How to help countries improve resilience during a pandemic: an example of a Rapid Exchange Forum.

BACKGROUND: The COVID-19 pandemic demanded quick exchanges between experts and institutions supporting governments to provide evidence-based information in response to the crisis. Initially, there was no regular cross-country forum in the field of population health. This paper describes the set-up and benefits of implementing such a forum. METHODS: A group of public health practitioners from academia, national public health institutes and ministries of health decided in April 2020 to meet bi-monthly to discuss a vast array of population health topics in a structured format called a Rapid Exchange Forum (REF). An ad-hoc mailing group was established to collect responses to questions brought forward in the forum from at least five countries within 24 h. This endeavour, which evolved as network of networks was awarded an EU grant in autumn 2020 and was called PHIRI (Population Health Information Research Infrastructure). RESULTS: Responses from up to 31 countries were compiled and shared immediately via the European Health Information Portal. This exchange was complemented by special REFs that focused on the advantages and disadvantages of vaccination, for example. By July 2023, 54 REFs had taken place with topics going beyond COVID-19. CONCLUSION: The REF demonstrated its value for quick yet evidence-based cross-country exchange in times of crisis and was highly appreciated by countries and European Commission. It demonstrated its sustainability even after the acute crisis by expanding the topics covered and managing to continue exchange with the aim of capacity building and mutual learning, making it a true EU response and coordination mechanism.

COVID-19 health information system assessments in eight European countries: identified gaps, best practices and recommendations.

BACKGROUND: Global threats, such as the coronavirus disease 2019 (COVID-19) pandemic, have highlighted the critical importance of robust and well-functioning health information systems (HIS) in effectively addressing public health emergencies. To enhance the understanding and the functioning of such systems, it is crucial to perform HIS assessments. This article explores key gaps and identifies best practices in the COVID-19 HIS of eight European countries. Furthermore, it provides recommendations to strengthen European systems for better pandemic preparedness. METHODS: Assessments were carried out in eight European countries using an adapted version of the WHO support tool to strengthen HIS and the Joint Action on Health Information assessment tool. The assessments took place between January 2022 and April 2023. RESULTS: Four main themes emerged regarding the gaps and best practices identified in the various HIS: organizational, technical, legal and resources. The results of these assessments show different approaches implemented by countries to improve their HIS and respond to the demands of the pandemic. CONCLUSIONS: It is imperative for countries to draw valuable insights from the COVID-19 pandemic and strengthen their HIS. This involves the adaptation or development of pandemic preparedness plans, strengthening legislative framework for data sharing and privacy protection, promotion of data standards and international definitions and implementation of a unique person identifier. Additionally, countries will have to act in this post-pandemic era and integrate the newly developed systems and innovations into existing structures, maintain and develop trust by citizens through transparent communication and engage in infodemic management and address resource gaps in the workforce.

European Health Information Training Programme: a sustainable strategy for strengthening capacity in health information.

BACKGROUND: Before the COVID-19 pandemic, a need for a uniform approach to health information (HI) knowledge in population health analysis across Europe was evident. The Population Health Information Research Infrastructure (PHIRI) emerged as a proactive initiative to strengthen European HI capacities. This article describes the achievements of PHIRI, highlighting its capacity-building activities and their contribution towards a sustainable strategy for the implementation of the European Health Data Space (EHDS). METHODS: PHIRI collaboration established a work package for skill-building activities in population health in partnership with other organizations. Activities included webinars, workshops, sessions, training schools and courses for researchers and public administration workers from Europe and beyond. The primary goal of the activities was to examine the impact of COVID-19 on European health systems at both local and national levels, including healthcare facilities and policymaking entities. RESULTS: Twelve activities were organized between October 2020 and the summer of 2023. In March 2023, the Spring School on Health Information was organized to share the knowledge achieved from PHIRI and other European Union-related projects. This event also validated the European Health Information Training Programme. CONCLUSIONS: PHIRI's findings emphasized the importance of equipping the workforce with core HI skills to improve health systems' preparedness and resilience. Through this research, it is possible to propose a strategy for building capacity that emphasizes the importance of providing training in human-machine dynamics. This approach will contribute to the sustainable implementation of the EHDS.

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.

Delayed treatment in breast cancer patients during the COVID-19 pandemic: a population health information research infrastructure (PHIRI) case study.

BACKGROUND: The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021. METHODS: An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays. RESULTS: We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic's beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic's start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level. CONCLUSIONS: Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.

Heritability of objectively assessed and self-reported sedentary behavior.

