Estimating the burden of underdiagnosis within England: A modelling study of linked primary care data.

Introduction: Undiagnosed chronic disease has serious health consequences, and variation in rates of underdiagnosis between populations can contribute to health inequalities. We aimed to estimate the level of undiagnosed disease of 11 common conditions and its variation across sociodemographic characteristics and regions in England.

Methods: We used linked primary care, hospital and mortality data on approximately 1.

Primer on Health Equity Research in Health Economics and Outcomes Research: An ISPOR Special Interest Group Report.

Objectives: Disparities in health and healthcare between more and less socially advantaged groups are pervasive, multidimensional, and far-reaching. The material and social conditions in which people are born, grow, work, live, and age are systematically associated with their health and with the volume, quality, and outcomes of care received by the vast majority of the general population, as well as by specific marginalized populations. The field of health economics and outcomes research (HEOR) has an important role in supporting health equity goals.

Does household income predict health and educational outcomes in childhood better than neighbourhood deprivation?

Background: Public health research and prevention policies often use the small area Index of Multiple Deprivation (IMD) at neighbourhood level to proxy individual socio-economic status because it is readily available. We investigated what household income adds to IMD in early childhood for predicting adverse health in adolescence.

Methods: Using data from the Millennium Cohort Study, we analysed IMD and self-reported equivalised household income (ages 0-5) to predict outcomes at age 17: poor academic achievement, psychological distress, poor health, smoking, and obesity.

Inequalities in the prevalence recording of 205 chronic conditions recorded in primary and secondary care for 12 million patients in the English National Health Service.

Background: Understanding the prevalence of diseases and where it is detected and recorded in healthcare settings is important for planning effective prevention and care provision. We examined inequalities in the prevalence of 205 chronic conditions and in the care setting where the related diagnoses were recorded in the English National Health Service.

Methods: We used data from the Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics for 12.

Aversion to income, ethnic, and geographic related health inequality: Evidence from Australia.

This study investigated the Australian general public's views on trade-offs between reducing health inequalities and improving total health. It elicited relative equity weights, comparing inequalities in life expectancy at birth across three equity-relevant dimensions: income (comparing poorest versus richest fifth), ethnic (comparing Indigenous versus non-Indigenous), and geographic (comparing rural/remote versus major cities). A benefit trade-off exercise was administered via online survey to a sample of Australian adults (n = 3105) using quota sampling to ensure population representativeness across key demographic variables (age, gender, state of residence, household income and education level).

Core Modifications of GSK3335103 toward Orally Bioavailable αβ Inhibitors with Improved Synthetic Tractability.

The αβ integrin has been identified as a target for the treatment of fibrotic diseases, based on the role it has in activating TGF-β, a protein implicated in the pathogenesis of fibrosis. However, the development of orally bioavailable αβ inhibitors has proven challenging due to the zwitterionic pharmacophore required to bind to the RGD binding site. This work describes the design and development of a novel, orally bioavailable series of αβ inhibitors, developing on two previously published αβ inhibitors, GSK3008348 and GSK3335103.

Capturing the Value of Vaccination within Health Technology Assessment and Health Economics-Practical Considerations for Expanding Valuation by Including Key Concepts.

Following the development of a value of vaccination (VoV) framework for health technology assessment/cost-effectiveness analysis (HTA/CEA), and identification of three vaccination benefits for near-term inclusion in HTA/CEA, this final paper provides decision makers with methods and examples to consider benefits of health systems strengthening (HSS), equity, and macroeconomic gains. Expert working groups, targeted literature reviews, and case studies were used. Opportunity cost methods were applied for HSS benefits of rotavirus vaccination.

Are local public expenditure reductions associated with increases in inequality in emergency hospitalisation? Time-series analysis of English local authorities from 2010 to 2017.

Background: Reductions in local government funding implemented in 2010 due to austerity policies have been associated with worsening socioeconomic inequalities in mortality. Less is known about the relationship of these reductions with healthcare inequalities; therefore, we investigated whether areas with greater reductions in local government funding had greater increases in socioeconomic inequalities in emergency admissions.

Methods: We examined inequalities between English local authority districts (LADs) using a fixed-effects linear regression to estimate the association between LAD expenditure reductions, their level of deprivation using the Index of Multiple Deprivation (IMD) and average rates of (all and avoidable) emergency admissions for the years 2010-2017.

