9 research outputs found
Hybrid quantum/classical docking of covalent and non-covalent ligands with Attracting Cavities
No full textLigand-protein docking aims to predict how a ligand binds to a biological macromolecule and is a fundamental technique in structure-based computer-aided drug design. However, accurately modeling covalent binding, metal coordination, and polarization effects remains challenging for classical docking algorithms. Here, we present an extension of our Attracting Cavities docking algorithm that enables hybrid quantum mechanical/molecular mechanical (QM/MM) calculations at various levels of theory. To evaluate its performance, we benchmarked the method on three diverse datasets covering non-covalent drug-target complexes, covalent complexes, and hemoprotein complexes, using both semi-empirical and density functional theory approaches. The results demonstrate that QM/MM docking is especially advantageous for metal-binding complexes, where the fast semi-empirical PM7 method yields a significant improvement over classical docking. When describing the active site residues at the density functional theory level, dispersion corrections are crucial for meaningful energies. Overall, the QM/MM method outperforms the classical approach for metalloproteins, performs comparably for covalent complexes, and shows slightly lower success rates for non-covalent complexes.
© 2025. The Author(s)
Automatic brain tumor segmentation in intra-operative ultrasound images using deep learning
No full textÅ få hjernesvulst er en alvorlig diagnose og kirurgisk fjerning av svulsten er den foretrukne behandlingsmåten. Pre-operativ magnetisk resonanstomografi (MRI) brukes som veiledning under operasjon. Men på grunn av vevsforskyvninger under operasjonen, så kan ikke MRI bildene stoles på fullt ut. Intraoperativ ultralydavbildning (US) kan brukes for å håntere dette ved å få et sanntidsbilde av svulstens plassering. Imidlertid, på grunn av variabel bildekvalitet og et begrenset synsfelt, så er disse bildene vanskelig å tolke. En automatisk segmentering av hjernesvulster i US-bilder kan derfor være et nyttig hjelpemiddel for nevrokirurger for å tolke bildene og lettere lokalisere svulstvev under operasjonen. Dyp læring kan brukes til å trene en slik model og tidligere studier konkluderer med at mer treningsdata er nødvendig for å forbedre resultatene. På grunn av dette ble det i dette prosjektet undersøkt om MRI-annoterte svulster kan brukes som en erstatning for US-annoterte svulster for å øke mengden treningsdata til en dyp lærlingsmodell for automatisk segmentering av hjernesvulster i intraoperative ultraldbilder.
For å studere dette ble annoterte pre-operative MRI-bilder og tilhørende intraoperative US-bilder tatt før påbegynt svulstfjerning, med og uten manuelle tumorannotasjoner, brukt. De MRI-annoterte svulstene ble samregistrert med de tilhørende US-bildene for å overføre svulstannotatsjonene til US-bildene som ikke har US-annotatsjoner. Deretter ble US-bildene med samregistrerte MRI-annoterte svulster og US-annoterte svulster brukt i forskjellige kombinasjoner, sammen og separat, for å trene en nnU-Net-modell for å studere modellene basert på de gitte treningsdataene. I tillegg ble 6 3D ultralydbilder manuellt annotert av forfatteren og validert av en erfaren nevrokirurg, og de ble sammenlignet med publiserte annotasjoner for å måle interobservasjonsvariabiliteten for å få et mål på hvor god modellen bør være.
Resultatene viste at å trene en dyp læringsmodell ved bruk av kun MRI-annoterte svulster oppnådde samme resultater som å trene med US-annoterte svulster. De beste resultatene ble oppnådd for en modell trent på begge typer annotasjoner. Denne modellen oppnådde en gjennomsnittlig Dice-score på 0,62. Dette er noe lavere enn den gjennomsnittlige Dice-scoren på 0,67, som ble målt for interobservasjonsvariabilitet på samme testsett. Imidlertid, for testbildene med et svulstareal større enn 200 mm^2, var modellen på nivå med nevrokirurgene, med en gjennomsnittlig Dice-score på 0,81 sammenlignet med 0,77 for interobservasjonsvariabilitet. I tillegg ble det observert en økning på nesten 43 % i den gjennomsnittlige Dice-scoren når kun bilder med et svulstsareal større enn 200 mm^2 ble brukt til trening, noe som tilsvarer kun 21 % av den tilgjengelige treningsdataen.
MRI-svulstannotasjoner kan dermed brukes som erstatning for US-svulstannotasjoner for å trene en automatisk hjernesvulstsegmenteringsmodell for intraoperative ultralydbilder. I tillegg er kvaliteten på treningsdataene viktig, ikke bare mengden treningsdata, og resultatene viste at det er mye å hente på å undersøke forskjellige konfigurasjoner av de tilgjengelige dataene for å optimalisere treningsdatasettet. Fremtidige studier bør også fokusere på å forbedre resultatene for bildene med små svulstareal og undersøke andre evalueringsmetrikker som ikke er følsomme for strukturstørrelser før klinisk implementering er mulig.For patients with the severe condition of having a malignant brain tumor, brain tumor resection surgery is the preferred treatment option. Pre-operative magnetic resonance imaging (MRI) images are used for guidance during surgery. Because of a phenomenon called brain shift, which is tissue displacement during surgery, the MRI images can not be fully trusted. To deal with this, intra-operative ultrasound imaging (US) can be used to get a real-time image of the location of the tumor. However, they are difficult to interpret due to variable image quality and limited field of view. An automatic segmentation of brain tumors in US images could thus be helpful for neurosurgeons to understand the images, and facilitate localization of tumor tissue during resection. Deep learning can be used to train such a model, and previous studies conclude that more data is needed to improve the result. Therefore, this project investigated whether MRI annotated tumors can be used as a substitute for US annotated tumors to enlarge the training set of a deep learning model for automatic brain tumor segmentation in intra-operative ultrasound images.
To study this, annotated pre-operative MRI images and corresponding intra-operative ultrasound images acquired before tumor resection, with and without manual tumor annotations, were used. The MRI annotated tumors were co-registered to the corresponding ultrasound images to transfer the tumor annotations to the ultrasound images without annotations. Next, the ultrasound images with the co-registered MRI annotated tumors and US annotated tumors were used in different combinations, together and separately, to train a nnU-Net model to study the performance based on the training data given. In addition, manual tumor annotations in the intra-operative ultrasound images were performed by the author and validated by an experienced neurosurgeon and compared to published annotations to measure the inter-observer variability to get a score of how good the model should be.
The results demonstrated that training a deep learning model using only MRI annotated tumors as labels achieved the same results as a model trained with US annotated tumors. Moreover, the best performance was found when the model was trained on both types of annotations. For this model, an average Dice score of 0.62 was obtained. This is slightly lower than the average Dice score of 0.67, which was measured for the inter-observer variability on the same dataset. However, for images with a tumor area larger than 200 mm^2, the model achieved results at the level of expert neurosurgeons with an average Dice score of 0.81 compared to 0.77 for the inter-observer variability. In addition, an increase of almost 43 % in the average Dice score was observed when only the images with a tumor area larger than 200 mm^2 were used for training, which corresponds to 21 % of the available training data.
MRI tumor annotation can thus indeed be used as US tumor labels to train an automatic brain tumor segmentation model for intra-operative ultrasound images. In addition, the quality of the training data is important, not just the quantity, and there is much to be gained by investigating different configurations of the available data to optimize the training dataset. Future studies should also focus on improving the results for images with small tumor areas and investigate other evaluation metrics that are not sensitive to structure sizes before a possible clinical implementation
Trehalose prevents aggregation of exosomes and cryodamage
No full textInternational audienceExosomes are important mediators in intercellular communication. Released by many cell types, they transport proteins, lipids, and nucleic acids to distant recipient cells and contribute to important physiopathological processes. Standard current exosome isolation methods based on differential centrifugation protocols tend to induce aggregation of particles in highly concentrated suspensions and freezing of exosomes can induce damage and inconsistent biological activity. Trehalose is a natural, non-toxic sugar widely used as a protein stabilizer and cryoprotectant by the food and drug industry. Here we report that addition of 25 mM trehalose to pancreatic beta-cell exosome-like vesicle isolation and storage buffer narrows the particle size distribution and increases the number of individual particles per microgram of protein. Repeated freeze-thaw cycles induce an increase in particle concentration and in the width of the size distribution for exosome-like vesicles stored in PBS, but not in PBS 25 mM trehalose. No signs of lysis or incomplete vesicles were observed by cryo-electron tomography in PBS and trehalose samples. In macrophage immune assays, beta-cell extracellular vesicles in trehalose show consistently higher TNF-alpha cytokine secretion stimulation indexes suggesting improved preservation of biological activity. The addition of trehalose might be an attractive means to standardize experiments in the field of exosome research and downstream applications. © The Author(s) 2016
Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants
No full textAbstractBackground: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher.Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.Findings: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7–128.3) in men and 122.3 mm Hg (121.0–123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9–79.5) for men and 76.7 mm Hg (75.9–77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4–27.1) in men and 20.1% (17.8–22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.Abstract
Background: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher.
Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.
Findings: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7–128.3) in men and 122.3 mm Hg (121.0–123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9–79.5) for men and 76.7 mm Hg (75.9–77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4–27.1) in men and 20.1% (17.8–22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.
Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe
Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants
No full textBACKGROUND: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher.METHODS: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.FINDINGS: We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7-128·3) in men and 122·3 mm Hg (121·0-123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9-79·5) for men and 76·7 mm Hg (75·9-77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4-27·1) in men and 20·1% (17·8-22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.INTERPRETATION: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.</p
Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants
No full textZhou B, Carrillo-Larco RM, Danaei G, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. LANCET. 2021;398(10304):957-980.Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
No full textThe last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles
Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
No full textBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
No full textBackground: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI).
Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate.
Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75.2 years (95% uncertainty interval 71.9-78.6) for females and 72.0 years (68.8-75.1) for males. The lowest for females was in the Central African Republic (45.6 years [42.0-49.5]) and for males was in Lesotho (41.5 years [39.0-44.0]). From 1990 to 2016, global HALE increased by an average of 6.24 years (5.97-6.48) for both sexes combined. Global HALE increased by 6.04 years (5.74-6.27) for males and 6.49 years (6.08-6.77) for females, whereas HALE at age 65 years increased by 1.78 years (1.61-1.93) for males and 1.96 years (1.69-2.13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2.3% [-5.9 to 0.9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16.1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally.
Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support
