Harmonising summary measures of population health using global survey instruments.

measures of population health-health expectancies in particular-have become a standard for quantifying and monitoring population health. To date, cross-national comparability of health expectancies is limited, except within the European Union (EU). To advance international comparability, the European Joint Action on Healthy Life Years (JA: EHLEIS) set up an international working group. The working group discussed the conceptual basis of summary measures of population health and made suggestions for the development of comparable health expectancies to be used across the EU and Organisation for Economic Co-operation and Development (OECD) members. In this paper, which summarises the main results, we argue that harmonised health data needed for health expectancy calculation can best be obtained from 'global' survey measures, which provide a snapshot of the health situation using 1 or a few survey questions. We claim that 2 global measures of health should be pursued for their high policy relevance: a global measure of participation restriction and a global measure of functional limitation. We finally provide a blueprint for the future development and implementation of the 2 global measures. The blueprint sets the basis for subsequent international collaboration, having as a core group Member States of the EU, the USA and Japan. Other countries, in particular OECD members, are invited to join the initiative

Assessing the validity of the Global Activity Limitation Indicator in fourteen European countries.

BACKGROUND: The Global Activity Limitation Indicator (GALI), the measure underlying the European indicator Healthy Life Years (HLY), is widely used to compare population health across countries. However, the comparability of the item has been questioned. This study aims to further validate the GALI in the adult European population. METHODS: Data from the European Health Interview Survey (EHIS), covering 14 European countries and 152,787 individuals, were used to explore how the GALI was associated with other measures of disability and whether the GALI was consistent or reflected different disability situations in different countries. RESULTS: When considering each country separately or all combined, we found that the GALI was significantly associated with measures of activities of daily living, instrumental activity of daily living, and functional limitations (P < 0.001 in all cases). Associations were largest for activity of daily living and lowest though still high for functional limitations. For each measure, the magnitude of the association was similar across most countries. Overall, however, the GALI differed significantly between countries in terms of how it reflected each of the three disability measures (P < 0.001 in all cases). We suspect cross-country differences in the results may be due to variations in: the implementation of the EHIS, the perception of functioning and limitations, and the understanding of the GALI question. CONCLUSION: The study both confirms the relevance of this indicator to measure general activity limitations in the European population and the need for caution when comparing the level of the GALI from one country to another

Contribution of chronic diseases to the disability burden in a population 15 years and older, Belgium, 1997-2008.

BACKGROUND: Age-associated disability reduces quality of life in older populations and leads to wide-range implications for social and health policy. The identification of diseases that contribute to the disability burden is crucial to the development of prevention and intervention strategies to reduce disability. In this study, we assessed the contribution of chronic diseases to the prevalence of disability in Belgium. METHODS: Data from 35,837 individuals aged 15 years or older who participated in the 1997, 2001, 2004, or 2008 Belgian Health Interview Surveys were used. Disability was defined as difficulties in doing at least one of six activities of daily living (transfer in and out of bed, transfer in and out of chair, dressing, washing hands and face, feeding, and going to the toilet) and/or mobility limitations (ability to walk without stopping less than 200 m). Multiple additive regression models were fitted separately for men and women to estimate the age-specific background disability rate (experienced by everyone, independent of the presence of specific diseases) and disease-specific disability rates (disability rate in subjects who reported selected chronic diseases). RESULTS: Musculoskeletal, cardiovascular, and respiratory diseases were the main contributors to the disability burden in Belgium. Musculoskeletal diseases were the most prevalent diseases in men and women in all age groups. Neurological diseases and stroke were the most disabling diseases, i.e. caused the highest level of disability among the diseased individuals, in all age groups for men and women, respectively. Back pain was the main cause of disability in men aged 15 to 64 years, while heart attack was the major contributor to the disability prevalence in men aged 65 or older. Likewise, arthritis was the main cause of disability among women across all age groups. Depression was also an important contributor in young subjects (15-54 years). Cancer was not an important contributor to the disability prevalence in Belgium. CONCLUSIONS: To reduce the burden of disability in Belgium, interventions should target musculoskeletal, cardiovascular and respiratory diseases especially among elderly. Furthermore, attention should also be given to depression in young individuals

Contribution of chronic diseases to the disability burden in a population 15 years and older, Belgium, 1997-2008

Background: Age-associated disability reduces quality of life in older populations and leads to wide-range implications for social and health policy. The identification of diseases that contribute to the disability burden is crucial to the development of prevention and intervention strategies to reduce disability. In this study, we assessed the contribution of chronic diseases to the prevalence of disability in Belgium. Methods: Data from 35,837 individuals aged 15 years or older who participated in the 1997, 2001, 2004, or 2008 Belgian Health Interview Surveys were used. Disability was defined as difficulties in doing at least one of six activities of daily living (transfer in and out of bed, transfer in and out of chair, dressing, washing hands and face, feeding, and going to the toilet) and/or mobility limitations (ability to walk without stopping less than 200 m). Multiple additive regression models were fitted separately for men and women to estimate the age-specific background disability rate (experienced by everyone, independent of the presence of specific diseases) and disease-specific disability rates (disability rate in subjects who reported selected chronic diseases). Results: Musculoskeletal, cardiovascular, and respiratory diseases were the main contributors to the disability burden in Belgium. Musculoskeletal diseases were the most prevalent diseases in men and women in all age groups. Neurological diseases and stroke were the most disabling diseases, i.e. caused the highest level of disability among the diseased individuals, in all age groups for men and women, respectively. Back pain was the main cause of disability in men aged 15 to 64 years, while heart attack was the major contributor to the disability prevalence in men aged 65 or older. Likewise, arthritis was the main cause of disability among women across all age groups. Depression was also an important contributor in young subjects (15-54 years). Cancer was not an important contributor to the disability prevalence in Belgium. Conclusions: To reduce the burden of disability in Belgium, interventions should target musculoskeletal, cardiovascular and respiratory diseases especially among elderly. Furthermore, attention should also be given to depression in young individuals

