“I wouldn't survive it, as simple as that”: Syndemic vulnerability among people living with chronic non-communicable disease during the COVID-19 pandemic

The co-occurrence of COVID-19, non-communicable diseases and socioeconomic disadvantage has been identified as creating a syndemic: a state of synergistic epidemics, occurring when co-occurring health conditions interact with social conditions to amplify the burden of disease. In this study, we use the concept of illness management work to explore the impact of the COVID-19 pandemic on the lives of people living with, often multiple, chronic health conditions in a range of social circumstances. In-depth interviews were conducted between May and July 2020 with 29 participants living in a city in North East England. Qualitative data provide unique insights for those seeking to better understand the consequences for human life and wellbeing of the interacting social, physical and psychological factors that create syndemic risks in people's lives. Among this group of people at increased vulnerability to harm from COVID-19, we find that the pandemic public health response increased the work required for condition management. Mental distress was amplified by fear of infection and by the requirements of social isolation and distancing that removed participants' usual sources of support. Social conditions, such as poor housing, low incomes and the requirement to earn a living, further amplified the work of managing everyday life and risked worsening existing mental ill health. As evidenced by the experiences reported here, the era of pandemics will require a renewed focus on the connection between health and social justice if stubborn, and worsening health and social inequalities are to be addressed or, at the very least, not increased

Socioeconomic inequalities in vaccine uptake: A global umbrella review

This global umbrella review aimed to synthesise evidence of socioeconomic inequalities in the uptake of routine vaccinations and identify the mechanisms that may contribute to the association. To our knowledge, no attempt has been made to synthesise the global body of systematic reviews across a variety of vaccines, geographical locations, and measures of SES. The inclusion criteria were as follows: studies assessing vaccination uptake according to education, income, occupation/employment, and/or area-level deprivation; any country or universally recommended routine vaccination (according to the WHO); qualitative or quantitative reviews, published 2011-present. The searches were performed in eight databases. The screening process followed PRISMA-E guidelines, each stage was performed by one reviewer, and a 10% sample checked by a second for consistency. Included reviews underwent data extraction, quality appraisal (AMSTAR-2), and narrative synthesis according to country-context. After deduplication, 9,163 reports underwent title and abstract screening, leaving 119 full texts to be assessed for eligibility. Overall, 26 studies were included in the umbrella review. Evidence for lower uptake amongst disadvantaged SES individuals was found in all 26 reviews. However, 17 reviews showed mixed results, as inverse associations were also identified (lower uptake for advantaged SES, and/or higher uptake for disadvantaged SES). Those that explored high-income countries had a greater prevalence of mixed findings than those focusing on low/middle-income countries. The two most frequently cited mechanisms were vaccination knowledge, and confidence in vaccination or vaccination providers. These mechanisms were often understood by review authors as varying by level of education. We find socioeconomic differences in routine vaccination uptake, but the association did not always follow a gradient. Whilst education may be associated with uptake globally, our study indicates that its role varies by country-context. A limitation is the overlap of some primary studies across the included systematic reviews.10.1371/journal.pone.029468

Impact of metabolic comorbidity on the association between body mass index and heatlh-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants

<p/>Background: The prevalence of obesity is rising in Scotland and globally. Overall, obesity is associated with increased morbidity, mortality and reduced health-related quality of life. Studies suggest that "healthy obesity" (obesity without metabolic comorbidity) may not be associated with morbidity or mortality. Its impact on health-related quality of life is unknown. <p/>Methods: We extracted data from the Scottish Health Survey on self-reported health-related quality of life, body mass index (BMI), demographic information and comorbidity. SF-12 responses were converted into an overall health utility score. Linear regression analyses were used to explore the association between BMI and health utility, stratified by the presence or absence of metabolic comorbidity (diabetes, hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for potential confounders (age, sex and deprivation quintile). <p/>Results: Of the 5,608 individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had metabolic comorbidity. There was an inverted U-shaped relationship whereby health utility was highest among overweight individuals and fell with increasing BMI. There was a significant interaction with metabolic comorbidity (p = 0.007). Individuals with metabolic comorbidty had lower utility scores and a steeper decline in utility with increasing BMI (morbidly obese, adjusted coefficient: -0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042, 95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). <p/>Conclusions: The adverse impact of obesity on health-related quality of life is greater among individuals with metabolic comorbidity. However, increased BMI is associated with reduced health-related quality of life even in the absence of metabolic comorbidity, casting doubt on the notion of "healthy obesity"

Transport coefficients for inelastic Maxwell mixtures

The Boltzmann equation for inelastic Maxwell models is used to determine the Navier-Stokes transport coefficients of a granular binary mixture in $d$ dimensions. The Chapman-Enskog method is applied to solve the Boltzmann equation for states near the (local) homogeneous cooling state. The mass, heat, and momentum fluxes are obtained to first order in the spatial gradients of the hydrodynamic fields, and the corresponding transport coefficients are identified. There are seven relevant transport coefficients: the mutual diffusion, the pressure diffusion, the thermal diffusion, the shear viscosity, the Dufour coefficient, the pressure energy coefficient, and the thermal conductivity. All these coefficients are {\em exactly} obtained in terms of the coefficients of restitution and the ratios of mass, concentration, and particle sizes. The results are compared with known transport coefficients of inelastic hard spheres obtained analytically in the leading Sonine approximation and by means of Monte Carlo simulations. The comparison shows a reasonably good agreement between both interaction models for not too strong dissipation, especially in the case of the transport coefficients associated with the mass flux.Comment: 9 figures, to be published in J. Stat. Phy

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

The social value of a QALY : raising the bar or barring the raise?

Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England, there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were released during a time of considerable debate about the NICE threshold, and authors with differing perspectives have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for those who conducted the research to contribute to the debate as to its implications for NICE. Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’ answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the other that greater weight could be given to QALYs gained by some groups. Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be moved up for some types of QALY and down for others. While many members of the public appear to be open to the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have any secure evidence base for introducing such a system

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al