Proteomic analysis of organoid-conditioned medium post-treatment confirmed chemokine secretion. IFNγ-treatment of organoids led to enhanced T cell migration in a CXCL11-dependent manner without affecting T cell activation status. Taken together, our results suggest a specific role for CXCL11 in T cell recruitment that could be targeted to prevent T cell trafficking to the inflamed intestine., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Mental health and substance use disorders affect the lives of many people worldwide. Prevention and treatment of these conditions is important for optimal health and wellbeing, yet service access barriers are common. Virtual models of care may help to reduce barriers to receiving care. However, to facilitate uptake and use of virtual services, they need to appeal to patients and clinicians. This systematic review aimed to synthesise preference elicitation studies to determine what features of virtual mental health and substance use care are preferred by service users and service providers. Following the PRISMA guidelines for systematic reviews, we searched PubMed, PsycINFO, EconLit, MEDLINE, CINAHL, Academic Search Ultimate, and ProQuest Central for all available studies from database inception until May 2023. The Mixed Methods Appraisal Tool was used to assess the methodological quality of included studies. Nineteen studies met the eligibility criteria. However, none examined preferences for elements of different models of virtual care. Across the included studies, we identified 41 unique features that mapped to four themes of mental health and substance use care ('service', 'treatment', 'clinician' and 'additional supports'). Participant preferences were for individual, in-person, effective, flexible, and low-cost treatment. These preferences varied based on demographic factors, such as culture, gender, and participant type (e.g., patients, clinicians, general population). A user-centred approach should be adopted when designing and implementing mental health and substance use services. While preferences for features of mental health and substance use services more broadly are known, preferences for different models of virtual care remain unexplored. Future research should examine what features of virtual services would lead to optimal uptake and use across different users and stakeholders., (© 2024. The Author(s).)

A sulfonated tris(1-phenylpyrazolato)iridium(III) complex ([Ir(sppz) 3 ] 3- ) serves as a proof-of-concept non-emissive enhancer of the widely used ECL detection system of tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy) 3 ] 2+ ) with tri-n-propylamine (TPrA) co-reactant, acting through electrocatalysis of TPrA oxidation and efficient chemi-excitation of the luminophore. Using self-interference ECL spectroscopy, we show that the enhancer extends diffusion of the required electrogenerated precursors from the electrode surface. Previously reported enhancement through these pathways has been confounded by the inherent ECL of the enhancer, but the increase in [Ru(bpy) 3 ] 2+ ECL intensity using [Ir(sppz) 3 ] 3- was obtained without its concomitant emission. The most prominent enhancement (11-fold) occurred at low potentials associated with the 'indirect' co-reactant ECL pathway, which translated to between 2- and 6-fold enhancement when the luminophore was immobilised on microbeads as a general model for enhanced ECL assays., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objectives: This study investigated the relationship between numeracy skills (NS) and choice consistency in discrete choice experiments (DCEs)., Methods: A DCE was conducted to explore patients' preferences for kidney transplantation in Italy. Patients completed the DCE and answered 3-item numeracy questions. A heteroskedastic multinomial logit model was used to investigate the effect of numeracy on choice consistency., Results: Higher NS were associated with greater choice consistency, increasing the scale to 1.63 (P < .001), 1.39 (P < .001), and 1.18 (P < .001) for patients answering 3 of 3, 2 of 3, and 1 of 3 questions correctly, respectively, compared with those with no correct answers. This corresponded to 63%, 39%, and 18% more consistent choices, respectively. Accounting for choice consistency resulted in varying willingness-to-wait (WTW) estimates for kidney transplant attributes. Patients with the lowest numeracy (0/3) were willing to wait approximately 42 months [95% CI: 29.37, 54.68] for standard infectious risk, compared with 33 months [95% CI: 28.48, 38.09] for 1 of 3, 28 months [95% CI: 25.13, 30.32] for 2 of 3, and 24 months [95% CI: 20.51, 27.25] for 3 of 3 correct answers. However, WTW differences for an additional year of graft survival and neoplastic risk were not statistically significant across numeracy levels. Supplementary analyses of 2 additional DCEs on COVID-19 vaccinations and rheumatoid arthritis, conducted online, supported these findings: higher NS were associated with more consistent choices across different disease contexts and survey formats., Conclusions: The findings suggested that combining patients with varying NS could bias WTW estimates, highlighting the need to consider numeracy in DCE data analysis and interpretation., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

