Electrogenerated chemiluminescence from luminol-labelled microbeads triggered by in situ generation of hydrogen peroxide.

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).

Political determinants of COVID-19 restrictions and vaccine rollouts: The case of regional elections in Italy and Spain.

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.

Investigating the effect of an online enhanced care program on the emotional and physical wellbeing of patients discharged from hospital with acute decompensated heart failure: Study protocol for a randomised controlled trial: Enhanced care program for heart failure.

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.

From theory to practice: understanding the challenges in the implementation of electrogenerated chemiluminescence for analytical applications.

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.

The roads to managed competition for mixed public-private health systems: a conceptual framework.

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.

The dynamics of international health system reforms: Evidence of a new wave in response to the 2008 economic crisis and the COVID-19 pandemic?

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.

Barriers and facilitators to the implementation of digital technologies in mental health systems: a qualitative systematic review to inform a policy framework.

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.

Preconditions for efficiency and affordability in mixed health systems: are they fulfilled in the Australian public-private mix?

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.

Scope and Incentives for Risk Selection in Health Insurance Markets With Regulated Competition: A Conceptual Framework and International Comparison.

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.

Redox-mediated electrochemiluminescence enhancement for bead-based immunoassay.

Electrochemiluminescence (ECL) is a highly sensitive mode of detection utilised in commercialised bead-based immunoassays. Recently, the introduction of a freely diffusing water-soluble Ir(iii) complex was demonstrated to enhance the ECL emission of [Ru(bpy)3]2+ labels anchored to microbeads, but a comprehensive investigation of the proposed 'redox-mediated' mechanism was not carried out. In this work, we select three different water-soluble Ir(iii) complexes by virtue of their photophysical and electrochemical properties in comparison with those of the [Ru(bpy)3]2+ luminophore and the TPrA co-reactant. A systematic investigation of the influence of each Ir(iii) complex on the emission of the Ru(ii) labels on single beads by ECL microscopy revealed that the heterogeneous ECL can be finely tuned and either enhanced up to 107% or lowered by 75%. The variation of the [Ru(bpy)3]2+ ECL emission was correlated to the properties of each Ir(iii)-based mediator, which enabled us to decipher the mechanism of interaction and define guidelines for the future design of novel Ir(iii) complexes to further enhance the ECL emission of bead-based immunoassays. Ultimately, we showcase the potential of this technology for practical sample analysis in commercial instruments by assessing the enhancement of the collective ECL intensity from a bead-based system.

Optics Determines the Electrochemiluminescence Signal of Bead-Based Immunoassays.

Electrochemiluminescence (ECL) is an optical readout technique that is successfully applied for the detection of biomarkers in body fluids using microbead-based immunoassays. This technology is of utmost importance for in vitro diagnostics and thus a very active research area but is mainly focused on the quest for new dyes and coreactants, whereas the investigation of the ECL optics is extremely scarce. Herein, we report the 3D imaging of the ECL signals recorded at single microbeads decorated with the ECL labels in the sandwich immunoassay format. We show that the optical effects due to the light propagation through the bead determine mainly the spatial distribution of the recorded ECL signals. Indeed, the optical simulations based on the discrete dipole approximation compute rigorously the electromagnetic scattering of the ECL emission by the microbead and allow for reconstructing the spatial map of ECL emission. Thus, it provides a global description of the ECL chemical reactivity and the associated optics. The outcomes of this 3D imaging approach complemented by the optical modeling provide insight into the ECL optics and the unique ECL chemical mechanism operating on bead-based immunoassays. Therefore, it opens new directions for mechanistic investigations, ultrasensitive ECL bioassays, and imaging.

Dynamic Mapping of Electrochemiluminescence Reactivity in Space: Application to Bead-Based Assays.

