Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

Ambient air pollution exposure estimation for the global burden of disease 2013

Exposure to ambient air pollution is a major risk factor for global disease. Assessment of the impacts of air pollution on population health and the evaluation of trends relative to other major risk factors requires regularly updated, accurate, spatially resolved exposure estimates. We combined satellite-based estimates, chemical transport model (CTM) simulations and ground measurements from 79 different countries to produce new global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0.1° spatial resolution for five-year intervals from 1990-2010 and the year 2013. These estimates were then applied to assess population-weighted mean concentrations for 1990 – 2013 for each of 188 countries. In 2013, 87% of the world’s population lived in areas exceeding the World Health Organization (WHO) Air Quality Guideline of 10 μg/m3 PM2.5 (annual average). Between 1990 and 2013, decreases in population-weighted mean concentrations of PM2.5 were evident in most high income countries, in contrast to increases estimated in South Asia, throughout much of Southeast Asia, and in China. Population-weighted mean concentrations of ozone increased in most countries from 1990 - 2013, with modest decreases in North America, parts of Europe, and several countries in Southeast Asia.

The high burden of injuries in South Africa

Objective To estimate the magnitude and characteristics of the injury burden in South Africa within a global context. Methods The Actuarial Society of South Africa demographic and AIDS model (ASSA 2002) – calibrated to survey, census and adjusted vital registration data – was used to calculate the total number of deaths in 2000. Causes of death were determined from the National Injury Mortality Surveillance System profile. Injury death rates and years of life lost (YLL) were estimated using the Global Burden of Disease methodology. National years lived with disability (YLDs) were calculated by applying a ratio between YLLs and YLDs found in a local injury data source, the Cape Metropole Study. Mortality and disability-adjusted life years’ (DALYs) rates were compared with African and global estimates. Findings Interpersonal violence dominated the South African injury profile with age-standardized mortality rates at seven times the global rate. Injuries were the second-leading cause of loss of healthy life, accounting for 14.3% of all DALYs in South Africa in 2000. Road traffic injuries (RTIs) are the leading cause of injury in most regions of the world but South Africa has exceedingly high numbers – double the global rate. Conclusion Injuries are an important public health issue in South Africa. Social and economic determinants of violence, many a legacy of apartheid policies, must be addressed to reduce inequalities in society and build community cohesion. Multisectoral interventions to reduce traffic injuries are also needed. We highlight this heavy burden to stress the need for effective prevention programmes.

The first global entertainment company : explaining Pathe's dominance in the pre-Hollywood film industry

For almost a decade before Hollywood existed, French firm Pathe towered over the early film industry with estimates of its share of all films sold around the world varying between 50-70%. Pathe was the first global entertainment company. This paper analyses its rise to market leadership by applying a theoretical framework drawn from the business literature on causes of industry dominance, which provides insights into how firms acquire and maintain market dominance and in this case the film industry. This paper uses evidence presented by film historians to argue that Pathe "fits" the expected theoretical model of a dominant firm because it had a marketing orientation, used an effective quality-based competitive strategy and possessed the six critical marketing capabilities that business research shows enable the best performing firms to consistently outperform rivals.

Assessing the relationship between global warming and mortality : lag effects of temperature fluctuations by age and mortality categories

Although interests in assessing the relationship between temperature and mortality have arisen due to climate change, relatively few data are available on lag structure of temperature-mortality relationship, particularly in the Southern Hemisphere. This study identified the lag effects of mean temperature on mortality among age groups and death categories using polynomial distributed lag models in Brisbane, Australia, a subtropical city, 1996-2004. For a 1 °C increase above the threshold, the highest percent increase in mortality on the current day occurred among people over 85 years (7.2% (95% CI: 4.3%, 10.2%)). The effect estimates among cardiovascular deaths were higher than those among all-cause mortality. For a 1 °C decrease below the threshold, the percent increases in mortality at 21 lag days were 3.9% (95% CI: 1.9%, 6.0%) and 3.4% (95% CI: 0.9%, 6.0%) for people aged over 85 years and with cardiovascular diseases, respectively. These findings may have implications for developing intervention strategies to reduce and prevent temperature-related mortality.

