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Abstract Background Severe fatigue is a common symptom for people with visual impairment, with a detrimental effect on emotional functioning, cognition, work capacity and activities of daily living. A previous study found that depression was one of the most important determinants of fatigue, but less is known about disease-specific factors in this patient population. This study aimed to explore the association between visual impairment severity and fatigue in adults with low vision, both directly and indirectly, with vision-specific factors and depression as potential mediators. Methods Cross-sectional data were collected from 220 Dutch low vision service patients by telephone interviews. Fatigue was defined as a latent variable by severity and impact on daily life. Potential mediators included vision-related symptoms, adaptation to vision loss and depression. Hypothesized structural equation models were constructed in Mplus to test (in)direct effects of visual impairment severity (mild/moderate, severe, blindness) on fatigue through above mentioned variables. Results The final model explained 60% of fatigue variance and revealed a significant total effect of visual impairment severity on fatigue. Patients with severe visual impairment (reference group) had significantly higher fatigue symptoms compared to those with mild/moderate visual impairment (β = -0.50, 95% bias-corrected confidence interval [BC CI] [-0.86, -0.16]) and those with blindness (β = -0.44, 95% BC CI [-0.80, -0.07]). Eye strain & light disturbance, depression and vision-related mobility mediated the fatigue difference between the severe and mild/moderate visual impairment categories. The fatigue difference between the severe visual impairment and blindness categories was solely explained by eye strain & light disturbance. Moreover, depressive symptoms (β = 0.65, p

Abstract Background Genetic and environmental factors play a role in the development of COPD. The epigenome, and more specifically DNA methylation, is recognized as important link between these factors. We postulate that DNA methylation is one of the routes by which cigarette smoke influences the development of COPD. In this study, we aim to identify CpG-sites that are associated with cigarette smoke exposure and lung function levels in whole blood and validate these CpG-sites in lung tissue. Methods The association between pack years and DNA methylation was studied genome-wide in 658 current smokers with >5 pack years using robust linear regression analysis. Using mediation analysis, we subsequently selected the CpG-sites that were also associated with lung function levels. Significant CpG-sites were validated in lung tissue with pyrosequencing and expression quantitative trait methylation (eQTM) analysis was performed to investigate the association between DNA methylation and gene expression. Results 15 CpG-sites were significantly associated with pack years and 10 of these were additionally associated with lung function levels. We validated 5 CpG-sites in lung tissue and found several associations between DNA methylation and gene expression. Conclusion This study is the first to validate a panel of CpG-sites that are associated with cigarette smoking and lung function levels in whole blood in the tissue of interest: lung tissue.

Abstract Background Publicly funded healthcare forms an intricate part of government spending in most Organisation for Economic Co-operation and Development (OECD) countries, because of its reliance on entitlements and dedicated revenue streams. The impact of budgetary rules and procedures on publicly funded health care might thus be different from other spending categories. In this study we focus on the potential of fiscal rules to contain these costs and their design features. Methods We assess the relationship between fiscal rules and the level of public health care expenditure of 32 (OECD) countries between 1985 and 2014. Our dataset consists of health care expenditure data of the OECD and data on fiscal rules of the International Monetary Fund (IMF) for that same period. Through a multivariate regression analysis, we estimate the association between fiscal rules and its subcategories and inflation adjusted public health care expenditure. We control for population, Gross Domestic Product (GDP), debt and whether countries received an IMF bailout for the specific period. In all our regressions we include country and year fixed effects. Results The presence of a fiscal rule on average is associated with a 3 % reduction of public health care expenditure. Supranational balanced budget rules are associated with some 8 % lower expenditure. Health service provision-oriented countries with more passive purchasing structures seem less capable of containing costs through fiscal rules. Fiscal rules demonstrate lagged effectiveness; the potential for expenditure reduction increases after one and two years of fiscal rule implementation. Finally, we find evidence that fiscal frameworks that incorporate multi-year expenditure ceilings show additional potential for cost control. Conclusions Our study shows that there seems a clear relationship between the potential of fiscal rules and budgeting health expenses. Using fiscal rules to contain the level of health care expenditure can thus be a necessary precondition for successful strategies for cost control.

Abstract Background Previous research has provided evidence for the link between psychological processes and psychophysiological health outcomes. Psychological interventions, such as face-to-face or online cognitive behavioral therapy (CBT) and serious games aimed at improving health, have shown promising results in promoting health outcomes. Few studies so far, however, have examined whether Internet-based CBT combined with serious gaming elements is effective in modulating health outcomes. Moreover, studies often did not incorporate psychophysiological or immunological challenges in order to gain insight into physiological responses to real-life challenges after psychological interventions. The overall aim of this study is to investigate the effects of a psychological intervention on self-reported and physiological health outcomes in response to immune and psychophysiological challenges. Methods/design In a randomized controlled trial, 60 healthy men are randomly assigned to either an experimental condition, receiving guided Internet-based (e-health) CBT combined with health-related serious gaming elements for 6 weeks, or a control condition receiving no intervention. After the psychological intervention, self-reported vitality is measured, and participants are given an immunological challenge in the form of a Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccination. One day after the vaccination, participants are asked to perform several psychophysiological tasks in order to explore the effects of the psychological intervention on participants’ stress response following the immune challenge. To assess the delayed effects of vaccination on self-reported and physiological health outcomes, a follow-up visit is planned 4 weeks later. Total study duration is approximately 14 weeks. The primary outcome measure is self-reported vitality measured directly after the intervention. Secondary outcome measures include inflammatory and endocrine markers, as well as psychophysiological measures of heart rate and skin conductance in response to the psychophysiological tasks after the BCG vaccination. Discussion The innovative design features of this study – e.g., combining guided e-health CBT with health-related serious gaming elements and incorporating immunological and psychophysiological challenges – will provide valuable information on the effects of a psychological intervention on both self-reported and physiological health outcomes. This study will offer further insights into the mechanisms underlying the link between psychological factors and health outcomes and is anticipated to contribute to the optimization of health care strategies. Trial registration Nederlands Trial Register, NTR5610 . Registered on 4 January 2016.