As an electrochemical technique offering an optical readout, electrochemiluminescence (ECL) evolved recently into a powerful microscopy technique with the visualization of a wide range of microscopic entities. However, the dynamic imaging of transient ECL events did not receive intensive attention due to the limited number of electrogenerated photons. Here, the reaction kinetics of the model ECL bioassay system was revealed by dynamic imaging of single [Ru(bpy)3]2+-functionalized beads in the presence of the efficient tripropylamine coreactant. The time profile behavior of ECL emission, the variations of the ECL layer thickness, and the position of maximum ECL intensity over time were investigated, which were not achieved by static imaging in previous studies. Moreover, the dynamics of the ECL emission were confronted with the simulation. The reported dynamic ECL imaging allows the investigation of the ECL kinetics and mechanisms operating in bioassays and cell microscopy.

Interventions for improving clinical outcomes and health-related quality-of-life for people living with skeletal dysplasias: an evidence gap map.

PURPOSE: Skeletal dysplasias are rare genetic disorders that are characterized by abnormal development of bone and cartilage. There are multiple medical and non-medical treatments for specific symptoms of skeletal dysplasias e.g. pain, as well as corrective surgical procedures to improve physical functioning. The aim of this paper was to develop an evidence-gap map of treatment options for skeletal dysplasias, and their impact on patient outcomes. METHODS: We conducted an evidence-gap map to identify the available evidence on the impact of treatment options on people with skeletal dysplasias on clinical outcomes (such as increase in height), and dimensions of health-related quality of life. A structured search strategy was applied to five databases. Two reviewers independently assessed articles for inclusion in two stages: titles and abstracts (stage 1), and full text of studies retained at stage 2. RESULTS: 58 studies fulfilled our inclusion criteria. The included studies covered 12 types of skeletal dysplasia that are non-lethal with severe limb deformities that could result in significant pain and numerous orthopaedic interventions. Most studies reported on the effect of surgical interventions (n = 40, 69%), followed by the effect of treatments on dimensions of health quality-of-life (n = 4, 6.8%) and psychosocial functioning (n = 8, 13.8%). CONCLUSION: Most studies reported on clinical outcomes from surgery for people living with Achondroplasia. Consequently, there are gaps in the literature on the full range of treatment options (including no active treatment), outcomes and the lived experience of people living with other skeletal dysplasias. More research is warranted to examine the impact of treatments on health-related quality-of-life of people living with skeletal dysplasias, including their relatives to enable them to make preference- and valued based decisions about treatment.

Electrogenerated chemiluminescence at boron-doped diamond electrodes.

Electrogenerated chemiluminescence (ECL) refers to the phenomenon of light emission from molecular species which is triggered by an electrochemical reaction. Therefore, like most electrochemical systems, the electrode material plays a pivotal role and much effort has been made in order to find the best material for ECL, in terms of light signal intensity and long-term stability, especially after the development of ECL for analytical applications. In this article, we will introduce and highlight the distinctive features of boron-doped diamond (BDD) as an electrode material for ECL which has complementary properties compared to the most common metals (e.g., Au or Pt) and carbon materials (e.g., glassy carbon, carbon nanotubes and graphene). Boron-doped diamond electrodes emerged as novel electrodes, gaining more and more interest from the electrochemical community for their peculiar characteristics such as a wide solvent window, low capacitance, resistance to fouling and mechanical robustness. Furthermore, compared to metal electrodes, BDD does not form an oxide layer in aqueous solutions, and the sp3 carbon hybridization gives BDD the ability to enable peculiar electrochemical reactions that are not possible on sp2 carbon materials. Electrogenerated chemiluminescence investigations with boron-doped diamond electrodes have been reported for common ECL systems (luminophores and co-reactants), and special ECL that is only possible on BDD which includes the in situ electrochemical generation of the co-reactant.

Study protocol for an economic evaluation and budget impact of implementation strategies to support routine provision of antenatal care for gestational weight gain: a stepped-wedge cluster trial.