The effect of smoking on the duration of life with and without disability, Belgium 1997-2011

Background: Smoking is the single most important health threat yet there is no consistency as to whether non-smokers experience a compression of years lived with disability compared to (ex-)smokers. The objectives of the manuscript are (1) to assess the effect of smoking on the average years lived without disability (Disability Free Life Expectancy (DFLE)) and with disability (Disability Life Expectancy (DLE)) and (2) to estimate the extent to which these effects are due to better survival or reduced disability in never smokers. Methods. Data on disability and mortality were provided by the Belgian Health Interview Survey 1997 and 2001 and a 10 years mortality follow-up of the survey participants. Disability was defined as difficulties in activities of daily living (ADL), in mobility, in continence or in sensory (vision, hearing) functions. Poisson and multinomial logistic regression models were fitted to estimate the probabilities of death and the prevalence of disability by age, gender and smoking status adjusted for socioeconomic position. The Sullivan method was used to estimate DFLE and DLE at age 30. The contribution of mortality and of disability to smoking related differences in DFLE and DLE was assessed using decomposition methods. Results: Compared to never smokers, ex-smokers have a shorter life expectancy (LE) and DFLE but the number of years lived with disability is somewhat larger. For both sexes, the higher disability prevalence is the main contributing factor to the difference in DFLE and DLE. Smokers have a shorter LE, DFLE and DLE compared to never smokers. Both higher mortality and higher disability prevalence contribute to the difference in DFLE, but mortality is more important among males. Although both male and female smokers experience higher disability prevalence, their higher mortality outweighs their disability disadvantage resulting in a shorter DLE. Conclusion: Smoking kills and shortens both life without and life with disability. Smoking related disability can however not be ignored, given its contribution to the excess years with disability especially in younger age groups

Assessing the validity of the global activity limitation indicator in fourteen European countries

Background: The Global Activity Limitation Indicator (GALI), the measure underlying the European indicator Healthy Life Years (HLY), is widely used to compare population health across countries. However, the comparability of the item has been questioned. This study aims to further validate the GALI in the adult European population. Methods: Data from the European Health Interview Survey (EHIS), covering 14 European countries and 152,787 individuals, were used to explore how the GALI was associated with other measures of disability and whether the GALI was consistent or reflected different disability situations in different countries. Results: When considering each country separately or all combined, we found that the GALI was significantly associated with measures of activities of daily living, instrumental activity of daily living, and functional limitations (P < 0.001 in all cases). Associations were largest for activity of daily living and lowest though still high for functional limitations. For each measure, the magnitude of the association was similar across most countries. Overall, however, the GALI differed significantly between countries in terms of how it reflected each of the three disability measures (P < 0.001 in all cases). We suspect cross-country differences in the results may be due to variations in: the implementation of the EHIS, the perception of functioning and limitations, and the understanding of the GALI question. Conclusion: The study both confirms the relevance of this indicator to measure general activity limitations in the European population and the need for caution when comparing the level of the GALI from one country to another

Anatomy of mouse recombination hot spots

Genome-wide analyses have suggested thousands of meiotic recombination hot spots across mammalian genomes. However, very few hot spots have been directly analyzed at a sub-kb scale for crossover (CO) activity. Using recombinant inbred strains as a CO library, here we report the identification and detailed characterization of seven new meiotic hot spots on mouse chromosome 19, more than doubling the number of currently available mouse hot spots. Although a shared feature is the narrow 1.5–2.5-kb width of these recombinogenic sites, these analyses revealed that hot spots have diverse sequence attributes and distinct symmetric and asymmetric CO profiles. Interestingly, CO molecules with discontinuous conversion tracts are commonly observed, contrasting with those found in human. Furthermore, unlike human hot spots, those present in the mouse do not necessarily have a quasi-normal CO distribution but harbor CO repulsion zones within recombinogenic cores. We propose a model where local chromatin landscape directs these repulsion zones

Genome-Wide Control of the Distribution of Meiotic Recombination

Meiotic recombination events are not randomly distributed in the genome but occur in specific regions called recombination hotspots. Hotspots are predicted to be preferred sites for the initiation of meiotic recombination and their positions and activities are regulated by yet-unknown controls. The activity of the Psmb9 hotspot on mouse Chromosome 17 (Chr 17) varies according to genetic background. It is active in strains carrying a recombinant Chr 17 where the proximal third is derived from Mus musculus molossinus. We have identified the genetic locus required for Psmb9 activity, named Dsbc1 for Double-strand break control 1, and mapped this locus within a 6.7-Mb region on Chr 17. Based on cytological analysis of meiotic DNA double-strand breaks (DSB) and crossovers (COs), we show that Dsbc1 influences DSB and CO, not only at Psmb9, but in several other regions of Chr 17. We further show that CO distribution is also influenced by Dsbc1 on Chrs 15 and 18. Finally, we provide direct molecular evidence for the regulation in trans mediated by Dsbc1, by showing that it controls the CO activity at the Hlx1 hotspot on Chr 1. We thus propose that Dsbc1 encodes for a trans-acting factor involved in the specification of initiation sites of meiotic recombination genome wide in mice

Identification of functional elements and regulatory circuits by Drosophila modENCODE

To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation