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BACKGROUND: The aims of this study were to establish national disability weights based on the health state preferences of a Dutch general population sample, examine the relation between results and respondent's characteristics, and compare disability weights with those estimated in the European disability weights study. METHODS: In this cross-sectional study, a web-based survey was administered to a general population 18-75 years from the Netherlands. The survey included paired comparison questions. Paired comparison data were analysed using probit regression and located results onto the 0-to-1 disability weight scale using non-parametric regression. Bootstrapping was used to estimate 95% uncertainty intervals (95%UI). Spearman's correlation was used to investigate the relation of probit regression coefficients between respondent's characteristics. RESULTS: 3994 respondents completed the questionnaire. The disability weights ranged from 0.007 (95%UI: 0.003-0.012) for mild distance vision impairment to 0.741 (95% UI: 0.498-0.924) for intensive care unit admission. Spearman's correlation of probit coefficients between sub-groups based on respondent's characteristics were all above 0.95 (p < 0.001). Comparison of disability weights of 140 health states that were included in the Dutch and European disability weights study showed a high correlation (Spearman's correlation: 0.942; p < 0.001); however, for 76 (54.3%) health states the point estimate of the Dutch disability weight fell outside of the 95%UI of the European disability weights. CONCLUSIONS: Respondent's characteristics had no influence on health state valuations with the paired comparison. However, comparison of the Dutch disability weights to the European disability weights indicates that health state preferences of the general population of the Netherlands differ from those of other European countries.
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Pessoas com Deficiência , Humanos , Países Baixos , Pessoa de Meia-Idade , Adulto , Feminino , Masculino , Estudos Transversais , Idoso , Adolescente , Adulto Jovem , Inquéritos e Questionários , Avaliação da Deficiência , Nível de SaúdeRESUMO
BACKGROUND: The burden of disease (BOD) approach, originating with the Global Burden of Disease (GBD) study in the 1990s, has become a cornerstone for population health monitoring. Despite the widespread use of the Disability-Adjusted Life Year (DALY) metric, variations in methodological approaches and reporting inconsistencies hinder comparability across studies. To tackle this issue, we set out to develop guidelines for reporting DALY calculation studies to improve the transparency and comparability of BOD estimates. METHODS AND FINDINGS: The development of the STROBOD statement began within the European Burden of Disease Network, evolving from initial concepts discussed in workshops and training sessions focused on critical analysis of BOD studies. In 2021, a working group was formed to refine the preliminary version into the final Standardised Reporting of Burden of Disease studies (STROBOD) statement, consisting of 28 items structured across six main sections. These sections cover the title, abstract, introduction, methods, results, discussion, and open science, aiming to ensure transparency and standardization in reporting BOD studies. Notably, the methods section of the STROBOD checklist encompasses aspects such as study setting, data inputs and adjustments, DALY calculation methods, uncertainty analyses, and recommendations for reproducibility and transparency. A pilot phase was conducted to test the efficacy of the STROBOD statement, highlighting the importance of providing clear explanations and examples for each reporting item. CONCLUSIONS: The inaugural STROBOD statement offers a crucial framework for standardizing reporting in BOD research, with plans for ongoing evaluation and potential revisions based on user feedback. While the current version focuses on general BOD methodology, future iterations may include specialized checklists for distinct applications such as injury or risk factor estimation, reflecting the dynamic nature of this field.
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Efeitos Psicossociais da Doença , Humanos , Anos de Vida Ajustados por Deficiência , Carga Global da Doença , Lista de Checagem , Projetos de Pesquisa/normas , Reprodutibilidade dos Testes , Guias como AssuntoRESUMO
BACKGROUND: Exposure to high levels of environmental air pollution causes several health outcomes and has been associated with increased mortality, premature mortality, and morbidity. Ambient exposure to PM2.5 is currently considered the leading environmental risk factor globally. A causal relationship between exposure to PM2.5 and the contribution of this exposure to cardiovascular morbidity and mortality was already demonstrated by the American Heart Association. METHODS: To estimate the burden of mortality attributable to environmental risk factors, a comparative risk assessment was performed, considering a "top-down" approach. This approach uses an existing estimate of mortality of the disease endpoint by all causes as a starting point. A population attributable fraction was calculated for the exposure to PM2.5the overall burden of IHD and stroke was multiplied by the PAF to determine the burden attributable to this risk factor. The avoidable burden was calculated using the potential impact fraction (PIF) and considering the WHO-AQG 2021 as an alternative scenario. RESULTS: Between 2011 and 2021, the ambient exposure to PM2.5 resulted in a total of 288,862.7 IHD YLL and a total of 420,432.3 stroke YLL in Portugal. This study found a decreasing trend in the mortality burden attributable to PM2.5 exposure, for both males and females and different age-groups. For different regions of Portugal, the same trend was observed in the last years. The mortality burden attributable to long-term exposure to PM2.5 was mainly concentrated in Lisbon Metropolitan Area, North and Centre. Changes in the exposure limits to the WHO recommended value of exposure (WHO-AQG 2021) have a reduction in the mortality burden due to IHD and stroke attributable to PM2.5 exposure, in Portugal. CONCLUSION: Between 2011 and 2021, approximately 22% and 23% of IHD and stroke deaths were attributable to PM2.5 exposure. Nevertheless, the mortality burden attributable to cardiovascular diseases has been decreasing in last years in Portugal. Our findings provide evidence of the impact of air pollution on human health, which are crucial for decision-making, at the national and regional level.
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Doenças Cardiovasculares , Exposição Ambiental , Material Particulado , Humanos , Portugal/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Masculino , Feminino , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Pessoa de Meia-Idade , Exposição Ambiental/efeitos adversos , Adulto , Medição de Risco , Idoso de 80 Anos ou mais , Adulto Jovem , Efeitos Psicossociais da Doença , Poluição do Ar/efeitos adversos , Adolescente , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/epidemiologia , CriançaRESUMO
This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.
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Doenças Transmissíveis , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Doenças Transmissíveis/epidemiologia , Europa (Continente)/epidemiologia , Reino Unido/epidemiologia , Países Baixos , Efeitos Psicossociais da DoençaRESUMO
BACKGROUND: Although overall health status in the last decades improved, health inequalities due to non-communicable diseases (NCDs) persist between and within European countries. There is a lack of studies giving insights into health inequalities related to NCDs in the European Economic Area (EEA) countries. Therefore, the aim of the present study was to quantify health inequalities in age-standardized disability adjusted life years (DALY) rates for NCDs overall and 12 specific NCDs across 30 EEA countries between 1990 and 2019. Also, this study aimed to determine trends in health inequalities and to identify those NCDs where the inequalities were the highest. METHODS: DALY rate ratios were calculated to determine and compare inequalities between the 30 EEA countries, by sex, and across time. Annual rate of change was used to determine the differences in DALY rate between 1990 and 2019 for males and females. The Gini Coefficient (GC) was used to measure the DALY rate inequalities across countries, and the Slope Index of Inequality (SII) to estimate the average absolute difference in DALY rate across countries. RESULTS: Between 1990 and 2019, there was an overall declining trend in DALY rate, with larger declines among females compared to males. Among EEA countries, in 2019 the highest NCD DALY rate for both sexes were observed for Bulgaria. For the whole period, the highest DALY rate ratios were identified for digestive diseases, diabetes and kidney diseases, substance use disorders, cardiovascular diseases (CVD), and chronic respiratory diseases - representing the highest inequality between countries. In 2019, the highest DALY rate ratio was found between Bulgaria and Iceland for males. GC and SII indicated that the highest inequalities were due to CVD for most of the study period - however, overall levels of inequality were low. CONCLUSIONS: The inequality in level 1 NCDs DALYs rate is relatively low among all the countries. CVDs, digestive diseases, diabetes and kidney diseases, substance use disorders, and chronic respiratory diseases are the NCDs that exhibit higher levels of inequality across countries in the EEA. This might be mitigated by applying tailored preventive measures and enabling healthcare access.
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Doenças Cardiovasculares , Doenças não Transmissíveis , Doenças Respiratórias , Masculino , Feminino , Humanos , Expectativa de Vida , Anos de Vida Ajustados por Qualidade de Vida , Doenças não Transmissíveis/epidemiologia , Carga Global da Doença , Doenças Cardiovasculares/epidemiologia , Doenças Respiratórias/epidemiologia , Saúde GlobalRESUMO
BACKGROUND: It is important to understand the effects of population ageing on disease burden and explore conditions that drive poor health in later life to prevent or manage these. We examined the development of disease burden and its components for major disease groups among older adults in Europe over the last 30 years. METHODS: Using data from the Global Burden of Disease 2019 Study, we analyzed burden of disease trends between 1990 and 2019 measured by years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALYs) among older adults (65+ years) in Western, Central and Eastern Europe using cause groups for diseases and injuries. RESULTS: Between 1990 and 2019, the crude numbers of DALYs for all causes increased substantially among older Western Europeans. In Eastern Europe, the absolute DALYs also increased from 1990 to 2005 but then decreased between 2006 and 2013. However, DALY rates declined for all European regions over time, with large differences in the magnitude by region and gender. Changes in the YLL rate were mainly driven by the contribution of cardiovascular diseases. CONCLUSIONS: This study found an increased overall absolute disease burden among older Europeans between 1990 and 2019. The demographic change that has taken place in Eastern European countries implies a potential problem of directed resource allocation to the health care sector. Furthermore, the findings highlight the potential health gains through directing resources to health promotion and treatment to reduce YLDs and to prevent YLLs, primarily from cardiovascular diseases.
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Doenças Cardiovasculares , Pessoas com Deficiência , Carga Global da Doença , Mortalidade , Idoso , Humanos , Efeitos Psicossociais da Doença , Europa (Continente)/epidemiologia , Saúde Global , Expectativa de Vida , Anos de Vida Ajustados por Qualidade de Vida , Mortalidade/tendências , Anos de Vida Ajustados por DeficiênciaRESUMO
BACKGROUND: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. METHODS: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. RESULTS: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. CONCLUSIONS: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.
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Efeitos Psicossociais da Doença , Pessoas com Deficiência , Europa (Continente)/epidemiologia , Carga Global da Doença , Humanos , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Assessment of disability-adjusted life years (DALYs) resulting from non-communicable diseases (NCDs) requires specific calculation methods and input data. The aims of this study were to (i) identify existing NCD burden of disease (BoD) activities in Europe; (ii) collate information on data sources for mortality and morbidity; and (iii) provide an overview of NCD-specific methods for calculating NCD DALYs. METHODS: NCD BoD studies were systematically searched in international electronic literature databases and in grey literature. We included all BoD studies that used the DALY metric to quantify the health impact of one or more NCDs in countries belonging to the European Region. RESULTS: A total of 163 BoD studies were retained: 96 (59%) were single-country or sub-national studies and 67 (41%) considered more than one country. Of the single-country studies, 29 (30%) consisted of secondary analyses using existing Global Burden of Disease (GBD) results. Mortality data were mainly derived (49%) from vital statistics. Morbidity data were frequently (40%) drawn from routine administrative and survey datasets, including disease registries and hospital discharge databases. The majority (60%) of national BoD studies reported mortality corrections. Multimorbidity adjustments were performed in 18% of national BoD studies. CONCLUSION: The number of national NCD BoD assessments across Europe increased over time, driven by an increase in BoD studies that consisted of secondary data analysis of GBD study findings. Ambiguity in reporting the use of NCD-specific BoD methods underlines the need for reporting guidelines of BoD studies to enhance the transparency of NCD BoD estimates across Europe.
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Doenças não Transmissíveis , Europa (Continente)/epidemiologia , Carga Global da Doença , Saúde Global , Humanos , Armazenamento e Recuperação da Informação , Doenças não Transmissíveis/epidemiologia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Initiatives aiming to assess the impact of rare diseases on population health might be hampered due to the complexity of disability-adjusted life years (DALYs) estimation. This study aimed to give insight into the epidemiological data sources and methodological approaches used in studies that estimated DALYs for chronic non-communicable rare diseases (CNCRD), and compare its results. METHODS: A literature strategy was developed for peer-review search in Embase and Medline, and also performed on grey literature databases and population health and/or rare disease-focused websites. We included studies that determined the burden of CNCRD listed on the Orphanet's and/or the Genetic and Rare Diseases information center (GARD) websites. We excluded communicable and occupational diseases, rare cancers, and cost-effectiveness/benefit studies. Two researchers independently screened the identified records and extracted data from the final included studies. We used the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) statement to assess the quality of reporting of the included studies. The data synthesis depicted the studies' characteristics, their distribution by geographic coverage and the group of disease(s) they focused on, the methods and data input sources used and estimated DALY per case. RESULTS: In total, 533 titles were screened, and 18 studies were included. These studies covered 19 different CNCRDs, of which most fell in the disease category "Diseases of the nervous system". Diverse methodological approaches and data input sources were observed among burden of CNCRD studies. A wide range of DALY per case was observed across the different studies and diseases included. CONCLUSIONS: A low number of burden of CNCRD studies was observed and most estimates resulted from multi-country studies, underlining the importance of international cooperation to further CNCRD research. This study revealed a lack of epidemiological data and harmonization of methods which hampers comparisons across burden of CNCRD studies.