BACKGROUND: Antenatal clinical practice guidelines recommend routine assessment of weight and provision of advice on recommended weight gain during pregnancy and referral to additional services when appropriate. However, there are barriers to clinicians adopting such best-practice guidelines. Effective, cost-effective, and affordable implementation strategies are needed to ensure the intended benefits of guidelines are realised. This paper describes the protocol for evaluating the efficiency and affordability of implementation strategies compared to the usual practice in public antenatal services. METHOD: The prospective trial-based economic evaluation will identify, measure, and value key resource and outcome impacts arising from the implementation strategies compared with usual practice. The evaluation will comprise of (i) costing, (ii) cost-consequence analyses, where a scorecard approach will be used to show the costs and benefits given the multiple primary outcomes included in the trial, and (iii) cost-effectiveness analysis, where the primary outcome will be incremental cost per percent increase in participants reporting receipt of antenatal care for gestational weight gain consistent with the guideline recommendations. Affordability will be evaluated using (iv) budget impact assessment and will estimate the financial implications of adoption and diffusion of this implementation strategy from the perspective of relevant fund-holders. DISCUSSION: Together with the findings from the effectiveness trial, the outcomes of this economic evaluation will inform future healthcare policy, investment allocation, and research regarding the implementation of antenatal care to support healthy gestational weight gain. TRIAL REGISTRATION: Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12621000054819 (22/01/2021) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380680&isReview=true .

Bimodal Electrochemiluminescence Microscopy of Single Cells.

Electrochemiluminescence (ECL) microscopy is an emerging technique with new applications such as imaging of single entities and cells. Herein, we have developed a bimodal and bicolor approach to record both positive ECL (PECL: light-emitting object on dark background) and shadow label-free ECL (SECL: nonemissive object shadowing the background luminescence) images of single cells. This bimodal approach is the result of the simultaneous emissions of [Ru(bpy)3]2+ used to label the cellular membrane (PECL) and [Ir(sppy)3]3- dissolved in solution (SECL). By spectrally resolving the ECL emission wavelengths, we recorded the images of the same cells in both PECL and SECL modes using the [Ru(bpy)3]2+ (λmax = 620 nm) and [Ir(sppy)3]3- (λmax = 515 nm) luminescence, respectively. PECL shows the distribution of the [Ru(bpy)3]2+ labels attached to the cellular membrane, whereas SECL reflects the local diffusional hindrance of the ECL reagents by each cell. The high sensitivity and surface-confined features of the reported approach are demonstrated by imaging cell-cell contacts during the mitosis process. Furthermore, the comparison of PECL and SECL images demonstrates the differential diffusion of tri-n-propylamine and [Ir(sppy)3]3- through the permeabilized cell membranes. Consequently, this dual approach enables the imaging of the morphology of the cell adhering on the surface and can significantly contribute to multimodal ECL imaging and bioassays with different luminescent systems.

Electrochemical Characterization and CO2 Reduction Reaction of a Family of Pyridazine-Bridged Dinuclear Mn(I) Carbonyl Complexes.

Three recently synthesized neutral dinuclear carbonyl manganese complexes with the pyridazine bridging ligand, of general formula [Mn2(µ-ER)2(CO)6(µ-pydz)] (pydz = pyridazine; E = O or S; R = methyl or phenyl), have been investigated by cyclic voltammetry in dimethylformamide and acetonitrile both under an inert argon atmosphere and in the presence of carbon dioxide. This family of Mn(I) compounds behaves interestingly at negative potentials in the presence of CO2. Based on this behavior, which is herein discussed, a rather efficient catalytic mechanism for the CO2 reduction reaction toward the generation of CO has been hypothesized.

Smartphone-based 3D-printed electrochemiluminescence enzyme biosensor for reagentless glucose quantification in real matrices.

