Comparison of 4% Albumin and Ringer's Acetate on Hemodynamics in On-pump Cardiac Surgery: An Exploratory Analysis of a Randomized Clinical Trial.

OBJECTIVES: Compare hemodynamics between 4% albumin and Ringer's acetate. DESIGN: Exploratory analysis of the double-blind randomized ALBumin In Cardiac Surgery trial. SETTING: Single-center study in Helsinki University Hospital. PARTICIPANTS: We included 1,386 on-pump cardiac surgical patients. INTERVENTION: We used 4% albumin or Ringer's acetate administration for cardiopulmonary bypass priming, volume replacement intraoperatively and 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Hypotension (time-weighted average mean arterial pressure of <65 mmHg) and hyperlactatemia (time-weighted average blood lactate of >2 mmol/L) incidences were compared between trial groups in the operating room (OR), and early (0-6 hours) and late (6-24 hours) postoperatively. Associations of hypotension and hyperlactatemia with the ALBumin In Cardiac Surgery primary outcome (≥1 major adverse event [MAE]) were studied. In these time intervals, hypotension occurred in 118, 48, and 17 patients, and hyperlactatemia in 313, 131, and 83 patients. Hypotension and hyperlactatemia associated with MAE occurrence. Hypotension did not differ between the groups (albumin vs Ringer's: OR, 8.8% vs 8.5%; early postoperatively, 2.7% vs 4.2%; late postoperatively, 1.2% vs 1.3%; all p > 0.05). In the albumin group, hyperlactatemia was less frequent late postoperatively (2.9% vs 9.1%; p < 0.001), but not earlier (OR, 22.4% vs 23.6%; early postoperatively, 7.9% vs 11.0%; both p > 0.025 after Bonferroni-Holm correction). CONCLUSIONS: In on-pump cardiac surgery, hypotension and hyperlactatemia are associated with the occurrence of ≥1 MAE. Compared with Ringer's acetate, albumin did not decrease hypotension and decreased hyperlactatemia only late postoperatively. Albumin's modest hemodynamic effect is concordant with the finding of no difference in MAEs between albumin and Ringer's acetate in the ALBumin In Cardiac Surgery trial.

European Health Information Portal: a one-stop shop for health information.

BACKGROUND: Timely and high-quality population-level health information is needed to support evidence-informed decision-making, for planning and evaluation of prevention, care and cure activities as well as for research to generate new knowledge. FAIR (Findable, Accessible, Interoperable and Reusable) principles are one of the key elements supporting health research and making it more cost-effective through the reuse of already existing data. Currently, health data are in many countries dispersed and difficult to find and access. METHODS: Two EU Public Health Programmes co-funded Joint Actions, Information for Action (InfAct) and Population Health Information Research Infrastructure (PHIRI) have established a European Health Information Portal, a web-based service, to facilitate better findability, access, interoperability and reuse of existing health information. RESULTS: The European Health Information Portal (www.healthinformationportal.eu) has been established including sections on National Nodes, data sources, publications, health information projects within countries and across Europe, research networks and research infrastructures, ethical and legal issues for health information exchange and use, capacity-building activities in all areas of population health and a dedicated COVID-19 section. CONCLUSIONS: The European Health Information Portal, being a central place for a wide range of population health information from EU Member States, is an information source for researchers, policy-makers and other relevant stakeholders. It is important to ensure the sustainability of the portal, especially in light of the European Health Data Space (EHDS) Regulation proposal and its requirements regarding the secondary use of health data.

National health examination surveys; a source of critical data.

The aim of this paper is to contribute technical arguments to the debate about the importance of health examination surveys and their continued use during the post-pandemic health financing crisis, and in the context of a technological innovation boom that offers new ways of collecting and analysing individual health data (e.g. artificial intelligence). Technical considerations demonstrate that health examination surveys make an irreplaceable contribution to the local availability of primary health data that can be used in a range of further studies (e.g. normative, burden-of-disease, care cascade, cost and policy impact studies) essential for informing several phases of the health planning cycle (e.g. surveillance, prioritization, resource mobilization and policy development). Examples of the use of health examination survey data in the World Health Organization (WHO) European Region (i.e. Finland, Italy, Malta and the United Kingdom of Great Britain and Northern Ireland) and the WHO Region of the Americas (i.e. Chile, Mexico, Peru and the United States of America) are presented, and reasons why health provider-led data cannot replace health examination survey data are discussed (e.g. underestimation of morbidity and susceptibility to bias). In addition, the importance of having nationally representative random samples of the general population is highlighted and we argue that health examination surveys make a critical contribution to external quality control for a country's health system by increasing the transparency and accountability of health spending. Finally, we consider future technological advances that can improve survey fieldwork and suggest ways of ensuring health examination surveys are sustainable in low-resource settings.