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Anos de Vida Ajustados por Deficiência , Doenças Raras , Humanos , Doenças Raras/epidemiologia , Doenças não Transmissíveis/epidemiologia , Doença Crônica , Efeitos Psicossociais da Doença , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Health inequalities have been associated with shorter lifespans. We aimed to investigate subnational geographical inequalities in all-cause years of life lost (YLLs) and the association between YLLs and socioeconomic factors, such as household income, risk of poverty, and educational attainment, in countries within the European Economic Area (EEA) before the COVID-19 pandemic. METHODS: In this ecological study, we extracted demographic and socioeconomic data from Eurostat for 1390 small regions and 285 basic regions for 32 countries in the EEA, which was complemented by a time-trend analysis of subnational regions within the EEA. Age-standardised YLL rates per 100 000 population were estimated from 2009 to 2019 based on methods from the Global Burden of Disease study. Geographical inequalities were assessed using the Gini coefficient and slope index of inequality. Socioeconomic inequalities were assessed by investigating the association between socioeconomic factors (educational attainment, household income, and risk of poverty) and YLLs in 2019 using negative binomial mixed models. FINDINGS: Between Jan 1, 2009, and Dec 31, 2019, YLLs lowered in almost all subnational regions. The Gini coefficient of YLLs across all EEA regions was 14·2% (95% CI 13·6-14·8) for females and 17·0% (16·3 to 17·7) for males. Relative geographical inequalities in YLLs among women were highest in the UK (Gini coefficient 11·2% [95% CI 10·1-12·3]) and among men were highest in Belgium (10·8% [9·3-12·2]). The highest YLLs were observed in subnational regions with the lowest levels of educational attainment (incident rate ratio [IRR] 1·19 [1·13-1·26] for females; 1·22 [1·16-1·28] for males), household income (1·35 [95% CI 1·19-1·53]), and the highest poverty risk (1·25 [1·18-1·34]). INTERPRETATION: Differences in YLLs remain within, and between, EEA countries and are associated with socioeconomic factors. This evidence can assist stakeholders in addressing health inequities to improve overall disease burden within the EEA. FUNDING: Research Council of Norway; Development, and Innovation Fund of Hungary; Norwegian Institute of Public Medicine; and COST Action 18218 European Burden of Disease Network.
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Expectativa de Vida , Pandemias , Masculino , Humanos , Feminino , Fatores Socioeconômicos , Europa (Continente)/epidemiologia , PobrezaRESUMO
Previous efforts to estimate the burden of fatigue-related symptoms due to long COVID have a very high threshold for inclusion of cases, relative to the proposed definition from the World Health Organization. In practice this means that milder cases, that may be occurring very frequently, are not included in estimates of the burden of long COVID which will result in underestimation. A more comprehensive approach to modelling the disease burden from long COVID, in relation to fatigue, can ensure that we do not only focus on what is easiest to measure; which risks losing focus of less severe health states that may be more difficult to measure but are occurring very frequently. Our proposed approach provides a means to better understand the scale of challenge from long COVID, for consideration when preventative and mitigative action is being planned.
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OBJECTIVES: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. METHODS: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. RESULTS: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. CONCLUSIONS: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates. REGISTRATION: The study protocol has been registered on PROSPERO, CRD42020177477 (available at: https://www.crd.york.ac.uk/PROSPERO/ ).