Understanding the sources of the large individual differences in sedentary behavior is of great importance as this behavior is associated with pre-mature mortality and non-communicable diseases. Here, we report on the contribution of genetic and environmental factors to the variation in objectively assessed (accelerometer) sedentary behavior and self-reported sitting and their shared genetic basis. In addition, the overlap of the genetic risk factors influencing sedentary time and moderate-to-vigorous physical activity (MVPA) was estimated. A sample of 800 individuals (twins and their siblings) was equipped with an Actigraph accelerometer for 7 days and reported on their sitting time and time spent on MVPA on those days using the IPAQ-SF. Genetic factors explained 56% (CI: 44%, 65%) of the individual differences in objective sedentary behavior (Actigraph) and 26% (CI: 0%, 51%) of the individual differences in self-reported sedentary behavior (IPAQ-SF). A modest correlation (0.33) was found between these measures, which was for 45% accounted for by genetic influences. The genetic correlation was 0.49 reflecting a partly overlapping set of genes that influenced both measurements. A modest correlation (-0.27) between Actigraph-derived sedentary time and MVPA was found, which was 13% accounted for by genetic effects. The genetic correlation was -0.31, indicating that there are overlapping genetic variants that increase sedentary time and decrease MVPA or vice versa. To conclude, more than half of the individual differences in objective sedentary time could be attributed to genetic differences, while for self-reported sitting this was much lower. In addition, using objective measurements, this study confirms that sedentary time is not simply the inverse of MVPA. Future studies are needed to understand the pathways translating genomic variation into variation in these behaviors and how this knowledge might feed into the development of health promotion interventions.

Heritability of the affective response to exercise and its correlation to exercise behavior.

OBJECTIVES: Individual differences in adolescent exercise behavior are strongly influenced by genetic factors. The affective response to exercise is a potential source of these genetic influences. To test its role in the motivation to exercise, we estimated the heritability of the affective responses during and after exercise and the overlap with the genetic factors influencing regular voluntary exercise behavior. DESIGN: 226 twin pairs and 38 siblings completed two submaximal exercise tests on a cycle ergometer and a treadmill and a maximal exercise test on a cycle ergometer. Affective responses were assessed by the Feeling Scale (FS), Borg's Rating of Perceived Exertion (RPE) and the Activation-Deactivation Adjective Checklist (AD ACL). METHODS: Multivariate structural equation modeling was used to estimate heritability of the affective responses during and after submaximal and maximal exercise and the (genetic) correlation with self-reported regular voluntary exercise behavior over the past year. RESULTS: Genetic factors explained 15% of the individual differences in FS responses during the cycle ergometer test, as well as 29% and 35% of the individual differences in RPE during the cycle ergometer and treadmill tests, respectively. For the AD ACL scales, heritability estimates ranged from 17% to 37% after submaximal exercise and from 12% to 37% after maximal exercise. Without exception, more positive affective responses were associated with higher amounts of regular exercise activity (.15 < r < .21) and this association was accounted for by an overlap in genetic factors influencing affective responding and exercise behavior. CONCLUSIONS: We demonstrate low to moderate heritability estimates for the affective response during and after exercise and significant (genetic) associations with regular voluntary exercise behavior. These innate individual differences in the affective responses to exercise should be taken into account in interventions aiming to motivate adolescents to adopt and maintain regular exercise.

Twin-sibling study and meta-analysis on the heritability of maximal oxygen consumption.

Large individual differences exist in aerobic fitness in childhood and adolescence, but the relative contribution of genetic factors to this variation remains to be established. In a sample of adolescent twins and siblings (n = 479), heart rate (HR) and maximal oxygen uptake (V̇o2max) were recorded during the climax of a graded maximal exercise test. In addition, V̇o2max was predicted in two graded submaximal exercise tests on the cycle ergometer and the treadmill, using extrapolation of the HR/V̇o2 curve to the predicted HRmax. Heritability estimates for measured V̇o2max were 60% in ml/min and 55% for V̇o2max in ml·min(-1)·kg(-1). Phenotypic correlations between measured V̇o2max and predicted V̇o2max from either submaximal treadmill or cycle ergometer tests were modest (0.57 < r < 0.70), in part because of the poor agreement between predicted and actual HRmax. The majority of this correlation was explained by genetic factors; therefore, the submaximal exercise tests still led to very comparable estimates of heritability of V̇o2max. To arrive at a robust estimate for the heritability of V̇o2max in children to young adults, a sample size weighted meta-analysis was performed on all extant twin and sibling studies in this age range. Eight studies, including the current study, were meta-analyzed and resulted in a weighted heritability estimate of 59% (ml/min) and 72% (ml·min(-1)·kg(-1)) for V̇o2max. Taken together, the twin-sibling study and meta-analyses showed that from childhood to early adulthood genetic factors determine more than half of the individual differences in V̇o2max.

Differences in Adolescent Physical Fitness: A Multivariate Approach and Meta-analysis.

Physical fitness can be defined as a set of components that determine exercise ability and influence performance in sports. This study investigates the genetic and environmental influences on individual differences in explosive leg strength (vertical jump), handgrip strength, balance, and flexibility (sit-and-reach) in 227 healthy monozygotic and dizygotic twin pairs and 38 of their singleton siblings (mean age 17.2 ± 1.2). Heritability estimates were 49% (95% CI 35-60%) for vertical jump, 59% (95% CI 46-69%) for handgrip strength, 38% (95% CI 22-52%) for balance, and 77% (95% CI 69-83%) for flexibility. In addition, a meta-analysis was performed on all twin studies in children, adolescents and young adults reporting heritability estimates for these phenotypes. Fifteen studies, including results from our own study, were meta-analyzed by computing the weighted average heritability. This showed that genetic factors explained most of the variance in vertical jump (62%; 95% CI 47-77%, N = 874), handgrip strength (63%; 95% CI 47-73%, N = 4516) and flexibility (50%; 95% CI 38-61%, N = 1130) in children and young adults. For balance this was 35% (95% CI 19-51%, N = 978). Finally, multivariate modeling showed that the phenotypic correlations between the phenotypes in current study (0.07 < r < 0.27) were mostly driven by genetic factors. It is concluded that genetic factors contribute significantly to the variance in muscle strength, flexibility and balance; factors that may play a key role in the individual differences in adolescent exercise ability and sports performance.

Heritability of heart rate recovery and vagal rebound after exercise.

PURPOSE: The prognostic power of heart rate recovery (HRR) after exercise has been well established but the exact origin of individual differences in HRR remains unclear. This study aims to estimate the heritability of HRR and vagal rebound after maximal exercise in adolescents. Furthermore, the role of voluntary regular exercise behavior (EB) in HRR and vagal rebound is tested. METHODS: 491 healthy adolescent twins and their siblings were recruited for maximal exercise testing, followed by a standardized cooldown with measurement of the electrocardiogram and respiratory frequency. Immediate and long-term HRR (HRR60 and HRR180) and vagal rebound (heart rate variability in the respiratory frequency range) were assessed 1 and 3 min after exercise. Multivariate twin modeling was used to estimate heritability of all measured variables and to compute the genetic contribution to their covariance. RESULTS: Heritability of HRR60, HRR180 and immediate and long-term vagal rebound is 60 % (95 % CI: 48-67), 65 % (95 % CI: 54-73), 23 % (95 % CI: 11-35) and 3 % (95 % CI: 0-11), respectively. We find evidence for two separate genetic factors with one factor influencing overall cardiac vagal control, including resting heart rate and respiratory sinus arrhythmia, and a specific factor for cardiac vagal exercise recovery. EB was only modestly associated with resting heart rate (r = -0.27) and HRR (rHRR60 = 0.10; rHRR180 = 0.19) with very high genetic contribution to these associations (88-91 %). CONCLUSIONS: Individual differences in HRR and immediate vagal rebound can to a large extent be explained by genetic factors. These innate cardiac vagal exercise recovery factors partly reflect the effects of heritable differences in EB.

Heritability of resting state EEG functional connectivity patterns.

We examined the genetic architecture of functional brain connectivity measures in resting state electroencephalographic (EEG) recordings. Previous studies in Dutch twins have suggested that genetic factors are a main source of variance in functional brain connectivity derived from EEG recordings. In addition, qualitative descriptors of the brain network derived from graph analysis - network clustering and average path length - are also heritable traits. Here we replicated previous findings for connectivity, quantified by the synchronization likelihood, and the graph theoretical parameters cluster coefficient and path length in an Australian sample of 16-year-old twins (879) and their siblings (93). Modeling of monozygotic and dizygotic twins and sibling resemblance indicated heritability estimates of the synchronization likelihood (27-74%) and cluster coefficient and path length in the alpha and theta band (40-44% and 23-40% respectively) and path length in the beta band frequency (41%). This corroborates synchronization likelihood and its graph theoretical derivatives cluster coefficient and path length as potential endophenotypes for behavioral traits and neurological disorders.

The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children.

The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.

Innovative Methods Used in Monitoring COVID-19 in Europe: A Multinational Study.