The contribution of maize cropping in the Midwest USA to global warming: A regional estimate

Agricultural soils emit about 50% of the global flux of N2O attributable to human influence, mostly in response to nitrogen fertilizer use. Recent evidence that the relationship between N2O fluxes and N-fertilizer additions to cereal maize are non-linear provides an opportunity to estimate regional N2O fluxes based on estimates of N application rates rather than as a simple percentage of N inputs as used by the Intergovernmental Panel on Climate Change (IPCC). We combined a simple empirical model of N2O production with the SOCRATES soil carbon dynamics model to estimate N2O and other sources of Global Warming Potential (GWP) from cereal maize across 19,000 cropland polygons in the North Central Region (NCR) of the US over the period 1964–2005. Results indicate that the loading of greenhouse gases to the atmosphere from cereal maize production in the NCR was 1.7 Gt CO2e, with an average 268 t CO2e produced per tonne of grain. From 1970 until 2005, GHG emissions per unit product declined on average by 2.8 t CO2e ha−1 annum−1, coinciding with a stabilisation in N application rate and consistent increases in grain yield from the mid-1970’s. Nitrous oxide production from N fertilizer inputs represented 59% of these emissions, soil C decline (0–30 cm) represented 11% of total emissions, with the remaining 30% (517 Mt) from the combustion of fuel associated with farm operations. Of the 126 Mt of N fertilizer applied to cereal maize from 1964 to 2005, we estimate that 2.2 Mt N was emitted as N2O when using a non-linear response model, equivalent to 1.75% of the applied N.

The first global entertainment company : explaining Pathe's global dominance in the pre-Hollywood film industry

For almost a decade before Hollywood existed, French firm Pathe towered over the early film industry with estimates of its share of all films sold around the world varying between 50-70%. Pathe was the first global entertainment company. This paper analyses its rise to market leadership by applying a theoretical framework drawn from the business literature on causes of industry dominance, which provides insights into how firms acquire and maintain market dominance, and in this case the film industry. This paper uses evidence presented by film historians to argue that Pathe “fits” the expected theoretical model of a dominant firm because it had a marketing orientation, used an effective quality-based competitive strategy and possessed the six critical strategic marketing capabilities that business research shows enable the best performing firms to consistently outperform rivals

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Explaining Pathe's global dominance in the pre-Hollywood film industry

For almost a decade before Hollywood existed, French firm Pathe towered over the early film industry with estimates of its share of all films sold around the world varying between 50-70%. This paper analyses Pathe’s rise to market leadership by applying a theoretical framework drawn from the business literature on causes of industry dominance, that provides insights into how firms acquire and maintain market dominance. This paper uses evidence presented by film historians to argue that Pathe “fits” the expected theoretical model of the dominant firm because it had a marketing orientation, used an effective quality- based competitive strategy and possessed the six critical strategic marketing capabilities that business research shows enable the best performing firms to consistently outperform rivals.

The health effects of temperature : current estimates, future projections, and adaptation strategies