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SARS-CoV and MERS-CoV Macro Domains (MDs) exhibit topological and conformational features that resemble the nsP3b macro (or "X") domain of SARS-CoV-2. Indeed, all the three domains (SARS-CoV-2, SARS-CoV and MERS-CoV MDs) fold in a three-layer α/ß/α sandwich structure, as reported by crystallographic structural investigation of SARS-CoV MD and MERS-CoV MD. These viral MDs are able to bind ADP-ribose as many other MDs from different kingdoms. They have been characterized also as de-ADP-ribosylating enzymes. For this reason, these viral macrodomains recently emerged as important drug targets since they can counteract antiviral ADP-ribosylation mediated by poly-ADP-ribose polymerase (PARPs). Even in presence of the 3D structures of SARS-CoV MD and of MERS-CoV MD, we report herein the almost complete NMR backbone (1H, 13C, 15N) of SARS-CoV MD and MERS-CoV proteins in the free and ADPr bound forms, and the NMR chemical shift-based prediction of their secondary structure elements. These NMR data will help to further understanding of the atomic-level conformational dynamics of these proteins and will allow an extensive screening of small molecules as potential antiviral drugs.
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COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Adenosina Difosfato Ribose/metabolismo , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/química , Ressonância Magnética Nuclear Biomolecular , Domínios Proteicos , SARS-CoV-2RESUMO
BACKGROUND: The disability weight is an essential factor to estimate the healthy time that is lost due to living with a certain state of illness. A 2014 review showed a considerable variation in methods used to derive disability weights. Since then, several sets of disability weights have been developed. This systematic review aimed to provide an updated and comparative overview of the methodological design choices and surveying techniques that have been used in disability weights measurement studies and how they evolved over time. METHODS: A literature search was conducted in multiple international databases (early-1990 to mid-2021). Records were screened according to pre-defined eligibility criteria. The quality of the included disability weights measurement studies was assessed using the Checklist for Reporting Valuation Studies (CREATE) instrument. Studies were collated by characteristics and methodological design approaches. Data extraction was performed by one reviewer and discussed with a second. RESULTS: Forty-six unique disability weights measurement studies met our eligibility criteria. More than half (n = 27; 59%) of the identified studies assessed disability weights for multiple ill-health outcomes. Thirty studies (65%) described the health states using disease-specific descriptions or a combination of a disease-specific descriptions and generic-preference instruments. The percentage of studies obtaining health preferences from a population-based panel increased from 14% (2004-2011) to 32% (2012-2021). None of the disability weight studies published in the past 10 years used the annual profile approach. Most studies performed panel-meetings to obtain disability weights data. CONCLUSIONS: Our review reveals that a methodological uniformity between national and GBD disability weights studies increased, especially from 2010 onwards. Over years, more studies used disease-specific health state descriptions in line with those of the GBD study, panel from general populations, and data from web-based surveys and/or household surveys. There is, however, a wide variation in valuation techniques that were used to derive disability weights at national-level and that persisted over time.
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hPARP14 is a human ADP-ribosyl-transferase (ART) that belongs to the macroPARPs family, together with hPARP9 and hPARP15. It contains a tandem of three macro domains (MD) while each of them has different properties. The first one, namely MD1, has not been reported to exhibit a high binding affinity for ADP-ribose (ADPr) in contrast to the following two (MD2 and MD3). All three MDs exhibit an α/ß/α sandwich-like fold as reported by the deposited crystallographic structures. MD2 and MD3 recognize mono-ADP-ribosylated (MARylated) but not poly-ADP-ribosylated (PARylated) substrates and thus they allow hPARP14 to bind its targets, which can be potentially MARylated by its catalytic domain (CD). hPARP14 participates in DNA damage repair process and immune response against viruses like SARS-CoV-2, which also harbors an MD fold. Furthermore, hPARP14 like the other two macroPARPs (hPARP9 and hPARP15), is implicated in numerous types of cancer, such as B-aggressive lymphoma and sarcoma, rendering its MDs as potential important drug targets. Herein, we report the complete NMR backbone and side chain assignment (1H, 13C, 15N) of hPARP14 MD2 in the free and ADPr bound states and the NMR chemical shift-based prediction of its secondary structure elements. This is the first reported NMR study of a hPARP macro domain, paving the way to screen by NMR chemical compounds which may alter the ability of hPARP14 to interact with its substrates affecting its function.
