Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Measurement of actual efficacy of compact fluorescent lamps (CFLs)

The use of compact fluorescent lamps (CFLs) in domestic residences has increased rapidly due to their higher energy efficiency and longer life expectancy when compared with traditional incandescent light bulbs. Through measurement of illuminance, actual power and apparent power, the actual efficacy and associated power factor of CFLs are studied in this paper. It is found that for an individual CFL, although its power consumption and lighting output (i.e. luminous flux) may be higher or lower than the stated values provided by the lighting manufacturers, the actual efficacy would most likely be equal to or better than the efficacy calculated from the given rated power and lumen from the manufacturers. The typical power factor for CFLs was 0.63.

Investment strategies in retirees' decumulation phase

This thesis consists of three studies on investment strategies for Australian retirees. Specifically, it investigates retirees' preference between alternative drawdown strategies in the presence of government pensions, appropriate management of longevity risk through the use of deferred annuities and asset allocation in retirement. It finds drawdown strategies linked to life expectancy to be the best performers. Deferred annuities are found to improve retirement incomes for risk averse retirees. For retirees who want to meet certain wealth thresholds in retirement, equity dominated portfolios provide superior outcomes for higher threshold levels.

Indoor air: Contemporary sources, exposures and global implications

Recent 'Global Burden of Disease' studies have provided quantitative evidence of the significant role air pollution plays as a human health risk factor (Lim et al., The Lancet, 380: 2224–2260, 2012). Tobacco smoke, including second hand smoke, household air pollution from solid fuels and ambient particulate matter are among the top risks, leading to lower life expectancy around the world. Indoor air constitutes an environment particularly rich in different types of pollutants, originating from indoor sources, as well as penetrating from outdoors, mixing, interacting or growing (when considering microbes) under the protective enclosure of the building envelope. Therefore, it is not a simple task to follow the dynamics of the processes occurring there, or to quantify the outcomes of the processes in terms of pollutant concentrations and other characteristics. This is further complicated by limitations such as building access for the purpose of air quality monitoring, or the instrumentation which can be used indoors, because of their possible interference with the occupants comfort (due to their large size, noise generated or amount of air drawn). European studies apportioned contributions of indoor versus outdoor sources of indoor air contaminants in 26 European countries and quantified IAQ associated DALYs (Disability-Adjusted Life Years) in those countries (Jantunen et al., Promoting actions for healthy indoor air (IAIAQ), European Commission Directorate General for Health and Consumers, Luxembourg, 2011). At the same time, there has been an increase in research efforts around the world to better understand the sources, composition, dynamics and impacts of indoor air pollution. Particular focus has been directed towards the contemporary sources, novel pollutants and new detection methods. The importance of exposure assessment and personal exposure, the majority of which occurs in various indoor micro¬environments, has also been realized. Overall, this emerging knowledge has been providing input for global assessments of indoor environments, the impact of indoor pollutants and their science based management and control. It was a major outcome of recent international conferences that interdisciplinarity and especially a better colla¬boration between exposure and indoor sciences would be of high benefit for the health related evaluation of environmental stress factors and pollutants. A very good example is the combination of biomonitoring and indoor air, particle and dust analysis to study the exposure routes of semi volatile organic compounds (SVOCs). We have adopted the idea of combining the forces of exposure and indoor sciences for this Special Issue, identified new and challenging topics and have attracted colleagues who are top researchers in their field to provide their inputs. The Special Issue includes papers, which collectively present advances in current research topics and in our view, build the bridge between indoor and exposure sciences.

4.2.5 Environmental engineering

Th is landmark report on engineering and development is the fi rst of its kind to be produced by UNESCO, or indeed by any international organization. Containing highly informative and insightful contributions from 120 experts from all over the world, the report gives a new perspective on the very great importance of the engineer’s role in development. Advances in engineering have been central to human progress ever since the invention of the wheel. In the past hundred and fi fty years in particular, engineering and technology have transformed the world we live in, contributing to signifi cantly longer life expectancy and enhanced quality of life for large numbers of the world’s population. Yet improved healthcare, housing, nutrition, transport, communications, and the many other benefi ts engineering brings are distributed unevenly throughout the world. Millions of people do not have clean drinking water and proper sanitation, they do not have access to a medical centre, they may travel many miles on foot along unmade tracks every day to get to work or school...

Super DNAging - New insights into DNA integrity, genome stability and telomeres in the oldest old

Reductions in DNA integrity, genome stability, and telomere length are strongly associated with the aging process, age-related diseases as well as the age-related loss of muscle mass. However, in people reaching an age far beyond their statistical life expectancy the prevalence of diseases, such as cancer, cardiovascular disease, diabetes or dementia, is much lower compared to “averagely” aged humans. These inverse observations in nonagenarians (90–99 years), centenarians (100–109 years) and super-centenarians (110 years and older) require a closer look into dynamics underlying DNA damage within the oldest old of our society. Available data indicate improved DNA repair and antioxidant defense mechanisms in “super old” humans, which are comparable with much younger cohorts. Partly as a result of these enhanced endogenous repair and protective mechanisms, the oldest old humans appear to cope better with risk factors for DNA damage over their lifetime compared to subjects whose lifespan coincides with the statistical life expectancy. This model is supported by study results demonstrating superior chromosomal stability, telomere dynamics and DNA integrity in “successful agers”. There is also compelling evidence suggesting that life-style related factors including regular physical activity, a well-balanced diet and minimized psycho-social stress can reduce DNA damage and improve chromosomal stability. The most conclusive picture that emerges from reviewing the literature is that reaching “super old” age appears to be primarily determined by hereditary/genetic factors, while a healthy lifestyle additionally contributes to achieving the individual maximum lifespan in humans. More research is required in this rapidly growing population of super old people. In particular, there is need for more comprehensive investigations including short- and long-term lifestyle interventions as well as investigations focusing on the mechanisms causing DNA damage, mutations, and telomere shortening.

Surgical fusion of early onset severe scoliosis increases survival in the child with rett syndrome: A population based study

Introduction. Rett Syndrome is a rare genetic neurodevelopmental disorder usually affecting females. Scoliosis is a common comorbidity and spinal fusion may be recommended if severe. Little is known about long term outcomes. We examined the impact of spinal fusion on survival and risk of severe lower respiratory tract infection (LRTI) in Rett Syndrome. Methods Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry of Rett Syndrome cases established in 1993, and the Australian Institute of Health and Welfare National Death Index database. An extended Cox regression model was used to estimate the effect of spinal surgery on survival in females who developed severe scoliosis (Cobb angle > 45 degrees). Generalized estimating equation modelling was used to estimate the effect of spinal surgery on the odds of developing severe LRTI. Results Severe scoliosis was identified in 140 cases (60.3%) of whom slightly fewer than half (48.6%) developed scoliosis prior to eight years of age. Scoliosis surgery was performed in 98 (69.0%) of those at a median age of 13 years 3 months (IQR 11 years 5 months – 14 years 10 months). After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (HR 0.30, 95% CI 0.12, 0.74, P = 0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06, 0.52, P = 0.002). Spinal fusion was not associated with reduction in the occurrence of a severe LRTI overall (OR 0.60, 95%CI 0.27, 1.33, P=0.206) but was associated with a large reduction in odds of severe LRTI among those with early onset scoliosis (OR 0.32, 95%CI 0.11, 0.93, P=0.036). Conclusion With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

Exploring aged care business models : A typological study

Australian providers of aged care are facing a rapidly ageing population and growth in demand for services. Beyond a sheer increase in consumers and major regulatory changes from Federal Government, many customers are becoming progressively discontented with a medically dominated model of care provision. This period of turbulence presents an opportunity for new entrants and forward-thinking organisations to disrupt the market by designing a more compelling value offering. Under this line of inquiry, the researchers conducted a qualitative content analysis study of over 37 Australian aged care organisations, clustering providers into six business model typologies. The study revealed that providers of aged care are becoming increasingly aware of emerging customer needs, and, in addressing these needs, are seeking to establish innovative models of care provision. This paper therefore presents a future model of care, along with implications for practice and policy.

Frailty: A key indicator to minimize inappropriate medication in older people

Older populations are more likely to have multiple co-morbid diseases that require multiple treatments, which make them a large consumer of medications. As a person grows older, their ability to tolerate medications becomes less due to age-related changes in pharmacokinetics and pharmacodynamics often heading along a path that leads to frailty. Frail older persons often have multiple co-morbidities with signs of impairment in activities of daily living. Prescribing drugs for these vulnerable individuals is difficult and is a potentially unsafe activity. Inappropriate prescribing in older population can be detected using explicit (criterion-based) or implicit (judgment-based) criteria. Unfortunately, most current therapeutic guidelines are applicable only to healthy older adults and cannot be generalized to frail patients. These discrepancies should be addressed either by developing new criteria or by refining the existing tools for frail older people. The first and foremost step is to identify the frail patient in clinical practice by applying clinically validated tools. Once the frail patient has been identified, there is a need for specific measures or criteria to assess appropriateness of therapy that consider such factors as quality of life, functional status and remaining life expectancy and thus modified goals of care.

Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: A cohort study

Aim Scoliosis is a common co-morbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Method Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. Results After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12–0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06–0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16–1.03; p=0.06). Interpretation With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

Dasatinib, nilotinib and standard-dose imatinib for the first line treatment of chronic myeloid leukaemia: Systematic reviews and economic analyses

- Background Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). - Objective This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML. - Data sources Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011. - Review methods A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis. - Results Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY. - Limitations Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions. - Conclusions From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML. - Funding The Health Technology Assessment Programme of the National Institute for Health Research.

Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

The experience of Indigenous students in a Bachelor of Nursing Program in Australia: cultural safety and decolonising nurse education

Background In Australia significant health inequalities, such as an 11year life expectancy gap, impact on the continent’s traditional owners, the Aboriginal peoples and Torres Strait Islanders. Evidence suggests links between improved Indigenous health and a greater proportion of Indigenous people employed in all sectors. Achieving a greater proportion of Indigenous people in health services and in the health education workforce, requires improved higher education completion rates. Currently Indigenous people are under-represented in higher education and attrition rates amongst those who do participate are high. We argue these circumstances make health and education matters of social justice, largely related to unexamined relations of power within universities where the pedagogical and social environment revolve around the norms and common-sense of the dominant culture. Project Research at Queensland University of Technology in 2010-2012, aimed to gain insights into attrition/retention in the Bachelor of Nursing. A literature review on Indigenous participation in higher education in nursing contextualised a mixed methods study. The project examined enrolment, attrition and success by an analysis of enrolment data from 1984-2012. Using Indigenous Research Assistants we then conducted 20 in-depth interviews with Indigenous students followed by a thematic analysis seeking to gain insights into the impact of students’ university experience on retention. Our findings indicate that cultural safety, mentorship, acceptance and support are crucial in student academic success. They also indicate that inflexible systems based on ethnocentric assumptions exacerbate the structural issues that impact on the students’ everyday life and are also part of the story of attrition. The findings reinforced the assumption that educational environments and processes are inherently cultural and political. This perspective calls into question the role of the students’ cultural experience at university in attrition rates. A partnership between the School of Nursing and the Indigenous Education Unit is working to better support Indigenous students.

Determination of the kallikrein-related peptidase 7 degradome and Transciptome in ovarian cancer

Ovarian cancer is the leading cause of cancer-related death in women, and the need for curative treatments is urgent. This study characterised an enzyme associated with the most lethal form of ovarian cancer, showing this enzyme to be a promising therapeutic target. Fifteen novel protein targets and key signalling pathways were determined to be regulated by this enzyme, kallikrein-related peptidase 7, in the ovarian tumour microenvironment, highlighting its involvement in cancer progression. Inhibition of this enzyme may be a useful therapeutic option to improve the life expectancy of women suffering from this cancer.

Healthy start: Closing the gap on Indigenous childhood obesity

We’ve recently seen some encouraging improvements in closing the gap on Indigenous disadvantage: better educational outcomes, higher child immunisation rates, more health checks, and a 35% drop in the gap between Indigenous and non-Indigenous child deaths. But Aboriginal and Torres Strait Islander people continue to suffer a much greater burden of ill-health than other Australians. The gap in Indigenous life expectancy at birth remains unacceptably high at 10.6 years for men and 9.5 years for women. Three-quarters of Indigenous deaths are from potentially avoidable causes. These include preventable conditions such as type 2 diabetes, cardiovascular disease and some cancers. A major contributor to these preventable conditions is excess body weight.