| 1. |
- Hay, S. I., et al.
(författare)
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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
- 2017
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Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344
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Tidskriftsartikel (refereegranskat)abstract
- Background: 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 difered 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 ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve 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 ofset 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 eforts, and development assistance for health, including fnancial 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. © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 2. |
- Vos, T., et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
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Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 3. |
- Barber, R. M., et al.
(författare)
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Healthcare access and quality index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015 : A novel analysis from the global burden of disease study 2015
- 2017
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Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10091, s. 231-266
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Tidskriftsartikel (refereegranskat)abstract
- Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r=0·88), an index of 11 universal health coverage interventions (r=0·83), and human resources for health per 1000 (r=0·77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28·6 to 94·6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40·7 (95% uncertainty interval, 39·0-42·8) in 1990 to 53·7 (52·2-55·4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21·2 in 1990 to 20·1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73·8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-system characteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright © The Author(s). Published by Elsevier Ltd.
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| 4. |
- Shi, Liu, et al.
(författare)
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Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.
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| 5. |
- Shi, Liu, et al.
(författare)
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Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.
- 2019
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 15:11, s. 1478-1488
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Tidskriftsartikel (refereegranskat)abstract
- Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid.A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization.The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.
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| 6. |
- Shi, Liu, et al.
(författare)
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Replication study of plasma proteins relating to Alzheimer's pathology.
- 2021
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 17:9, s. 1452-1464
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Tidskriftsartikel (refereegranskat)abstract
- This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis.Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively.Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis.Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
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| 7. |
- Westwood, Sarah, et al.
(författare)
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Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer's Disease Multimodal Biomarker Discovery Cohort
- 2020
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 74:1, s. 213-225
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Tidskriftsartikel (refereegranskat)abstract
- We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.
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| 8. |
- Xu, Jin, et al.
(författare)
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Sex-Specific Metabolic Pathways Were Associated with Alzheimer's Disease (AD) Endophenotypes in the European Medical Information Framework for AD Multimodal Biomarker Discovery Cohort
- 2021
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: physiological differences between males and females could contribute to the development of Alzheimer's Disease (AD). Here, we examined metabolic pathways that may lead to precision medicine initiatives.METHODS: We explored whether sex modifies the association of 540 plasma metabolites with AD endophenotypes including diagnosis, cerebrospinal fluid (CSF) biomarkers, brain imaging, and cognition using regression analyses for 695 participants (377 females), followed by sex-specific pathway overrepresentation analyses, APOE ε4 stratification and assessment of metabolites' discriminatory performance in AD.RESULTS: In females with AD, vanillylmandelate (tyrosine pathway) was increased and tryptophan betaine (tryptophan pathway) was decreased. The inclusion of these two metabolites (area under curve (AUC) = 0.83, standard error (SE) = 0.029) to a baseline model (covariates + CSF biomarkers, AUC = 0.92, SE = 0.019) resulted in a significantly higher AUC of 0.96 (SE = 0.012). Kynurenate was decreased in males with AD (AUC = 0.679, SE = 0.046).CONCLUSIONS: metabolic sex-specific differences were reported, covering neurotransmission and inflammation pathways with AD endophenotypes. Two metabolites, in pathways related to dopamine and serotonin, were associated to females, paving the way to personalised treatment.
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