Cet article a pour objet d'apporter des arguments techniques au débat sur l'importance des enquêtes de santé par examen et sur leur utilisation continue pendant la crise post-pandémique du financement de la santé et dans le contexte d'un essor de l'innovation technologique qui offre de nouvelles façons de collecter et d'analyser les données individuelles sur la santé (comme l'intelligence artificielle). Les considérations techniques démontrent que les enquêtes de santé par examen apportent une contribution irremplaçable à la disponibilité locale de données de santé primaires qui peuvent servir dans une série d'études complémentaires (telles que des études normatives, sur la charge de morbidité, la cascade des soins, les coûts et l'impact des politiques). Ces études sont essentielles pour renseigner plusieurs phases du cycle de planification sanitaire (par exemple: surveillance, priorisation, mobilisation de ressources et élaboration de politiques). Cet article présente des exemples d'utilisation des données d'enquêtes de santé par examen dans la Région OMS de l'Europe (Finlande, Italie, Malte et Royaume-Uni de Grande-Bretagne et d'Irlande du Nord) et dans la Région OMS des Amériques (Chili, États-Unis d'Amérique, Mexique et Pérou) et aborde les raisons pour lesquelles les données fournies par les prestataires de soins de santé ne peuvent pas remplacer les données d'enquêtes de santé par examen (par exemple la sous-estimation de la morbidité et la vulnérabilité aux biais). En outre, il soulignet l'importance de disposer d'échantillons aléatoires représentatifs de la population générale au niveau national, et nous soutenons que les enquêtes de santé par examen apportent une contribution essentielle au contrôle externe de la qualité du système de santé d'un pays en renforçant la transparence des dépenses de santé et l'obligation de rendre des comptes à leur sujet. Enfin, nous envisageons les futures avancées technologiques susceptibles d'améliorer le travail d'enquête sur le terrain et suggérons des moyens d'assurer la viabilité des enquêtes de santé par examen dans les environnements à faibles ressources.

El objetivo de este artículo es aportar argumentos técnicos al debate sobre la importancia de las encuestas de salud y su uso continuado durante la crisis de financiación sanitaria pospandémica y en el contexto de un auge de la innovación tecnológica que ofrece nuevas formas de recopilar y analizar datos sanitarios individuales (por ejemplo, la inteligencia artificial). Las consideraciones técnicas demuestran que las encuestas de salud contribuyen de manera insustituible a la disponibilidad local de datos sanitarios primarios que pueden utilizarse en toda una serie de estudios posteriores (por ejemplo, estudios normativos, de carga de morbilidad, de cascada asistencial, de costes y de impacto de las políticas) esenciales para fundamentar varias fases del ciclo de planificación sanitaria (por ejemplo, vigilancia, establecimiento de prioridades, movilización de recursos y elaboración de políticas). Se presentan ejemplos del uso de los datos de las encuestas de salud en la Región Europea de la Organización Mundial de la Salud (Finlandia, Italia, Malta y el Reino Unido de Gran Bretaña e Irlanda del Norte) y en la Región de las Américas de la OMS (Chile, Estados Unidos de América, México y Perú) y se analizan las razones por las que los datos obtenidos por los proveedores sanitarios no pueden sustituir a los de las encuestas de salud (por ejemplo, la subestimación de la morbilidad y la posibilidad de sesgo). Además, se destaca la importancia de contar con muestras aleatorias representativas de la población general a escala nacional y se argumenta que las encuestas de salud contribuyen de forma decisiva al control de calidad externo del sistema sanitario de un país, al aumentar la transparencia y la rendición de cuentas del gasto sanitario. Por último, se examinan los futuros avances tecnológicos que pueden mejorar el trabajo de campo de las encuestas y se sugieren métodos para garantizar que las encuestas de salud sean sostenibles en entornos con pocos recursos.

