Gender differences in health of EU10 and EU15 populations: the double burden of EU10 men

This study compares gender differences in Healthy Life Years (HLY) and unhealthy life years (ULY) between the original (EU15) and new member states (EU10). Based on the number of deaths, population and prevalence of activity limitations from the Statistics of Living and Income Conditions Survey (SILC) survey, we calculated HLY and ULY for the EU10 and EU15 in 2006 with the Sullivan method. We used decomposition analysis to assess the contributions of mortality and disability and age to gender differences in HLY and ULY. HLY at age 15 for women in the EU10 were 3.1 years more than those for men at the same age, whereas HLY did not differ by gender in the EU15. In both populations ULY at age 15 for women exceeded those for men by 5.5 years. Decomposition showed that EU10 women had more HLY because higher disability in women only partially offset (−0.8 years) the effect of lower mortality (+3.9 years). In the EU15 women’s higher disability prevalence almost completely offset women’s lower mortality. The 5.3 fewer ULY in EU10 men than in EU10 women mainly reflected higher male mortality (4.5 years), while the fewer ULY in EU15 men than in EU15 women reflected both higher male mortality (2.9 years) and higher female disability (2.6 years). The absence of a clear gender gap in HLY in the EU15 thus masked important gender differences in mortality and disability. The similar size of the gender gap in ULY in the EU-10 and EU-15 masked the more unfavourable health situation of EU10 men, in particular the much stronger and younger mortality disadvantage in combination with the virtually absent disability advantage below age 65 in men

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

A randomized trial to optimize HIV/TB care in South Africa: design of the Sizanani trial

Background: Despite increases in HIV testing, only a fraction of people newly diagnosed with HIV infection enter the care system and initiate antiretroviral therapy (ART) in South Africa. We report on the design and initial enrollment of a randomized trial of a health system navigator intervention to improve linkage to HIV care and TB treatment completion in Durban, South Africa. Methods/Design We employed a multi-site randomized controlled trial design. Patients at 4 outpatient sites were enrolled prior to HIV testing. For all HIV-infected participants, routine TB screening with sputum for mycobacterial smear and culture were collected. HIV-infected participants were randomized to receive the health system navigator intervention or usual care. Participants in the navigator arm underwent a baseline interview using a strengths-based case management approach to assist in identifying barriers to entering care and devising solutions to best cope with perceived barriers. Over 4 months, participants in the navigator arm received scheduled phone and text messages. The primary outcome of the study is linkage and retention in care, assessed 9 months after enrollment. For ART-eligible participants without TB, the primary outcome is 3 months on ART as documented in the medical record; participants co-infected with TB are also eligible to meet the primary outcome of completion of 6 months of TB treatment, as documented by the TB clinic. Secondary outcomes include mortality, receipt of CD4 count and TB test results, and repeat CD4 counts for those not ART-eligible at baseline. We hypothesize that a health system navigator can help identify and positively affect modifiable patient factors, including self-efficacy and social support, that in turn can improve linkage to and retention in HIV and TB care. Discussion We are currently evaluating the clinical impact of a novel health system navigator intervention to promote entry to and retention in HIV and TB care for people newly diagnosed with HIV. The details of this study protocol will inform clinicians, investigators, and policy makers of strategies to best support HIV-infected patients in resource-limited settings. Trial registration Clinicaltrials.gov. unique identifier: NCT01188941

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants

This is the final version of the article. Available from the publisher via the DOI in this record.Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus(CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival. Less common variants requiring further confirmation were also identified. Offspring of longer lived parents had more protective alleles for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not. Associations between extreme longevity (mother >=98 years, fathers >=95 years, n=1,339) and disease alleles were similar, with an additional association with HDL cholesterol (p=5.7x10-3). These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable.This work was generously funded by an award to DM, TF, AM, LH and CB by the Medical Research Council MR/M023095/1. This research has been conducted using the UK Biobank Resource, under application 1417. The authors wish to thank the UK Biobank participants and coordinators for this unique dataset. S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1). J.T. is funded by a Diabetes Research and Wellness Foundation Fellowship. R.B. is funded by the Wellcome Trust and Royal Society grant: 104150/Z/14/Z. M.A.T., M.N.W. and A.M. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF). R.M.F. is a Sir Henry Dale Fellow (Wellcome Trust and Royal Society grant: 104150/Z/14/Z). A.R.W. H.Y., and T.M.F. are supported by the European Research Council grant: 323195:GLUCOSEGENES-FP7-IDEAS-ERC. The funders had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Framingham Heart Study is supported by Contract No. N01-HC-25195 and HHSN268201500001I and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). The phenotypegenotype association analyses were supported by National Institute of Aging R01AG29451. This work has made use of the resources provided by the University of Exeter Science Strategy and resulting Systems Biology initiative. Primarily these include high-performance computing facilities managed by Konrad Paszkiewicz of the College of Environmental and Life Sciences and Pete Leggett of the University of Exeter Academics services unit

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

Assessing heat-related health risk in Europe via the Universal Thermal Climate Index (UTCI)

In this work the potential of the Universal Thermal Climate Index (UTCI) as a heat-related health risk indicator in Europe is demonstrated. The UTCI is a bioclimate index that uses a multi-node human heat balance model to represent the heat stress induced by meteorological conditions to the human body. Using 38 years of meteorological reanalysis data, UTCI maps were computed to assess the thermal bioclimate of Europe for the summer season. Patterns of heat stress conditions and non-thermal stress regions are identified across Europe. An increase in heat stress up to 1°C is observed during recent decades. Correlation with mortality data from 17 European countries revealed that the relationship between the UTCI and death counts depends on the bioclimate of the country, and death counts increase in conditions of moderate and strong stress, i.e. when UTCI is above 26°C and 32°C. The UTCI’s ability to represent mortality patterns is demonstrated for the 2003 European heatwave. These findings confirm the importance of UTCI as a bioclimatic index that is able to both capture the thermal bioclimatic variability of Europe, and relate such variability with the effects it has on human health