Estimating the Lifetime Costs and Benefits of the Incredible Years Teacher Classroom Management Intervention Using Data From 30 Months Follow-Up of the Supporting Teachers and childRen in Schools Trial.

Objectives: The Incredible Years Teacher® Classroom Management (IY-TCM) intervention is associated with short-term improvements in mental health difficulties in young people. The aim was to estimate the long-term impact and cost-effectiveness of the IY-TCM intervention compared with no intervention.

Methods: An existing health economic model (LifeSim 1.

Potentially avoidable hospitalizations and socioeconomic status in Switzerland: A small area-level analysis.

The Swiss healthcare system is well known for the quality of its healthcare and population health but also for its high cost, particularly regarding out-of-pocket expenses. We conduct the first national study on the association between socioeconomic status and access to community-based ambulatory care (CBAC). We analyze administrative and hospital discharge data at the small area level over a four-year time period (2014 - 2017).

Epichloë fungal endophyte interactions in perennial ryegrass (Lolium perenne L.) modified to accumulate foliar lipids for increased energy density.

Background: Commercial cultivars of perennial ryegrass infected with selected Epichloë fungal endophytes are highly desirable in certain pastures as the resulting mutualistic association has the capacity to confer agronomic benefits (such as invertebrate pest deterrence) largely due to fungal produced secondary metabolites (e.g., alkaloids).

Small Molecule Ligands of the BET-like Bromodomain, BRD3, Affect Survival, Oviposition, and Development.

Schistosomiasis is a disease affecting >200 million people worldwide, but its treatment relies on a single agent, praziquantel. To investigate new avenues for schistosomiasis control, we have conducted the first systematic analysis of bromodomain-containing proteins (BCPs) in a causative species, . Having identified 29 putative bromodomains (BRDs) in 22 proteins, we selected BRD3, a tandem BRD-containing BCP that shows high similarity to the human bromodomain and extra terminal domain (BET) family, for further studies.

Structure-Guided Design of a Domain-Selective Bromodomain and Extra Terminal N-Terminal Bromodomain Chemical Probe.

Small-molecule-mediated disruption of the protein-protein interactions between acetylated histone tails and the tandem bromodomains of the bromodomain and extra-terminal (BET) family of proteins is an important mechanism of action for the potential modulation of immuno-inflammatory and oncology disease. High-quality chemical probes have proven invaluable in elucidating profound BET bromodomain biology, with seminal publications of both pan- and domain-selective BET family bromodomain inhibitors enabling academic and industrial research. To enrich the toolbox of structurally differentiated N-terminal bromodomain (BD1) BET family chemical probes, this work describes an analysis of the GSK BRD4 bromodomain data set through a lipophilic efficiency lens, which enabled identification of a BD1 domain-biased benzimidazole series.

Using administrative data to evaluate national policy impacts on child and maternal health: a research framework from the Maternal and Child Health Network (MatCHNet).

Reducing health inequalities by addressing the social circumstances in which children are conceived and raised is a societal priority. Early interventions are key to improving outcomes in childhood and long-term into adulthood. Across the UK nations, there is strong political commitment to invest in the early years.

Meta-evaluation of a whole systems programme, ActEarly: A study protocol.

Introduction: Living in an area with high levels of child poverty predisposes children to poorer mental and physical health. ActEarly is a 5-year research programme that comprises a large number of interventions (>20) with citizen science and co-production embedded. It aims to improve the health and well-being of children and families living in two areas of the UK with high levels of deprivation; Bradford in West Yorkshire, and the London Borough of Tower Hamlets.

Guidance on the use of complex systems models for economic evaluations of public health interventions.

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis.

Identifying opportunities for upstream evaluations relevant to child and maternal health: a UK policy-mapping review.

Objective: Interventions to tackle the social determinants of health can improve outcomes during pregnancy and early childhood, leading to better health across the life course. Variation in content, timing and implementation of policies across the 4 UK nations allows for evaluation. We conducted a policy-mapping review (1981-2021) to identify relevant UK early years policies across the social determinants of health framework, and determine suitable candidates for evaluation using administrative data.

Clustering of adverse health and educational outcomes in adolescence following early childhood disadvantage: population-based retrospective UK cohort study.

Background: Disadvantage in early childhood (ages 0-5 years) is associated with worse health and educational outcomes in adolescence. Evidence on the clustering of these adverse outcomes by household income is scarce in the generation of adolescents born since the turn of the millennium. We aimed to describe the association between household income in early childhood and physical health, psychological distress, smoking behaviour, obesity, and educational outcomes at age 17 years, including the patterning and clustering of these five outcomes by income quintiles.

Understanding the relationship between income and mental health among 16- to 24-year-olds: Analysis of 10 waves (2009-2020) of Understanding Society to enable modelling of income interventions.

A substantial body of evidence suggests that young people, including those at the crucial transition points between 16 and 24, now face severe mental health challenges. In this article, we analyse data from 10 waves of a major UK longitudinal household cohort study, Understanding Society, to examine the relationship between income and anxiety and depression among 16- to 24-year-olds. Using random effects logistic regression (Model 1) allowing for whether the individual was depressed in the previous period as well as sex, age, ethnicity, whether the individual was born in the UK, region, rurality, highest qualification, marital status, employment status and attrition, we find a significant and inversely monotonic adjusted association between average net equivalised household income quintiles and clinical threshold levels of depressive symptoms SF-12 Mental Component Summary (MCS score ≤45.

Identification and Optimization of a Ligand-Efficient Benzoazepinone Bromodomain and Extra Terminal (BET) Family Acetyl-Lysine Mimetic into the Oral Candidate Quality Molecule I-BET432.

The bromodomain and extra terminal (BET) family of proteins are an integral part of human epigenome regulation, the dysregulation of which is implicated in multiple oncology and inflammatory diseases. Disrupting the BET family bromodomain acetyl-lysine (KAc) histone protein-protein interaction with small-molecule KAc mimetics has proven to be a disease-relevant mechanism of action, and multiple molecules are currently undergoing oncology clinical trials. This work describes an efficiency analysis of published GSK pan-BET bromodomain inhibitors, which drove a strategic choice to focus on the identification of a ligand-efficient KAc mimetic with the hypothesis that lipophilic efficiency could be drastically improved during optimization.

The Impact of Funding Inpatient Treatments for COVID-19 on Health Equity in the United States: A Distributional Cost-Effectiveness Analysis.

Objectives: We conducted a distributional cost-effectiveness analysis (DCEA) to evaluate how Medicare funding of inpatient COVID-19 treatments affected health equity in the United States.

Methods: A DCEA, based on an existing cost-effectiveness analysis model, was conducted from the perspective of a single US payer, Medicare. The US population was divided based on race and ethnicity (Hispanic, non-Hispanic black, and non-Hispanic white) and county-level social vulnerability index (5 quintile groups) into 15 equity-relevant subgroups.

Cost of health inequality to the NHS in Wales.

Background: Forty years from the seminal work of Welsh GP Julian Tudor Hart on the Inverse Care Law, inequalities in health and healthcare remain deeply embedded in Wales. There is a wider gap (over 17 years) in healthy life expectancy between people living in the most and least deprived neighborhoods in Wales. This health inequality is reflected in additional healthcare use.

An alternative angiosperm DGAT1 topology and potential motifs in the N-terminus.

The highly variable cytoplasmic N-terminus of the plant diacylglycerol acyltransferase 1 (DGAT1) has been shown to have roles in oligomerization as well as allostery; however, the biological significance of the variation within this region is not understood. Comparing the coding sequences over the variable N-termini revealed the Poaceae DGAT1s contain relatively high GC compositional gradients as well as numerous direct and inverted repeats in this region. Using a variety of reciprocal chimeric DGAT1s from angiosperms we show that related N-termini had similar effects (positive or negative) on the accumulation of the recombinant protein in .

Comparing healthcare quality: A common framework for both ordinal and cardinal data with an application to primary care variation in England.

The paper proposes a framework for comparing the quality of healthcare providers and assessing the variation in quality between them, which is directly applicable to both ordinal and cardinal quality data on a comparable basis. The resultant measures are sensitive to the full distribution of quality scores for each provider, not just the mean or the proportion meeting some binary quality threshold, thereby making full use of the multicategory response data increasingly available from patient experience surveys. The measures can also be standardized for factors such as age, sex, ethnicity, health and deprivation using a distribution regression model.