The COVID-19 pandemic is one of the most significant public health crises in modern history, with considerable impacts on the policy frameworks of national governments. In response to the pandemic, non-pharmaceutical interventions (NPIs) and mass vaccination campaigns have been employed to protect vulnerable groups. Through the lens of Political Budget Cycle (PBC) theory, this study explores the interplay between incumbent electoral concerns and political dynamics in influencing the implementation of NPIs and vaccination rollout within the administrative regions of Italy and Spain during the period spanning June 2020 to July 2021. The results reveal that incumbents up for the next scheduled election are 5.8 % more likely to increase the stringency of containment measures than those that face a term limit. The findings also demonstrate that the seats of the incumbent and coalition parties in parliament and the number of parties in the coalition have a negative effect on both the efficiency of the vaccination rollout and the stringency of NPIs. Additionally, the competitiveness of the election emerges as an important predictor of the strictness of NPIs. Therefore, our results suggest that incumbents may strategically manipulate COVID-19 policy measures to optimize electoral outcomes. The study underscores the substantive influence of political incentives, competitive electoral environments, and government coalitions on policy formulation during health emergencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We developed a sensing strategy that mimics the bead-based electrogenerated chemiluminescence immunoassay. However, instead of the most common metal complexes, such as Ru or Ir, the luminophore is luminol. The electrogenerated chemiluminescence of luminol was promoted by in situ electrochemical generation of hydrogen peroxide at a boron-doped diamond electrode. The electrochemical production of hydrogen peroxide was achieved in a carbonate solution by an oxidation reaction, while at the same time, microbeads labelled with luminol were deposited on the electrode surface. For the first time, we proved that was possible to obtain light emission from luminol without its direct oxidation at the electrode. This new emission mechanism is obtained at higher potentials than the usual luminol electrogenerated chemiluminescence at 0.3-0.5 V, in conjunction with hydrogen peroxide production on boron-doped diamond at around 2-2.5 V (vs Ag/AgCl)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

In health insurance markets with regulated competition, regulators face the challenge of preventing risk selection. This paper provides a framework for analyzing the scope (i.e., potential actions by insurers and consumers) and incentives for risk selection in such markets. Our approach consists of three steps. First, we describe four types of risk selection: (a) selection by consumers in and out of the market, (b) selection by consumers between high- and low-value plans, (c) selection by insurers via plan design, and (d) selection by insurers via other channels such as marketing, customer service, and supplementary insurance. In a second step, we develop a conceptual framework of how regulation and features of health insurance markets affect the scope and incentives for risk selection along these four dimensions. In a third step, we use this framework to compare nine health insurance markets with regulated competition in Australia, Europe, Israel, and the United States., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Electrogenerated chemiluminescence (ECL) stands out as a remarkable phenomenon of light emission at electrodes initiated by electrogenerated species in solution. Characterized by its exceptional sensitivity and minimal background optical signals, ECL finds applications across diverse domains, including biosensing, imaging, and various analytical applications. This review aims to serve as a comprehensive guide to the utilization of ECL in analytical applications. Beginning with a brief exposition on the theory at the basis of ECL generation, we elucidate the diverse systems employed to initiate ECL. Furthermore, we delineate the principal systems utilized for ECL generation in analytical contexts, elucidating both advantages and challenges inherent to their use. Additionally, we provide an overview of different electrode materials and novel ECL-based protocols tailored for analytical purposes, with a specific emphasis on biosensing applications., (© 2024. The Author(s).)