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COVID-19 , Proteínas Nucleares/química , SARS-CoV-2 , Adenosina Difosfato Ribose/metabolismo , Humanos , Ressonância Magnética Nuclear Biomolecular , TransferasesRESUMO
Objectives: Quantifying the combined impact of morbidity and mortality is a key enabler to assessing the impact of COVID-19 across countries and within countries relative to other diseases, regions, or demographics. Differences in methods, data sources, and definitions of mortality due to COVID-19 may hamper comparisons. We describe efforts to support countries in estimating the national-level burden of COVID-19 using disability-adjusted life years. Methods: The European Burden of Disease Network developed a consensus methodology, as well as a range of capacity-building activities to support burden of COVID-19 studies. These activities have supported 11 national studies so far, with study periods between January 2020 and December 2021. Results: National studies dealt with various data gaps and different assumptions were made to face knowledge gaps. Still, they delivered broadly comparable results that allow for interpretation of consistencies, as well as differences in the quantified direct health impact of the pandemic. Discussion: Harmonized efforts and methodologies have allowed for comparable estimates and communication of results. Future studies should evaluate the impact of interventions, and unravel the indirect health impact of the COVID-19 crisis.
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COVID-19 , COVID-19/epidemiologia , Efeitos Psicossociais da Doença , Humanos , Morbidade , Pandemias , Anos de Vida Ajustados por Qualidade de VidaRESUMO
BACKGROUND: Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. METHODS: We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. RESULTS: In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. CONCLUSIONS: Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.
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OBJECTIVE: The age-standardized prevalence of cardiovascular diseases (CVDs) among the Cypriot population in 2017 was estimated to be 5552 per 100,000. Therefore, the CVD prevention in Cyprus is of paramount importance. Pharmacists are one of the most accessible health-care professionals (HCPs) and the first port of call for the public. In Cyprus, there are 55.59 pharmacies per 100,000 inhabitants. Therefore, the role of Cypriot pharmacists (CPs) in primary CVD prevention is essential. This study aimed to explore both the existing and potential future roles of CPs in CVD prevention. METHODS: A descriptive qualitative study employing structured interviews (SIs) was conducted. Initially, the CPs were identified through a list provided by the Cypriot Pharmaceutical Services. The researcher(s) then contacted CPs by telephone. Face-to-face interviews were scheduled based on the CP's availability. In total, 21 SIs were transcribed verbatim, coded, and analyzed thematically. SIs continued until data saturation was achieved. FINDINGS: The findings are reported under the themes of pharmacists' knowledge and role, resources/tools available and training, communication and relations, and barriers. CPs expressed the need for training, and they are ready to have a more proactive role within the primary health care. The main barrier identified was the lack of responsiveness of the public and the lack of CP's time. CONCLUSION: CPs have the potential to actively participate in CVD prevention in Cyprus. CPs want to start offering primary CVD health services, with the smoking cessation being the first intervention.
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BACKGROUND: Non-communicable diseases (NCDs) accounted for over 90% of all deaths in the Cypriot population, in 2018. However, a detailed and comprehensive overview of the impact of NCDs on population health of Cyprus over the period of 1990 to 2017, expressed in disability-adjusted life years (DALYs), is currently not available. Knowledge about the drivers of changes in NCD DALYs over time is paramount to identify priorities for the prevention of NCDs in Cyprus and guide evidence-based decision making. The objectives of this paper were to: 1) assess the burden of NCDs in terms of years of life lost (YLLs), years lived with disability (YLDs), and DALYs in Cyprus in 2017, and 2) identify changes in the burden of NCDs in Cyprus over the 28-year period and assess the main drivers of these changes. METHODS: We performed a secondary database descriptive study using the Global Burden of Disease (GBD) 2017 results on NCDs for Cyprus from 1990 to 2017. We calculated the percentage change of age-standardized DALY rates between 1990 and 2017 and decomposed these time trends to assess the causes of death and disability that were the main drivers of change. RESULTS: In Cyprus in 2017, 83% (15,129 DALYs per 100,000; 12,809 to 17,707 95%UI) of total DALYs were due to NCDs. The major contributors to NCD DALYs were cardiovascular diseases (16.5%), neoplasms (16.3%), and musculoskeletal disorders (15.6%). Between 1990 and 2017, age-standardized NCD DALY rates decreased by 23%. For both males and females, the largest decreases in DALY rates were observed in ischemic heart disease and stroke. For Cypriot males, the largest increases in DALY rates were observed for pancreatic cancer, drug use disorders, and acne vulgaris, whereas for Cypriot females these were for acne vulgaris, psoriasis and eating disorders. CONCLUSION: Despite a decrease in the burden of NCDs over the period from 1990 to 2017, NCDs are still a major public health challenge. Implementation of interventions and early detection screening programmes of modifiable NCD risk factors are needed to reduce occurrence and exacerbation of leading causes of NCDs in the Cypriot population.