Three-dimensional (3D) printed electrochemical devices are increasingly used in point-of-need and point-of-care testing. They show several advantages such as simple fabrication, low cost, fast response, and excellent selectivity and sensitivity in small sample volumes. However, there are only a few examples of analytical devices combining 3D-printed electrodes with electrochemiluminescence (ECL) detection, an electrochemical detection principle widely employed in clinical chemistry analysis. Herein, a portable, 3D-printed miniaturized ECL biosensor for glucose detection has been developed, based on the luminol/H2O2 ECL system and employing a two-electrode configuration with carbon black-doped polylactic acid (PLA) electrodes. The ECL emission is obtained by means of a 1.5V AA alkaline battery and detected using a smartphone camera, thus providing easy portability of the analytical platform. The ECL system was successfully applied for sensing H2O2 and, upon coupling the luminol/H2O2 system with the enzyme glucose oxidase, for glucose detection. The incorporation of luminol and glucose oxidase in an agarose hydrogel matrix allowed to produce ECL devices preloaded with the reagents required for the assay, so that the analysis only required sample addition. The ECL biosensor showed an excellent ability to detect glucose up to 5 mmol L-1, with a limit of detection of 60 µmol L-1. The biosensor was also used to analyse real samples (i.e., glucose saline solutions and artificial serum samples) with satisfactory results, thus suggesting its suitability for point-of-care analysis. Coupling with other oxidases could further extend the applicability of this analytical platform.

Standardising policy and technology responses in the immediate aftermath of a pandemic: a comparative and conceptual framework.

BACKGROUND: The initial policy response to the COVID-19 pandemic has differed widely across countries. Such variability in government interventions has made it difficult for policymakers and health research systems to compare what has happened and the effectiveness of interventions across nations. Timely information and analysis are crucial to addressing the lag between the pandemic and government responses to implement targeted interventions to alleviate the impact of the pandemic. METHODS: To examine the effect government interventions and technological responses have on epidemiological and economic outcomes, this policy paper proposes a conceptual framework that provides a qualitative taxonomy of government policy directives implemented in the immediate aftermath of a pandemic announcement and before vaccines are implementable. This framework assigns a gradient indicating the intensity and extent of the policy measures and applies the gradient to four countries that share similar institutional features but different COVID-19 experiences: Italy, New Zealand, the United Kingdom and the United States of America. RESULTS: Using the categorisation framework allows qualitative information to be presented, and more specifically the gradient can show the dynamic impact of policy interventions on specific outcomes. We have observed that the policy categorisation described here can be used by decision-makers to examine the impacts of major viral outbreaks such as SARS-CoV-2 on health and economic outcomes over time. The framework allows for a visualisation of the frequency and comparison of dominant policies and provides a conceptual tool to assess how dominant interventions (and innovations) affect different sets of health and non-health related outcomes during the response phase to the pandemic. CONCLUSIONS: Policymakers and health researchers should converge toward an optimal set of policy interventions to minimize the costs of the pandemic (i.e., health and economic), and facilitate coordination across governance levels before effective vaccines are produced. The proposed framework provides a useful tool to direct health research system resources and build a policy benchmark for future viral outbreaks where vaccines are not readily available.

Electrochemiluminescence Amplification in Bead-Based Assays Induced by a Freely Diffusing Iridium(III) Complex.

Heterogeneous electrochemiluminescence (ECL) assays employing tri-n-propylamine as a co-reactant and a tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) derivative as an emissive label are integral to the majority of academic and commercial applications of ECL sensing. This model system is an active research area and constitutes the basis of successfully commercialized bead-based ECL immunoassays. Herein, we propose a novel approach to the enhancement of such conventional ECL assays via the incorporation of a second metal coordination complex, [Ir(sppy)3]3- (where sppy = 5'-sulfo-2-phenylpyridinato-C2,N), to the experimental system. By employing ECL microscopy, we are able to map the spatial distribution of ECL emission at the surface of the bead, from [Ru(bpy)3]2+ labels, and solution-phase emission, from [Ir(sppy)3]3-. The developed [Ir(sppy)3]3--mediated enhancement approach elicited a significant improvement (70.9-fold at 0.9 V and 2.9-fold at 1.2 V vs Ag/AgCl) of the ECL signal from [Ru(bpy)3]2+ labels immobilized on the surface of a polystyrene bead. This dramatic enhancement in ECL signal, particularly at low oxidation potentials, has important implications for the improvement of existing heterogeneous ECL assays and ECL-based microscopy, by amplifying the signal, opening new bioanalytical detection schemes, and reducing both electrode surface passivation and deleterious side reactions.