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Hyperuricemia is a common metabolic disorder and has become a global health concern. This study investigated the association between DNA methylation (DNAm) and serum uric acid (SUA) by conducting an epigenomewide association study (EWAS) in Chinese monozygotic (MZ) twins. Genomewide DNAm of 50 MZ twin pairs was profiled using the Infinium MethylationEPIC v2.0 BeadChip (935K). Generalized estimating equations (GEE) were used to examine the association between DNAm and SUA. Causal relationships between DNAm and SUA were assessed using ICE FALCON approach. Associations between mRNA expression and SUA were further assessed. Finally, candidate genes identified through epigenomewide association study (EWAS), causal inference, and gene expression analyses were validated in a longitudinal twin study. We identified 70 CpGs, mapping to genes such as DOK6 and NGLY1, significantly associated with SUA (Bonferroni correction p < 5.8 × 10−8). Causal analyses revealed one CpG with a causal effect of DNAm on SUA, 22 CpGs with causal effects of SUA on DNAm, and 33 CpGs showing bidirectional causality. Eleven genes displayed expression levels associated with SUA. DOK6, NGLY1, PKM, and SLC44A1 were selected as candidate genes, all of which showed unidirectional causal effect of SUA on DNAm. In the longitudinal analysis, baseline SUA levels (2012–13) were associated with subsequent DNAm levels in DOK6 and NGLY1 genes (2023–24). In conclusion, we found that SUA levels may influence DNAm variations, particularly at CpG loci within the DOK6 and NGLY1 genes. These findings provide key clues for future investigations into the mechanisms linking SUA with its epigenetic regulatory pathways.
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
This chapter operates in four main movements. First, it presents the Vineyard region: its geographical features, its political organisation, its demography and the inhabitants, and a few relevant facts about its cultural history that help situate its current transformation. Second, it presents the genesis of the new ‘medico-social plan’ that frames the policies of housing and ageing in the region and thus reshapes the landscape of care. Third, it retraces the movements of its recent evolution, from its planning to its implementations, with its various setbacks. The dialogical position of the researchers, and their potential role in these changes, are finally discussed. A short synthesis closes the chapter.
Nutrition has long been investigated with respect to its influence on human health. With the availability of various omics data, such as metagenomics and metabolomics, novel insights have been obtained into the influence of nutrition, particularly concerning the gut microbiome. The gut microbiome plays an important role in the breakdown of food-derived compounds and in producing essential bioactive metabolites required for human health. However, this wealth of information made the interactions between nutrition and human health increasingly intricate, and unravelling these links is complex. This review covers the concepts of genome-scale metabolic modelling as a tool to understand the links between nutrition, the gut microbiome and human metabolism and its applications. Genome-scale metabolic modelling treats metabolism as a mathematical problem which was used to develop models of human metabolism that incorporate physiology and organ-specific metabolism, known as whole-body metabolic models (WBMs). WBMs can incorporate physiological data, such as sex, weight, and body fat percentage, as well as nutrition in the form of its metabolite constituents. Finally, the gut microbiome can also be incorporated through a mathematical representation of the species present, based on stool metagenomics. WBMs have already been applied to understand gut microbiome–host co-metabolism in various non-communicable diseases. However, challenges remain, as metabolites measured in food items in public databases typically cover only common metabolites, and engagement with end-users such as nutritionists and policymakers is limited. Nevertheless, WBMs represent a promising step towards digital metabolic twins and thus personalised nutrition and medicine.
In this chapter, the lives of persons are put in dialogue with the transformation of the Vineyard region, thus highlighting complex transactions. How did changes in policies affect daily interactions in which older persons live, or the possibilities open to them when experiencing ruptures? How could they, in turn, draw on their experience to participate in daily arrangements or social transformations? And finally, what does it mean to be involved, as researchers, in some of these dynamics? This chapter reflects on the dialogical case study perspective chosen to approach ageing in the Vineyard region. It first examines how propositions, voices or perspectives emitted sociogenetically, shape or enter in dialogue at the other levels, and how ontogenetic or microgenetic dynamics are expressing or shaped by other dynamics. It then focuses on dialogues, misunderstandings, blind spots and tensions in such a complex case. Finally, it shows how, as researchers, we participated in this regional dialogue via an art-based method – theatre – that could be seen as a dialogical catalyst.
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Patients with hypoplastic left heart syndrome who develop a restrictive atrial septum prenatally have higher rates of postnatal mortality compared to those without atrial restriction. It is not understood whether the gestational age at which restriction becomes apparent echocardiographically impacts clinical outcomes.
Methods:
A single-centre, retrospective cohort study was performed, including 196 patients with hypoplastic left heart syndrome from 2008 to 2022. A restrictive atrial septum was diagnosed based on fetal echocardiographic findings of an intact atrial septum, antegrade:retrograde pulmonary vein Doppler velocity time integral ratio <3, and/or the presence of a decompressing vein. Patients were grouped as follows: 1. Without Restriction, 2. Early Restriction (<30 weeks’ gestation), and 3. Late Restriction (≥30 weeks’ gestation), based on the gestational age at which diagnostic criteria for restriction were met. Comparative postnatal overall survival and transplant-free survival analyses were performed using the Kaplan–Meier method.
Results:
Overall mortality rates were higher in the Early group (62%, n = 13) compared to the Late group (29%, n = 7) and the group without atrial restriction (40%). Similarly, transplant rates were higher in the Early group (23%) compared to the Late group (14%) and those without restriction (14%). Overall survival and transplant-free survival were not statistically different among the groups.
