Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

The population history of northeastern Siberia since the Pleistocene

FGW – Publications without University Leiden contractDescriptive and Comparative Linguistic

The role of the fibrinolytic system in arterial and venous thrombosis

In this thesis, we investigated the role of the fibrinolytic system in arterial and venous thrombosis. The fibrinolytic system is responsible for the dissolution of a blood clot and involves multiple proteins for activation and regulation. The primary activators of fibrinolysis are plasminogen and tissue type plasminogen activator. The primary inhibitors are plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and alpha2-antiplasmin. Besides their function in clot dissolution, these proteins have functions in other processes, for example inflammation and insulin resistance. We measured levels of these five fibrinolytic factors in two case-control studies [Study of Myocardial Infarctions LEiden (SMILE) and Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study] to investigate their association with myocardial infarction and venous thrombosis. We also measured fibrinolytic potential in plasma with an overall assay, measuring the time necessary to dissolve a blood clot, i.e. clot lysis time (CLT). We hypothesized that increased CLT, increased levels of inhibitors, and decreased levels of activators of fibrinolysis were associated with increased risk of myocardial infarction and venous thrombosis and that CLT in the general population was determined by the combination of plasma levels of the different fibrinolytic factors. Prolonged CLT increased the risk of a first myocardial infarction, but only in men below 50 years of age, and of a first venous thrombosis. Not all fibrinolytic factors were associated with thrombosis-risk. Elevated TAFI levels were associated with a decreased and elevated alpha2-antiplasmin levels with an increased risk of myocardial infarction. Elevated PAI-1 and TAFI levels were associated with an increased risk of venous thrombosis. PAI-1 levels were the main determinants of CLT. Plasminogen, alpha2-antiplasmin, TAFI and prothrombin levels were also associated with CLT. Our results clearly indicate a difference between the role of the fibrinolytic system in myocardial infarction and its role in venous thrombosis and emphasize the difference in etiology of the diseases. An explanation for the difference in results between venous and arterial thrombosis may be that the primary function of the fibrinolytic proteins in venous thrombosis is fibrin clot dissolution, while in arterial thrombosis other roles of fibrinolytic proteins, such as in inflammation, plaque stabilization, and insulin resistance appear more important. We also studied CLT and TAFI in relation to a recurrent venous thrombotic event. CLT and TAFI levels did not constitute risk factors for recurrent venous thrombosis. Last, we showed increased CLT to be a risk factor for a first venous thrombosis in a large kindred exhibiting type I protein C deficiency and identified regions on chromosome 11 and 13 that may point to genetic variation influencing CLT. In conclusion, prolonged CLT, as measured with an overall plasma based assay, is associated with an increased risk of myocardial infarction and first venous thrombosis. The role of the individual fibrinolytic proteins in arterial and venous thrombosis is, however, less clear possibly in part due to pleiotropic effects of these factors. Nevertheless, we have provided evidence for a role of TAFI and PAI-1 in venous thrombosis, and for TAFI and alpha2-antiplasmin in arterial diseas

The Effect of Social Mixing Controls on the Spread of Smallpox - A Two-Level Model

Health Care Management Science, V. 8, No. 4, pp 277-289.Responding to a possible bioterror attack of Smallpox has become a major concern to governments, local public officials and health authorites. This concern has been reflected in numerous studies that model and evaluate possible response strategies. Many of these studies consider only vaccination policies and assume homogeneous mixing, where all instances of contacts in the population are equally like;y. Such a mixing pattern is rather unlikely to represent population interaction in a modern urban setting, which typically is separated into households on the one hand, and into daily meeting sites such as schools and offices on the other hand. In this paper we develop a two-level social interaction model where an individual moves back and forth between home and a daily meeting site, possibly passing through a general meeting site such as mass transit systems or other crowded areas. Based on the model, we evaluate the effect of social mixing controls, situational awareness of the public health system and mass vaccination on the spread of smallpox. It is shown that mixing controls and alertness of the response system may have a significant impact on the spread of the epidemic. Some policy recommendations are discussed