Objective: Depression is highly prevalent and associated with increased hospitalisations and mortality among patients with heart failure (HF). This study will evaluate the effectiveness and cost-effectiveness of an online wellbeing program for patients discharged from hospital with acute decompensated heart failure (ADHF) in (i) improving emotional and physical wellbeing, and (ii) decreasing healthcare utilisation., Methods: Two-arm randomised controlled trial. Eligible patients with ADHF will be recruited pre-discharge from two hospitals. Five hundred and seventy participants will be randomised to receive the intervention (online enhanced care program for HF: 'Enhanced HF Care') or usual care. Enhanced HF Care includes health education (11 micro-learning modules) and monitoring of depression and clinical outcomes via fortnightly/monthly surveys for 6 months, with participants offered tailored advice via video email and SMS. Cardiac nurses track real-time patient data from a dashboard and receive automated email alerts when patients report medium- or high-risk levels of depression or clinical symptoms, to action where needed. General practitioners also receive automated alerts if patients report medium- or high-risk survey responses and are encouraged to schedule a patient consultation., Results: Sixty-five participants enrolled to-date. Co-primary outcomes ('Minnesota Living with Heart Failure Questionnaire' Emotional and Physical subscales) and healthcare utilisation (secondary outcome) at 1- and 6-month post-recruitment will be compared between treatment arms using linear mixed effects regression models., Conclusions: This study has the potential to reduce the burden of depression for patients with HF by prioritising urgent mental health needs and clinical symptoms while simultaneously empowering patients with self-care knowledge., Trial Registration: The trial was prospectively registered via the Australian New Zealand Clinical Trials Registry: ACTRN12622001289707. Issue date: 4 October 2022., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Global economic and health shocks, such as the 2008 global financial crisis and the COVID-19 pandemic typically impact healthcare financing and delivery. Cutler found that profound societal changes in the 20th century induced three waves of healthcare reform across seven major OECD countries. Our study investigates whether major crises in the 21st century induced similar reform waves. Through thematic analysis, we systematically compared health system changes in response to these shocks, using data from the Observatory on Health Systems and Policies and the OECD. Our analysis reveals similar overarching reform trends across countries in response to the 2008 economic crisis: a tendency toward re-centralization of health system governance to control and leverage the efficient rationalization of public health resources. This, to some extent, countered the effects of the market-based reforms of the previous wave. The reforms induced by the 2008 crisis were mediated by its repercussions on the countries' economies. In contrast, reforms in response to the pandemic aimed primarily to address the direct impact of the shock on the health system. Despite its negative economic impact, the pandemic resulted in a substantial but temporary increase in public health spending. A better understanding reform dynamics and their impact on overarching conflicting health system objectives may prevent unintended consequences and enhance health systems' resilience in response to future shocks., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Health systems' insurance/funding can be organised in several ways. Some countries have adopted systems with a mixture of public-private involvement (e.g. Australia, Chile, Ireland, South Africa, New Zealand) which creates two-tier health systems, allowing consumers (groups) to have preferential access to the basic standard of care (e.g. skipping waiting times). The degree to which efficiency and equity are achieved in these types of systems is questioned. In this paper, we consider integration of the two tiers by means of a managed competition model, which underpins Social Health Insurance (SHI) systems. We elaborate a two-part conceptual framework, where, first, we review and update the existing pre-requisites for the model of managed competition to fit a broader definition of health systems, and second, we typologise possible roadmaps to achieve that model in terms of the insurance function, and focus on the consequences on providers and governance/stewardship.

Background: Despite the potential for improved population mental health and wellbeing, the integration of mental health digital interventions has been difficult to achieve. In this qualitative systematic review, we aimed to identify barriers and facilitators to the implementation of digital technologies in mental healthcare systems, and map these to an implementation framework to inform policy development., Methods: We searched Medline, Embase, Scopus, PsycInfo, Web of Science, and Google Scholar for primary research articles published between January 2010 and 2022. Studies were considered eligible if they reported barriers and/or facilitators to the integration of any digital mental healthcare technologies. Data were extracted using EPPI-Reviewer Web and analysed thematically via inductive and deductive cycles., Results: Of 12,525 references identified initially, 81 studies were included in the final analysis. Barriers and facilitators were grouped within an implementation (evidence-practice gap) framework across six domains, organised by four levels of mental healthcare systems. Broadly, implementation was hindered by the perception of digital technologies as impersonal tools that add additional burden of care onto both providers and patients, and change relational power asymmetries; an absence of resources; and regulatory complexities that impede access to universal coverage. Facilitators included person-cantered approaches that consider patients' intersectional features e.g., gender, class, disability, illness severity; evidence-based training for providers; collaboration among colleagues; appropriate investment in human and financial resources; and policy reforms that tackle universal access to digital health., Conclusion: It is important to consider the complex and interrelated nature of barriers across different domains and levels of the mental health system. To facilitate the equitable, sustainable, and long-term digital transition of mental health systems, policymakers should consider a systemic approach to collaboration between public and private sectors to inform evidence-based planning and strengthen mental health systems., Protocol Registration: The protocol is registered on PROSPERO, CRD42021276838., (© 2024. The Author(s).)

The Australian health system is characterised by high quality care by international standards, produced by a mix of public and private provision and funding of healthcare services. Despite good overall results, three issues are of concern. The first issue relates to the public procurement of healthcare, whose flaws have impacted individuals' access to care, and the high out-of-pocket spending. The second issue concerns the sustainability of the private health insurance market, given the government's goal of relieving cost and capacity from the public scheme, incentivising participation. Third, there are existing inefficiencies and inequities related to the duplication resulting from the interaction between public and private schemes. To ensure a sustainable, efficient and equitable health system, structural reforms are necessary to achieve long-term performance improvements. Using a framework for mixed public-private health systems, we assess the extent to which the Australian healthcare system achieves preconditions for efficiency and affordability in competitive healthcare markets.