Climate change is expected to be one of the biggest global health threats in the 21st century. In response to changes in climate and associated extreme events, public health adaptation has become imperative. This thesis examined several key issues in this emerging research field. The thesis aimed to identify the climate-health (particularly temperature-health) relationships, then develop quantitative models that can be used to project future health impacts of climate change, and therefore help formulate adaptation strategies for dealing with climate-related health risks and reducing vulnerability. The research questions addressed by this thesis were: (1) What are the barriers to public health adaptation to climate change? What are the research priorities in this emerging field? (2) What models and frameworks can be used to project future temperature-related mortality under different climate change scenarios? (3) What is the actual burden of temperature-related mortality? What are the impacts of climate change on future burden of disease? and (4) Can we develop public health adaptation strategies to manage the health effects of temperature in response to climate change? Using a literature review, I discussed how public health organisations should implement and manage the process of planned adaptation. This review showed that public health adaptation can operate at two levels: building adaptive capacity and implementing adaptation actions. However, there are constraints and barriers to adaptation arising from uncertainty, cost, technologic limits, institutional arrangements, deficits of social capital, and individual perception of risks. The opportunities for planning and implementing public health adaptation are reliant on effective strategies to overcome likely barriers. I proposed that high priorities should be given to multidisciplinary research on the assessment of potential health effects of climate change, projections of future health impacts under different climate and socio-economic scenarios, identification of health cobenefits of climate change policies, and evaluation of cost-effective public health adaptation options. Heat-related mortality is the most direct and highly-significant potential climate change impact on human health. I thus conducted a systematic review of research and methods for projecting future heat-related mortality under different climate change scenarios. The review showed that climate change is likely to result in a substantial increase in heatrelated mortality. Projecting heat-related mortality requires understanding of historical temperature-mortality relationships, and consideration of future changes in climate, population and acclimatisation. Further research is needed to provide a stronger theoretical framework for mortality projections, including a better understanding of socioeconomic development, adaptation strategies, land-use patterns, air pollution and mortality displacement. Most previous studies were designed to examine temperature-related excess deaths or mortality risks. However, if most temperature-related deaths occur in the very elderly who had only a short life expectancy, then the burden of temperature on mortality would have less public health importance. To guide policy decisions and resource allocation, it is desirable to know the actual burden of temperature-related mortality. To achieve this, I used years of life lost to provide a new measure of health effects of temperature. I conducted a time-series analysis to estimate years of life lost associated with changes in season and temperature in Brisbane, Australia. I also projected the future temperaturerelated years of life lost attributable to climate change. This study showed that the association between temperature and years of life lost was U-shaped, with increased years of life lost on cold and hot days. The temperature-related years of life lost will worsen greatly if future climate change goes beyond a 2 °C increase and without any adaptation to higher temperatures. The excess mortality during prolonged extreme temperatures is often greater than the predicted using smoothed temperature-mortality association. This is because sustained period of extreme temperatures produce an extra effect beyond that predicted by daily temperatures. To better estimate the burden of extreme temperatures, I estimated their effects on years of life lost due to cardiovascular disease using data from Brisbane, Australia. The results showed that the association between daily mean temperature and years of life lost due to cardiovascular disease was U-shaped, with the lowest years of life lost at 24 °C (the 75th percentile of daily mean temperature in Brisbane), rising progressively as temperatures become hotter or colder. There were significant added effects of heat waves, but no added effects of cold spells. Finally, public health adaptation to hot weather is necessary and pressing. I discussed how to manage the health effects of temperature, especially with the context of climate change. Strategies to minimise the health effects of high temperatures and climate change can fall into two categories: reducing the heat exposure and managing the health effects of high temperatures. However, policy decisions need information on specific adaptations, together with their expected costs and benefits. Therefore, more research is needed to evaluate cost-effective adaptation options. In summary, this thesis adds to the large body of literature on the impacts of temperature and climate change on human health. It improves our understanding of the temperaturehealth relationship, and how this relationship will change as temperatures increase. Although the research is limited to one city, which restricts the generalisability of the findings, the methods and approaches developed in this thesis will be useful to other researchers studying temperature-health relationships and climate change impacts. The results may be helpful for decision-makers who develop public health adaptation strategies to minimise the health effects of extreme temperatures and climate change.

A simple model for the establishment of tick-borne pathogens of Ixodes scapularis : a global sensitivity analysis of R0