Tackling the challenge of cardiovascular diseases and diabetes across Europe: a joint action by more than 300 public health professionals. Commentary.

Cardiovascular diseases (CVD) and diabetes pose significant health challenges in Europe, affecting millions and burdening healthcare systems. The recent EU4Health Programme places reducing the burden of non-communicable diseases (NCD) at the forefront, through a Joint Action focused on CVD and diabetes (JACARDI, Joint Action on CARdiovascular diseases and DIabetes). This initiative unites 21 European countries, including Ukraine, and over 300 experts. Employing an innovative approach and standardised methodology, JACARDI implements 142 pilot projects covering the entire "patient" journey. Particular focus will be given to improvement of data availability and quality. Additionally, JACARDI will emphasise transversal and intersectional aspects, such as health equity, determinants of health, and social, cultural, and ethnic diversity, while pioneering gender-transformative leadership. Committed to evidence-based interventions, JACARDI aims to harmonise strategies and disseminate knowledge for enhanced CVD and diabetes prevention and management. The goal is to identify effective strategies for wider implementation, fostering cross-national collaboration and fortifying Europe's health resilience.

Dietary atherogenicity and thrombogenicity indexes predicting cardiovascular mortality: 50-year follow-up of the Seven Countries Study.

BACKGROUND AND AIM: To study the relationships of an Atherogenicity Index (ATI) and a Thrombogenicity Index (THI), with 50-year mortality from coronary heart disease (CHD), other heart diseases of uncertain etiology (HDUE) and cerebrovascular disease or stroke (STR), in 16 international cohorts of middle-aged men. METHODS AND RESULTS: Foods from a dietary survey in subsamples of men in each cohort of the Seven Countries Study (SCS) were chemically analyzed for several types of fatty acids that were converted into ATI and THI identifying each of 16 cohorts. Ecological correlations of the ATI and THI were calculated with the three fatal CVD conditions and with all-cause mortality at 25 and 50 years. Correlation coefficients (Rs) were positive and highly significant between ATI and THI versus CHD mortality, with levels ranging from 0.79 to 0.97, depending on the duration of follow-up and the choice of 10 or of 16 cohorts. This was not the case for HDUE and STR mortality for which Rs were variable and not significant. A strong direct association was also found with all-causes deaths at 25 and 50-years. ATI and THI were also directly related with dietary saturated fat and cholesterol levels and inversely with the Mediterranean Adequacy Index (a score identifying the Mediterranean diet). CONCLUSION: These findings indicate that CHD has a different relationship with dietary lipids intake than HDUE and STR. This suggests that HDUE and STR have different underlying pathways or are different diseases.

Work ability trends 2000-2020 and birth-cohort projections until 2040 in Finland.

Aims: To examine age-group and birth-cohort trends in perceived work ability in Finland in 2000-2020 and make projections of perceived work ability up to 2040 based on the observed birth-cohort development. Methods: Ten population-representative cross-sectional surveys conducted in Finland between 2000 and 2020 were used (overall N = 61,087, range 817-18,956). Self-reported estimates of current work ability in relation to the person's lifetime best on a scale from zero to ten (0-10) were classified into three groups: limited (0-5), intermediate (6-7), and good (8-10). Multiple imputation was used in projecting work ability. Results: Examining past trends by 5-year birth-cohorts born between 1961 and 1995 showed that work ability has declined steadily over time among older birth-cohorts, while in the two younger cohorts a stable development before 2017 and a steep decline between 2017 and 2020 was seen. Trends by 5-year age groups showed a declining trend of good work ability among 20-44-year-olds, a stable trend among 45-54-year-olds, and an improving trend among 55-year-olds and older was observed for the period 2000-2020. Among the under 55-year-olds the prevalence of good work ability ended up around 75% and at 68% among the 55-59-year-olds, 58% among the 60-69-year-olds and 49% among the 70-74-year-olds in 2020. Birth-cohort projections suggested a declining work ability in the future among all age groups included (30-74 years). By 2040, the prevalence of good work ability is projected to decline by 10 to 15 percentage points among 45-74-year-olds. Conclusions: The projections suggest declining work ability in the future. Efforts to counteract the decline in work ability are needed.

