The compression of deaths above the mode

Kannisto (2001) has shown that as the frequency distribution of ages at death has shifted to the right, the age distribution of deaths above the modal age has become more compressed. In order to further investigate this old-age mortality compression, we adopt the simple logistic model with two parameters, which is known to fit data on old-age mortality well (Thatcher 1999). Based on the model, we show that three key measures of old-age mortality (the modal age of adult deaths, the life expectancy at the modal age, and the standard deviation of ages at death above the mode) can be estimated fairly accurately from death rates at only two suitably chosen high ages (70 and 90 in this study). The distribution of deaths above the modal age becomes compressed when the logits of death rates fall more at the lower age than at the higher age. Our analysis of mortality time series in six countries, using the logistic model, endorsed Kannisto’s conclusion. Some possible reasons for the compression are discussed.compression of mortality, lexis model, logistic model, modal age of death, oldest old mortality decline, standard deviation

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

Changes in (risk) behavior and HPV knowledge among Dutch girls eligible for HPV vaccination: an observational cohort study.

Implementation of human papillomavirus (HPV) vaccination raised concerns that vaccination could lead to riskier sexual behavior. This study explored how possible differences in sexual behavior and HPV knowledge developed over time between HPV-vaccinated and unvaccinated girls

Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness

Objective: To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening. Design: We used Portuguese national clinical and economic data to conduct a model-based assessment. Methods: We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness. Results: One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively. Conclusions: One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal’s challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings

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

Population health metrics: crucial inputs to the development of evidence for health policy

Valid, reliable and comparable measures of the health states of individuals and of the health status of populations are critical components of the evidence base for health policy. We need to develop population health measurement strategies that coherently address the relationships between epidemiological measures (such as risk exposures, incidence, and mortality rates) and multi-domain measures of population health status, while ensuring validity and cross-population comparability. Studies reporting on descriptive epidemiology of major diseases, injuries and risk factors, and on the measurement of health at the population level – either for monitoring trends in health levels or inequalities or for measuring broad outcomes of health systems and social interventions – are not well-represented in traditional epidemiology journals, which tend to concentrate on causal studies and on quasi-experimental design. In particular, key methodological issues relating to the clear conceptualisation of, and the validity and comparability of measures of population health are currently not addressed coherently by any discipline, and cross-disciplinary debate is fragmented and often conducted in mutually incomprehensible language or paradigms. Population health measurement potentially bridges a range of currently disjoint fields of inquiry relating to health: biology, demography, epidemiology, health economics, and broader social science disciplines relevant to assessment of health determinants, health state valuations and health inequalities. This new journal will focus on the importance of a population based approach to measurement as a way to characterize the complexity of people's health, the diseases and risks that affect it, its distribution, and its valuation, and will attempt to provide a forum for innovative work and debate that bridge the many fields of inquiry relevant to population health in order to contribute to the development of valid and comparable methods for the measurement of population health and its determinants