The basic reproduction number of a pathogen, R 0, determines whether a pathogen will spread (R0>1R 0>1), when introduced into a fully susceptible population or fade out (R0<1R 0<1), because infected hosts do not, on average, replace themselves. In this paper we develop a simple mechanistic model for the basic reproduction number for a group of tick-borne pathogens that wholly, or almost wholly, depend on horizontal transmission to and from vertebrate hosts. This group includes the causative agent of Lyme disease, Borrelia burgdorferi, and the causative agent of human babesiosis, Babesia microti, for which transmission between co-feeding ticks and vertical transmission from adult female ticks are both negligible. The model has only 19 parameters, all of which have a clear biological interpretation and can be estimated from laboratory or field data. The model takes into account the transmission efficiency from the vertebrate host as a function of the days since infection, in part because of the potential for this dynamic to interact with tick phenology, which is also included in the model. This sets the model apart from previous, similar models for R0 for tick-borne pathogens. We then define parameter ranges for the 19 parameters using estimates from the literature, as well as laboratory and field data, and perform a global sensitivity analysis of the model. This enables us to rank the importance of the parameters in terms of their contribution to the observed variation in R0. We conclude that the transmission efficiency from the vertebrate host to Ixodes scapularis ticks, the survival rate of Ixodes scapularis from fed larva to feeding nymph, and the fraction of nymphs finding a competent host, are the most influential factors for R0. This contrasts with other vector borne pathogens where it is usually the abundance of the vector or host, or the vector-to-host ratio, that determine conditions for emergence. These results are a step towards a better understanding of the geographical expansion of currently emerging horizontally transmitted tick-borne pathogens such as Babesia microti, as well as providing a firmer scientific basis for targeted use of acaricide or the application of wildlife vaccines that are currently in development.

The regional distribution of anxiety disorders : implications for the Global Burden of Disease Study, 2010

Anxiety disorders are increasingly acknowledged as a global health issue however an accurate picture of prevalence across populations is lacking. Empirical data are incomplete and inconsistent so alternate means of estimating prevalence are required to inform estimates for the new Global Burden of Disease Study 2010. We used a Bayesian meta-regression approach which included empirical epidemiological data, expert prior information, study covariates and population characteristics. Reported are global and regional point prevalence for anxiety disorders in 2010. Point prevalence of anxiety disorders differed by up to three-fold across world regions, ranging between 2.1% (1.8-2.5%) in East Asia and 6.1% (5.1-7.4%) in North Africa/Middle East. Anxiety was more common in Latin America; high income regions; and regions with a history of recent conflict. There was considerable uncertainty around estimates, particularly for regions where no data were available. Future research is required to examine whether variations in regional distributions of anxiety disorders are substantive differences or an artefact of cultural or methodological differences. This is a particular imperative where anxiety is consistently reported to be less common, and where it appears to be elevated, but uncertainty prevents the reporting of conclusive estimates.

The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study

Aim Estimate the prevalence of cannabis dependence and its contribution to the global burden of disease. Methods Systematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated. Results There were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally. Conclusion Cannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.

The epidemiological modelling of major depressive disorder : application for the global burden of disease study 2010

Background Although the detrimental impact of major depressive disorder (MDD) at the individual level has been described, its global epidemiology remains unclear given limitations in the data. Here we present the modelled epidemiological profile of MDD dealing with heterogeneity in the data, enforcing internal consistency between epidemiological parameters and making estimates for world regions with no empirical data. These estimates were used to quantify the burden of MDD for the Global Burden of Disease Study 2010 (GBD 2010). Method Analyses drew on data from our existing literature review of the epidemiology of MDD. DisMod-MR, the latest version of the generic disease modelling system redesigned as a Bayesian meta-regression tool, derived prevalence by age, year and sex for 21 regions. Prior epidemiological knowledge, study- and country-level covariates adjusted sub-optimal raw data. Results There were over 298 million cases of MDD globally at any point in time in 2010, with the highest proportion of cases occurring between 25 and 34 years. Global point prevalence was very similar across time (4.4% (95% uncertainty: 4.2–4.7%) in 1990, 4.4% (4.1–4.7%) in 2005 and 2010), but higher in females (5.5% (5.0–6.0%) compared to males (3.2% (3.0–3.6%) in 2010. Regions in conflict had higher prevalence than those with no conflict. The annual incidence of an episode of MDD followed a similar age and regional pattern to prevalence but was about one and a half times higher, consistent with an average duration of 37.7 weeks. Conclusion We were able to integrate available data, including those from high quality surveys and sub-optimal studies, into a model adjusting for known methodological sources of heterogeneity. We were also able to estimate the epidemiology of MDD in regions with no available data. This informed GBD 2010 and the public health field, with a clearer understanding of the global distribution of MDD.