Physical activity and Physical fitness in Prediction of all-cause Mortality and Age at Death in European Extinct Cohorts of middle-aged men followed for 60 Years.

BACKGROUND: A study of the power of physical activity (Phyac) and physical fitness (Fitscore) in predicting very long-term all-cause mortality and age at death (AD) is missing. METHODS: A total of 5,482 middle-aged men were examined with measurement of several risk factors and followed for 60 years until virtual extinction of cohorts. Phyac in 3 classes was estimated from their type of work while Fitscore was derived from the linear combinations of levels of arm circumference, heart rate and vital capacity computed as a factor score by principal components analysis. Predictive power of these characteristics (adjusted for 5 traditional cardiovascular risk factors) was made by Cox models (for all-cause mortality) and multiple linear regression models (for AD). RESULTS: Single levels of the 3 indicators of fitness were highly related to the 3 levels of Phyac and of Fitscore. High levels of both Phyac and of Fitscore forced into the same models were associated with lower all-cause mortality and higher AD. Predictive power of Fitscore was systematically better than that of Phyac. Hazard ratios (high versus low) for all-cause mortality were 0.85 (Phyac) and 0.70 (Fitscore). Coefficients (all significant) were 2.25 years (Phyac) and 3.79 of AD by Fitscore. Fitscore was independently and significantly predictive of all-cause mortality for both first and second 30-year follow-up periods. CONCLUSIONS: Phyac and Fitscore are related and both showed important predictive power for all-cause mortality and AD. The role of Fitscore was more powerful and both characteristics seem to be expressions of health status.

Objectively measured physical fitness derived from linearly combined arm circumference, heart rate and vital capacity (Fitscore) may represent an improvement over classes of physical activity (Phyac) estimated from the type of work performed. What was comparatively assessed among 5,482 middle-aged men examined with measurement of several risk factors and followed for 60 years until virtual extinction of cohorts. Arm circumference, heart rate and vital capacity were highly related to the 3 levels of Phyac and of Fitscore. High levels of both Phyac and of Fitscore were associated with lower all-cause mortality and higher age at death (AD). The predictive power of Fitscore was systematically better than that of Phyac and comparing high versus low Phyac and Fitscore there was a statistically significant difference in all-cause mortality risk and AD, respectively 0.85 of hazard and 2.25 years (for Phyac) and 0.70 of hazard and 3.79 years (for Fitscore). Physical fitness is reportedly defined as the ability to carry out daily tasks with vigor and alertness, without undue fatigue and with ample energy to enjoy leisure-time pursuits and to meet unforeseen emergencies and might thus help to better assess long-term risk of all-cause mortality and higher AD when Fitscore based on arm circumference, heart rate and vital capacity are in the upper tertile. This is an improvement over Phyac that is reportedly defined as any bodily movement produced by skeletal muscles that results in energy expenditure. This study shows that Fitscore should be applied in day-to-day clinical/preventive cardiology practice.

Competing Risks of Coronary Heart Disease Mortality versus Other Causes of Death in 10 Cohorts of Middle-Aged Men of the Seven Countries Study Followed for 60 Years to Extinction.

OBJECTIVES: To assess whether competing risks help explain why regions with initially high serum cholesterol have higher mortality from coronary heart disease (CHD) and lower mortality from stroke and other major heart diseases, while the reverse is found for those with initially lower serum cholesterol. MATERIAL AND METHODS: Ten cohorts of men (N = 9063) initially aged 40-59 in six countries were examined and followed for fatal outcomes for 60 years. Major cardiovascular disease (CVD) groups were CHD, stroke, and other Heart Diseases of Uncertain Etiology (HDUE), or the combination of stroke and HDUE (STHD), along with all other causes of death. Fine-Gray competing risk analysis was applied with CHD versus all other causes of death or STHD (direct mode) and all other causes of death or STHD versus CHD (inverse mode), and the effects of 19 covariates (of which 3 references) on the cause-specific hazard of the outcomes were assessed, thus investigating potential etiologic roles. A systematic comparison with results obtained by running the Cox model in direct and inverse modes with the same end-point results was also performed and illustrated graphically. RESULTS: CHD mortality is bound to different risk factor relationships when compared with all other causes of death and with STHD. The role of serum cholesterol is crucial since, in both comparisons, by Fine-Gray, its coefficients are positive and significant for CHD and negative and significant for all other causes of death and STHD. Risk factor capabilities in specific outcome types of the CVD domain (CHD versus STHD) are different depending on the outcome types considered. Risk factor coefficients are smaller in Fine-Gray modelling and larger in the Cox model. Fine-Gray detects different risk factors whose coefficients may have opposite algebraic signs. CONCLUSIONS: This is the first report whereby a large group of risk factors are investigated in connection with life-long CVD outcomes by Fine-Gray competing risk analysis, and a systematic comparison is performed with results obtained by Cox models in both direct and inverse modes. Subtypes of CVD mortality should be summed with full awareness that some risk factors vary by pathology, and they should at least be disentangled into CHD and STHD.

Time Patterns in Internal Human Exposure Data to Bisphenols, Phthalates, DINCH, Organophosphate Flame Retardants, Cadmium and Polyaromatic Hydrocarbons in Europe.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

National Health Examination Surveys: an essential piece of the health planning puzzle.

National health examination surveys (HESs) have been developed to provide important information that cannot be obtained from other sources. A HES combines information obtained by asking participants questions with biophysical measurements taken by trained field staff. They are observational studies with the highest external validity and make specific contributions to both population (public health) and individual health. Few countries have a track record of a regular wide-ranging HES, but these are the basis of many reports and scientific papers. Despite this, little evidence about HES usefulness and impact or the factors that influence HES effectiveness have been disseminated. This paper presents examples of HES contributions to society in both Europe and the Americas. We sought information by emailing a wide list of people involved in running or using national HESs across Europe and the Americas. We asked for examples of where examination data from their HES had been used in national or regional policymaking. We found multiple examples of HES data being used for agenda-setting, including by highlighting nutritional needs and identifying underdiagnosis and poor management of certain conditions. We also found many ways in which HES have been used to monitor the impact of policies and define population norms. HES data have also been used in policy formation and implementation. HES data are influential and powerful. There is need for global support, financing and networking to transfer capacities and innovation in both fieldwork and laboratory technology.

Application of human biomonitoring data to support policy development, raise awareness and environmental public health protection among countries within the HBM4EU project.

Most countries have acknowledged the importance of assessing and quantifying their population's internal exposure from chemicals in air, water, soil, food and other consumer products due to the potential health and economic impact. Human biomonitoring (HBM) is a valuable tool which can be used to quantify such exposures and effects. Results from HBM studies can also contribute to improving public health by providing evidence of individuals' internal chemical exposure as well as data to understand the burden of disease and associated costs thereby stimulating the development and implementation of evidence-based policy. To have a holistic view on HBM data utilisation, a multi-case research approach was used to explore the use of HBM data to support national chemical regulations, protect public health and raise awareness among countries participating in the HBM4EU project. The Human Biomonitoring for Europe (HBM4EU) Initiative (https://www.hbm4eu.eu/) is a collaborative effort involving 30 countries, the European Environment Agency (EEA) and the European Commission (contracting authority) to harmonise procedures across Europe and advance research into the understanding of the health impacts of environmental chemical exposure. One of the aims of the project was to use HBM data to support evidence based chemical policy and make this information timely and directly available for policy makers and all partners. The main data source for this article was the narratives collected from 27 countries within the HBM4EU project. The countries (self-selection) were grouped into 3 categories in terms of HBM data usage either for public awareness, policy support or for the establishment HBM programme. Narratives were analysed/summarised using guidelines and templates that focused on ministries involved in or advocating for HBM; steps required to engage policy makers; barriers, drivers and opportunities in developing a HBM programme. The narratives reported the use of HBM data either for raising awareness or addressing environmental/public health issues and policy development. The ministries of Health and Environment were reported to be the most prominent entities advocating for HBM, the involvement of several authorities/institutions in the national hubs was also cited to create an avenue to interact, discuss and gain the attention of policy makers. Participating in European projects and the general population interest in HBM studies were seen as drivers and opportunities in developing HBM programmes. A key barrier that was cited by countries for establishing and sustaining national HBM programmes was funding which is mainly due to the high costs associated with the collection and chemical analysis of human samples. Although challenges and barriers still exist, most countries within Europe were already conversant with the benefits and opportunities of HBM. This article offers important insights into factors associated with the utilisation of HBM data for policy support and public awareness.

Cardiovascular Mortality in 10 Cohorts of Middle-Aged Men Followed-Up 60 Years until Extinction: The Seven Countries Study.

OBJECTIVES: To investigate mortalities from three major groups of cardiovascular diseases (CVDs) in a pooled cohort and followed up until extinction. MATERIALS AND METHODS: Ten cohorts of men (N = 9063) initially aged 40-59, in six countries, were examined and followed-up for 60 years. The major CVD groups were coronary heart disease (CHD), cerebrovascular diseases (STROKE) and other heart diseases of uncertain etiology (HDUE). RESULTS: Death rates from CHD were higher in countries with high serum cholesterol levels (USA, Finland and The Netherlands) and lower in countries with low cholesterol levels (Italy, Greece and Japan), but the opposite was observed for STROKE and HDUE, which became the most common CVD mortalities in all countries during the last 20 years of follow-up. Systolic blood pressure and smoking habits were, at an individual level, the common risk factors for the three groups of CVD conditions, while serum cholesterol level was the most common risk factor only for CHD. Overall, death rates for the pooled CVDs were 18% higher in North American and Northern European countries, while CHD rates were 57% higher in the same countries. CONCLUSIONS: Differences in lifelong CVD mortalities across different countries were smaller than expected due to the different rates of the three groups of CVD, and the indirect determinant of this seemed to be baseline serum cholesterol levels.

Partial substitution of red or processed meat with plant-based foods and the risk of type 2 diabetes.

High consumption of red and processed meat has been associated with increased type 2 diabetes (T2D) risk. These kinds of diets are also environmentally unsustainable. We examined a modeled association between a partial substitution of red meat or processed meat with plant-based foods (legumes, vegetables, fruit, cereals, or a combination of these) and T2D risk among Finnish adults. We used pooled data from five Finnish cohorts (n = 41,662, 22% women, aged ≥ 25 years, 10.9 years median follow-up with 1750 incident T2D cases). Diet was assessed by a validated food frequency questionnaire. In the substitution models, 100 g/week of red meat or 50 g/week of processed meat were substituted with similar amounts of plant-based substitutes. Cohort-specific hazard ratios (HRs) were estimated by Cox proportional hazards multivariable model and pooled using a two-staged random-effects model. We observed small, but statistically significant, reductions in T2D risk in men when red or processed meat were partially substituted with fruits (red meat: HR 0.98, 95% CI 0.97-1.00, P = 0.049, processed meat: 0.99, 0.98-1.00, P = 0.005), cereals (red meat: 0.97, 0.95-0.99, P = 0.005, processed meat: 0.99, 0.98-1.00, P = 0.004) or combination of plant-based foods (only processed meat: 0.99, 0.98-1.00, P = 0.004) but not with legumes or vegetables. The findings of women were similar but not statistically significant. Our findings suggest that even small, easily implemented, shifts towards more sustainable diets may reduce T2D risk particularly in men.

Recommendations on TNFα inhibitor biosimilar use in clinical practice: a comparison of European gastroenterology IBD guidance.

BACKGROUND: Professional associations publish guidance advising gastroenterologists on prescribing biosimilars; however, guidelines differ between countries and change over time. This study aimed to map the presence and content of guidance from European gastroenterology associations on TNFα inhibitor biosimilar use and its development over time. RESEARCH DESIGN AND METHODS: Guidelines on biosimilar prescribing from national gastroenterology associations in the European Economic Area (EEA) partnered with the European Crohn's and Colitis Organization (ECCO) were collected. Treatment guidelines and biosimilar position papers from 2010 to 2022 were included. Data were extracted using a template. RESULTS: 26 of 30 EEA countries have an ECCO-partnered gastroenterology association, of which 14 (53.8%) had national guidelines addressing biosimilars, four (15.4%) followed ECCO's position, and three (11.6%) had treatment guidelines without mentioning biosimilars. From five countries (19.2%) no guidelines were retrieved. Among 18 countries with guidance, 14 (77.8%) associations endorsed initiating biological treatment with biosimilars, and 13 (72.2%) endorsed transitioning from originator to biosimilar. Nine associations published multiple guidelines over time addressing biosimilars; overall, their positions became more encouraging. CONCLUSIONS: The majority of gastroenterology associations endorsed biosimilar use. The lack of (up-to-date) guidelines for some associations indicates an area of improvement to support biosimilar use in clinical practice.