Conclusions:
While not statistically significant in this cohort with a small number of patients with atrial restriction, our data suggest that patients with hypoplastic left heart syndrome who meet diagnostic criteria for atrial restriction later in gestation may have outcomes more similar to those without atrial restriction.
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Chapter 3.1 draws out insights into the way primary care is paid. Primary care delivers first-contact access to health services and seeks to coordinate care. It is paid for in different ways in different settings: through salary, capitation (a fixed payment per enlisted patient), fee for service, pay for performance or blended payments that combine two or more of these methods. Key learning includes that
The way health systems pay for primary care can incentivize treatment that supports wider health systems’ goals, most particularly by
– Reducing avoidable referrals to secondary care, improving efficiency and reducing waste and
– Encouraging adherence to evidence-based clinical guidelines, enhancing quality.
Pay for performance is often used to improve quality but the evidence on how effective it is, is mixed. If performance measures are not carefully designed to be context-specific and adjust for risk appropriately, they can create unintended barriers to and inequalities in access.
The design of primary care payment models needs to be ‘holistic’, to consider the goals of the health system and to underpin quality, access and efficiency.
Over the years, and at the margin of psychology, there have been interesting and original lines of reflections on ageing based on careful observations of older people’s lives in their environment. First, the environment came to the fore in approaches developed in dialogue with geography, which started to apprehend it as a landscape of care. Second, ethnographies of ageing gave in-depth understanding of development in age in more or less supportive, more or less formal environments. Third, psychoanalysis developed its reflection on ageing as it saw its steady change. It has theorised the specificities of the ageing psyche, while showing its multiple determinations. Put together, these three lines of studies pave the way for a rich, case-study based approach to development in older age, where people are understood as deeply related to the evolving environments in which they live.
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Chapter 3.3 examines informal payments. Informal payments are unsanctioned, unregulated payments made out-of-pocket by patients directly to their health care provider for services that are covered by third party purchasers. They are not recorded in routine administrative databases but can be captured in surveys, although they are usually underreported. Key learning includes that
Informal payments (IPs) reduce access to health care and financial protection. They can undermine population health and reduce trust in providers and governments in the long run.
IPs often stem from unmet desire for safe, timely or high-quality care and imply a mismatch between supply, demand and pricing in the formal health care payment system. When formal system payments are felt to be inadequate, IPs may also be used to express gratitude to providers.
Settings with low physician density and / or where the share of GDP spent on health care is low, tend to have higher levels of IPs.
IPs are also associated with settings with high reliance on formal out-of-pocket payments (user charges).
Reducing or ending IPs is difficult and requires a combination of specific, targeted measures and broad health systems reforms that address underlying causes.
The policy measures that may reduce IPs include
– Formalizing out-of-pocket payments, with exemptions to protect vulnerable populations
– Making clear and explicit what the health care benefits package covers
– Better monitoring and enforcement of rules and penalties
– Maintaining and expanding publicly-financed statutory coverage.
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Chapter 1.1 discusses the use of taxes and social health insurance contributions. A key objective of health financing is to redistribute financial resources from the healthy to the sick and from the well-off to the poor. This can be best achieved through compulsory prepayment mechanisms like taxes and social contributions. Key learning includes that
A high reliance on public revenue raising instruments (taxes and/or social health insurance) is essential to progress towards universal health coverage.
Large informal economies and poor governance can make collecting public revenues difficult.
Health financing systems have to be able to adapt to
– Offset challenges to the revenue base such as economic decline, low levels of economic development or a preponderance of informal employment or economic activity and
– Meet increasing health care demands which grow with rising expectations and population.
The traditional distinction between health systems that rely on general taxation (Beveridge or NHS systems) and social insurance contributions (Bismarck or SHI systems) has blurred with time.
Health systems increasingly rely on a diverse mix of revenue raising instruments to finance health care.
There is a growing focus on de-linking employment from entitlement to services in historically SHI-based systems and on emphasizing general taxation as a preferred source of revenues.
This introductory chapter presents the paradoxical status of ageing today: most people wish to live long, yet nobody really wants to get old… Ageing still appears as a scary, unknown country. The present book, concluding almost ten years of research on ageing, aspires to bring a fresh look on what becoming older may entail. It has a double aim. First, as a basic goal, it proposes a new theory of psychological development in older age. Second, it highlights the importance of the environments in which people age, and the role of well-thought-out policies to support development with age; it has thus a more applied goal. This introductory chapter then presents the outline of the volume.
Edited by
Jonathan Cylus, European Observatory on Health Systems and Policies,Rebecca Forman, European Observatory on Health Systems and Policies,Nathan Shuftan, Technische Universität Berlin,Elias Mossialos, London School of Economics and Political Science,Peter C. Smith, Imperial College of Science, Technology and Medicine, London
Health financing is a key component of any health system, but its role is more complex than simply raising and spending money on health. It is a crucial determinant of the overall performance of the health system, defining, among other things, how much money is available to be spent on health and who pays for it, who gets to benefit fromthose financial resources, what services that money can purchase and who ultimately receives resources from the health system as income. Without careful attention to the way health financing systems are designed, incentives for providers or patients can bemisaligned with policy goals, leading to poor health outcomes, financial hardship for users of health care, wasted resources, failure to address inequalities and disruption of countries’ progress towards universal health coverage (UHC) (Box 0.2.1).