Several innovative methods have been deployed worldwide to curb the COVID-19 pandemic. The aim of the study is to investigate which innovative methods are used to monitor COVID-19 health issues in Europe and related legislative and ethical aspects. An online questionnaire was administered to European countries' representatives of the project Population Health Information Research Infrastructure. Additional information was obtained from websites and documents provided by the respondents; an overview of the literature was also performed. Respondents from 14 countries participated in the study. Digital tools are used to monitor the spread of COVID-19 (13/14 countries) and vaccination coverage (12/14); for research, diagnostics, telehealth (14/14); to fight disinformation (11/14) and forecast the pandemic spread (4/14). The level of implementation of telehealth applications was mostly low/medium. Legislative and ethical issues were encountered in many countries, leading to institutional distrust. The COVID-19 pandemic has highlighted the need for timely and accurate health data for research purposes and policy planning. However, the use of innovative methods for population health monitoring and timely data collection has posed challenges to privacy and online security globally. Adequate regulatory oversight, targeted public health interventions, and fight against disinformation could improve the uptake rate and enhance countries' emergency preparedness.

Opportunities for a population-based cohort in Belgium.

Population-based cohorts allow providing answers to a wide range of policy-relevant research questions. In Belgium, existing cohort-like initiatives are limited by their focus on specific population groups or specific topics, or they lack a true longitudinal design. Since 2016, consultations and deliberative processes have been set up to explore the opportunities for a population-based cohort in Belgium. Through these processes, several recommendations emerged to pave the way forward - i.e., to facilitate the establishment of administrative linkages, increase digitalisation, secure long-term financial and organisational efforts, establish a consortium of the willing, and identify and tackle ethical and legal bottlenecks. This comment summarizes these recommendations, as these opportunities should be explored in depth to consolidate the existing collaborations between different stakeholders, and refers to current initiatives that can further facilitate the establishment of a Belgian population-based cohort and, more generally, administrative and health data linkage and reuse for research and policy-making.

Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents.

Background Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood. The main aim was to determine the maturation of different cardiac sympathetic-(SNS) and parasympathetic nervous system (PNS) activity parameters in healthy patients aged 0.5 to 20 years. A second aim was to determine potential sex differences. Methods and Results Five studies covering the 0.5- to 20-year age range provided impedance- and electrocardiography recordings from which heart rate, different PNS-parameters (eg, respiratory sinus arrhythmia) and an SNS-parameter (pre-ejection period) were collected. Age trends were computed in the mean values across 12 age-bins and in the age-specific variances. Age was associated with changes in mean and variance of all parameters. PNS-activity followed a cubic trend, with an exponential increase from infancy, a plateau phase during middle childhood, followed by a decrease to adolescence. SNS-activity showed a more linear trend, with a gradual decrease from infancy to adolescence. Boys had higher SNS-activity at ages 11 to 15 years, while PNS-activity was higher at 5 and 11 to 12 years with the plateau level reached earlier in girls. Interindividual variation was high at all ages. Variance was reasonably stable for SNS- and the log-transformed PNS-parameters. Conclusions Cardiac PNS- and SNS-activity in childhood follows different maturational trajectories. Whereas PNS-activity shows a cubic trend with a plateau phase during middle childhood, SNS-activity shows a linear decrease from 0.5 to 20 years. Despite the large samples used, clinical use of the sex-specific centile and percentile normative values is modest in view of the large individual differences, even within narrow age bands.

Estimated preejection period (PEP) based on the detection of the R-wave and dZ/dt-min peaks does not adequately reflect the actual PEP across a wide range of laboratory and ambulatory conditions.

The current study evaluates the validity of the PEP computed from a fixed value for the Q-wave onset to R-wave peak (QR) interval and an R-wave peak to B-point (RB) interval that is estimated from the R-peak to dZ/dt-min peak (ISTI) interval. Ninety-one subjects participated in a 90min laboratory experiment in which a variety of often employed physical and mental stressors were presented and 31 further subjects participated in a structured 2hour ambulatory recording in which they partook in natural activities that induced large variation in posture and physical activity. PEP, QR interval, and ISTI were scored and rigorously checked by interactive inspection. Across the very diverse laboratory and ambulatory conditions the QR interval could be approximated by a fixed interval of 40ms but 95% confidence intervals were large (25.5 to 54.5ms). Multilevel analysis showed that 79% to 81% of the within and between-subject variation in the RB interval could be predicted by the ISTI with a simple linear regression equation. However, the optimal intercept and slope values in this equation varied significantly across subjects and study setting. Bland Altman plots revealed a large discrepancy between the estimated PEP using the R-wave peak and dZ/dt-min peak and the actual PEP based on the Q-wave onset and B-point. We conclude that the PEP estimated from a fixed QR interval and the ISTI could be a useful addition to the psychophysiologist's toolbox, but that it cannot replace the actual PEP to index cardiac sympathetic control.