A step towards harmonising human biomonitoring study setup on European level: Materials provided and lessons learnt in HBM4EU.

Internal exposure of the human body to potentially harmful chemical substances can be assessed by Human Biomonitoring (HBM). HBM can be used to generate conclusive data that may provide an overview of exposure levels in entire or specific population groups. This knowledge can promote the understanding of potential risks of the substances of interest or help monitoring the success of regulatory measures taken on the political level. Study planning and design are key elements of any epidemiologic study to generate reliable data. In the field of HBM, this has been done using differing approaches on various levels of population coverage so far. Comparison and combined usage of the resulting data would contribute to understanding exposure and its factors on a larger scale, however, the differences between studies make this a challenging and somewhat limited endeavour. This article presents templates for documents that are required to set up an HBM study, thus facilitating the generation of harmonised HBM data as a step towards standardisation of HBM in Europe. They are designed to be modular and adaptable to the specific needs of a single study while emphasising minimum requirements to ensure comparability. It further elaborates on the challenges encountered during the process of creating these documents during the runtime of the European Joint Programme HBM4EU in a multi-national expert team and draws up lessons learnt in the context of knowledge management.

Implementation and coordination of an ethics framework in HBM4EU - Experiences and reflections.

Human biomonitoring involves the use of human samples and data to investigate exposure to environmental chemicals and their impact on human health. HBM4EU developed a coordinated and harmonized approach involving 29 countries in Europe plus Israel. Addressing ethical issues has been an indispensable prerequisite, from the application phase, grant agreement, project performance to the closing of the project. HBM4EU has established a better understanding of the ethics in such projects and the need for a standardised way of reporting and handling of ethics and data exchange, securing compliance with ethics standards, transparency, transferability and sustainability. The main reflections were: KNOWLEDGE: Ethics awareness, norms and practices are dynamic and increased throughout the project, much learning and experience is achieved by practice and dialogue. ATTITUDE: Rules and standards were very diversely known and needed to adhere to local practices. ASSISTANCE: Good results achieved from webinars, training, help desk, and individual consultations. STANDARDISATION: Was achieved by templates and naming convention across documents. MANAGEMENT: The establishment of the SharePoint directory with uploading of all requested documents assisted collaboration and exchange. Also, a designated task for ethics within the management/coordination work package and the enthusiasm of the task leader were essential. COMPLIANCE: Some, but not all partners were very good at complying with deadlines and standards. TRANSFERABILITY AND SUSTAINABILITY: All documents are archived in the SharePoint directory while a system assuring updating is recommended. TRANSPARENCY: Assured by public access to annual ethics reports. The ethics reports bridged to the annual work plans (AWPs). EVALUATION: The Ethics Check by the Commission was successful.

HBM4EU feasibility studies: Lessons learned in combining health and human biomonitoring studies.

