New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.
MULTIFILE
Background: Shared decision-making (SDM) is often considered the ideal for decision-making in oncology. Views of specific groups such as ethnic minorities have seldom been considered in its development. Aim: In this study we seek to assess in oncology if there is a need for adaptation of the current SDM model to ethnic minorities and to formulate possible adjustments. Design: This study is embedded in empirical bioethics, an interdisciplinary approach integrating empirical data with ethical reasoning to formulate normative conclusions regarding a practice. For the empirical social scientific part, a cross-sectional qualitative study will be conducted; for the ethical reflection the Reflective Equilibrium will be used to develop a coherent view on the application of SDM among ethnic minorities in oncology. Method: Semi-structured interviews combined with visual methods (timelines and relational maps) will be held with healthcare professionals (HCPs), ethnic minority patients, and their relatives to identify values steering the behavior of these actors in SDM. In addition, focus groups (FGs) will be held with ethnic minority community members to identify value structures at the group level. Respondents will be recruited through organizations with access to ethnic minorities and collaborating hospitals. Data will be analyzed using a reflexive thematic analysis through the lens of Schwartz’s value theory. The results of the empirical phase will be included in the RE to formulate possible adjustments of the SDM model, if needed. Discussion: The integration of empirical data with ethical reflection is an innovative method in decision-making. This method enables a systematic and profound assessment of the need for adaptation of SDM and the formulation of theoretically and empirically based suggestions for adaptations of the model. Findings of this study may enrich the SDM model.
PURPOSE: To investigate the reliability and validity of the SQUASH physical activity (PA) questionnaire in a multi-ethnic population living in the Netherlands.METHODS: We included participants from the HELIUS study, a population-based cohort study. In this study we included Dutch (n = 114), Turkish (n = 88), Moroccan (n = 74), South-Asian Surinamese (n = 98) and African Surinamese (n = 91) adults, aged 18-70 years. The SQUASH was self-administered twice to assess test-re-test reliability (mean interval 6-7 weeks) and participants wore an accelerometer and heart rate monitor (Actiheart) to enable assessment of construct validity.RESULTS: We observed low test-re-test reliability; Intra class correlation coefficients ranged from low (0.05 for moderate/high intensity PA in African Surinamese women) to acceptable (0.78 for light intensity PA in Moroccan women). The discrepancy between self-reported and measured PA differed on the basis of the intensity of activity: self-reported light intensity PA was lower than measured but self-reported moderate/high intensity PA was higher than measured, with wide limits of agreement. The discrepancy between questionnaire and Actiheart measures of moderate intensity PA did not differ between ethnic minority and Dutch participants with correction for relevant confounders. Additionally, the SQUASH overestimated the number of participants meeting the Dutch PA norm; Cohen's kappas for the agreement were poor, the highest being 0.30 in Dutch women.CONCLUSION: We found considerable variation in the test-re-test reliability and validity of self-reported PA with no consistency based on ethnic origin. Our findings imply that the SQUASH does not provide a valid basis for comparison of PA between ethnic groups.
Cities across the globe are facing population ageing, which poses many unsolved challenges. Regional, national and European research strategies (including EU4Health) have a strong relation with healthy and active ageing, and stimulate the exchange of best practices to create age-inclusive societies across the continent. Over 1500 cities joined the Global Network for Age Friendly Cities and Communities of the World Health Organization (WHO), which follow a 5-year cycle of planning, implementation and evaluation in order to achieve goals. The Hague (2015) has been an active member of the Network. In the Western Balkans, only Tuzla (2023) is a member. Both the WHO and THUAS seek further expansion of their reach and want to build capacity in the Western Balkans, which is achieved through existing contacts with Mother Teresa University. The Institute for Social Activities in Skopje see THUAS’s age-friendly actions as a stepping stone for a better understanding of ageing well in their ethnically diverse city. Organisations in bordering countries have indicated their interest to join efforts during the annual Towards Sustainable Development Conference. They seek an extension to other countries of the Western Balkans that have previously largely been left out of the European research agenda. Therefore, The Age-friendly Balkans Connected Network seeks to (1) form regional knowledge and action eco-systems through capacity-building, and (2) provide cities with an instrument for a baseline assessment of their age-friendliness. For this purpose, we use the existing Age-Friendly Cities and Communities Questionnaire that was developed at THUAS in 2020 and which has been validated in Albanian and Macedonian. The Network trusts that new national ecosystems and tools can contribute to future age-friendly actions and European grant applications. In the words of Mother Teresa (born in Skopje): “Yesterday is gone. Tomorrow has not yet come. We have only today. Let us begin.”
The increasing concentration of people in urban environments in an era of globalisation means that social, economic, and environmental resources for living and working are under pressure. Urban communities experience increased stress levels due to inadequate and overburdened infrastructure and services, challenges due to ethnic and cultural diversity, socio-economic inequalities as well as the impact of environmental degradation. For these communities to build resilience under these circumstances therefore requires a multipronged approach. The underlying question this project will answer is: “What are the key characteristics of experiencescapes that contribute to resilience-building in communities?” The project will dive into the identification of building blocks of experiencescapes and roles of relevant actors that can support communities in building resilience. Within the context of a multidisciplinary approach, this project applies a range of qualitative research methods, such as in-depth interviews, focus groups, participant observation, storytelling techniques, life stories, as well as various biometric quantitative methods, available through the experience lab of BUas. The outcome of the project will enable practitioners and researchers alike in various sectors to understand what and how they can contribute to creating an environment in which people can meaningfully interact in a way that builds resilience in communities. This outcome is communicated not only through academic publications and conference contributions, but also through public reports and a handbook for practitioners and students. These reports and handbooks support identification and application of building blocks of experiencescapes that support building resilience in communities. Finally, the knowledge generated in the project will contribute to the development of curricula of various educational programmes at Breda University of Applied Sciences by expanding the scope of experience design into the area of people-to-people relationships.