BACKGROUND: The European Human Biomonitoring Initiative (HBM4EU) is a joint program evaluating humans' exposure to several environmental substances and their potential health effects. One of the main objectives of HBM4EU is to make use of human biomonitoring (HBM) to assess human exposure to chemicals in Europe to better understand the associated health impacts and to improve chemical risk assessment. In parallel to HBM studies, health examination surveys (HESs), nutrition/dietary surveys, and disease specific health surveys are conducted in many European countries. In HESs, information collected by questionnaire(s) is supplemented with physical examinations and analysis of clinical and biological biomarkers in biological samples. HBM and health examination survey (HES) use similar data collection methods and infrastructures hence the feasibility of combining these two is explored in this paper. METHODS: Within HBM4EU, three feasibility studies (in Finland, Germany, and UK/England) were conducted to evaluate opportunities and obstacles of combining HBM and health studies. In this paper we report lessons learned from these feasibility studies. RESULTS: The Finnish feasibility study called KouBio-KUOPIO study was a new initiative without links to existing studies. The German feasibility study added a HBM module to the first follow-up examination of the LIFE-Adult-Study, a population-based cohort study. The UK feasibility integrates a sustainable HBM module into the Health Survey for England (HSfE), an annual health examination survey. Benefits of combining HBM and HESs include the use of shared infrastructures. Furthermore, participants can receive additional health information from HES, and participation rates tend to be higher due to the potential to obtain personal health information. Preparatory phases including obtaining ethical approval can be time-consuming and complicated. Recruitment of participants and low participation rates are common concerns in survey research and therefore designing user-friendly questionnaires with low participant burden is important. Unexpected events such as the COVID-19 pandemic can cause substantial challenges and delays for such studies. Furthermore, experiences from several countries demonstrated that long-term funding for combined studies can be difficult to obtain. CONCLUSIONS: In the future, incorporating HBM modules into existing HESs can provide a feasible and cost-effective method to conduct HBM studies and obtain a wide range of relevant data to support public health policies and research.

Effects of rifampicin on porphyrin metabolism in healthy volunteers.

Pregnane X receptor (PXR) is known to stimulate haem synthesis, but detailed knowledge on the effects of PXR activation on porphyrin metabolism in humans is lacking. We utilized a randomized, crossover, open (blinded laboratory) and placebo-controlled trial with 600-mg rifampicin or placebo dosed for a week to investigate the effects of PXR activation on erythrocyte, plasma, faecal and urine porphyrins. Sixteen healthy volunteers participated on the trial, but the number of volunteers for blood and urine porphyrin analyses was 15 while the number of samples for faecal analyses was 14. Rifampicin increased urine pentaporphyrin concentration 3.7-fold (mean 1.80 ± 0.6 vs. 6.73 ± 4.4 nmol/L, p = 0.003) in comparison with placebo. Urine coproporphyrin I increased 23% (p = 0.036). Faecal protoporphyrin IX decreased (mean 31.6 ± 23.5 vs. 19.2 ± 27.8 nmol/g, p = 0.023). The number of blood erythrocytes was slightly elevated, and plasma bilirubin, catabolic metabolite of haem, was decreased. In conclusion, rifampicin dosing elevated the excretion of certain urinary porphyrin metabolites and decreased faecal protoporphyrin IX excretion. As urine pentaporphyrin and coproporphyrin I are not precursors in haem biosynthesis, increased excretion may serve as a hepatoprotective shunt when haem synthesis or porphyrin levels are increased.

Development of non-communicable disease risk factors in Finland: projections up to 2040.

BACKGROUND: Non-communicable diseases are a major cause of mortality and morbidity worldwide. They share the same behavioural risk factors (smoking, sedentary behaviour, alcohol consumption and an unhealthy diet), all of which are modifiable risk factors, and biological consequences (hypertension, elevated total cholesterol, obesity and diabetes). METHODS: Using data from a series of cross-sectional health examination surveys conducted among the adult population in Finland from 1997 to 2017, a projection of risk factor development (smoking, leisure time sedentary behaviour, hypertension, elevated total cholesterol, overweight and obesity, and diabetes) up to the year 2040 was made. The projections were estimated using a multiple imputation method. RESULTS: Smoking prevalence is estimated to continue to decline up to 2040, similar to hypertension and elevated total cholesterol. By contrast, obesity and diabetes will develop unfavourably, with an increase in prevalence. The increase in obesity is mainly due to polarisation - that is, normal-weight people remain of a normal weight, but overweight people tend to gain more weight and become obese. The observed and estimated changes for leisure time sedentary lifestyle were not statistically significant. CONCLUSIONS: Projections of risk factors for non-communicable diseases are needed to guide public health policies and programmes, decision-making and the allocation of health care resources for prevention and care. In Finland, favourable developments have been seen in many of the risk factors, but obesity and diabetes show unfavourable development. There is a need to continue regular, systematic monitoring of the development of risk factors through health examination surveys and to set national goals and programmes to tackle the existing problems.