Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Influence of expiratory positive airway pressure on cardiac autonomic modulation at rest and in submaximal exercise in COPD patients

The aim of this study was to evaluate the effect of expiratory positive airway pressure (EPAP) on heart rate variability (HRV) indices at rest and during 6-min walk test (6MWT) in chronic obstructive pulmonary disease (COPD) patients. Fifteen moderate to severe COPD patients were randomized and evaluated with and without (Non-EPAP) a 5 cmH2O EPAP device. Respiratory rate (RR) was collected at rest (5 min), during the 6MWT (5 min), and at recovery (5 min). Indices of HRV were computed in the time domain, in the frequency domain, and nonlinear analysis. For EPAP and Non-EPAP during the 6MWT, we found an increased mean heart rate (HR) (P=0.001; P=0.001) while mean RR (P=0.001; P=0.015) and RR tri index decreased (P=0.006; P=0.028). Peripheral oxygen saturation (P=0.019) increased at rest only in the EPAP group. In EPAP, correlations were found between forced expiratory volume in 1 s (FEV1) and low frequency (LF) sympathetic tonus (P=0.05; r=-0.49), FEV1 and high frequency (HF) parasympathetic tonus at rest (P=0.05; r=0.49), lactate at rest and LF during the 6MWT (P=0.02; r=-0.57), and lactate at rest and HF during 6MWT (P=0.02; r=0.56). Through a linear regression model, we found that lactate at rest explained 27% of the alterations of LF during 6MWT. The use of 5 cmH2O EPAP improved autonomic cardiac modulation and its complexity at rest in COPD patients. Although it did not influence the performance of the 6MWT, the EPAP device caused alterations in resting lactate concentration with an effect on sympatho-vagal control during the test

Requirements of digestible methionine + cystine for broiler chickens at 1 to 42 days of age Exigências de metionina + cistina digestível para frangos de corte de 1 a 42 dias de idade

The objective of this work was to estimate requirements of digestible methionine + cystine for broiler chickens from 1 to 42 days of age. It was carried out four experiments for each one of the following phases: pre-initial, initial, growing and final. The birds were distributed in a completely randomized experimental design, with six treatments and six replicates. Treatments consisted of a basal feed for each phase, deficient in digestible methionine + cystine and supplemented with DL-methionine to supply six levels of digestible methionine + cystine, resulting in different digestible methionine + cystine:digestible lysine ratios. In the pre-initial phase, levels of digestible methionine + cystine did not influence feed intake and feed conversion. However, weight gain responded in a quadratic way. In the initial phase, levels of digestible methionine + cystine had decreasing linear effect on feed intake whereas weight gain and feed conversion were influenced in a quadratic manner. In the growth and final phases, feed intake was not influenced by levels of digestible methionine + cystine, but weight gain and feed conversion presented quadratic response. The levels of 0.873; 0.755; 0.748 and 0.661% of digestible methionine + cystine in the diet or the daily intake of 183; 575; 1,104 and 1,212 mg of digestible methionine + cystine are recommended for the pre-initial, initial, growth and final phases, respectively, which corresponds to the ratios of 71; 70; 76 and 72% of digestible methionine + cystine to digestible lysine.<br>Objetivou-se estimar as exigências de metionina + cistina digestível para frangos de corte machos de 1 a 42 dias de idade. Foram realizados quatro experimentos para cada uma das fases: pré-inicial, inicial, crescimento e final. As aves foram distribuídas em delineamento inteiramente casualizado, com seis tratamentos e seis repetições. Os tratamentos consistiram de uma ração basal para cada fase, deficiente em metionina + cistina e suplementada com DL-metionina para fornecer seis níveis de metionina + cistina digestível, resultando em diferentes relações metionina + cistina digestível:lisina digestível. Na fase pré-inicial, os níveis de metionina + cistina digestível não influenciaram o consumo de ração e a conversão alimentar. No entanto, o ganho de peso respondeu de forma quadrática. Na fase inicial, os níveis de metionina + cistina digestível tiveram efeito linear decrescente sobre o consumo de ração, enquanto o ganho de peso e a conversão alimentar foram influenciados de forma quadrática. Nas fases de crescimento e final, o consumo de ração não foi influenciado pelos níveis de metionina + cistina digestível, porém o ganho de peso e a conversão alimentar apresentaram resposta quadrática. Recomendam-se os níveis de 0,873; 0,755; 0,748 e 0.661% de metionina + cistina na dieta ou o consumo diário de 183, 575, 1.104 e 1.212 mg de metionina + cistina digestível nas fases pré-inicial, inicial, crescimento e final, respectivamente, que correspondem às relações de 71, 70, 76 e 72% de metionina + cistina digestível:lisina digestível

Nutritional levels of digestible methionine + cystine to brown-egg laying hens from 50 to 66 weeks of age

The objective of this study was to determine the requirement of digestible methionine + cystine of brown-eggs laying hens from 50 to 66 weeks age at the end of the first production cycle. The design was completely randomized, with 150 Brown Shaver hens, which were distributed in five treatments with six replications of five birds each. Birds received a basal diet with 2857 kcal/kg metabolizable energy and 15.97% crude protein, supplemented with 0.132; 0.174, 0.215, 0.256 and 0.298% DL-methionine (98%), in order to provide 0.572, 0.613, 0.653, 0.693 and 0.734% digestible methionine + cystine. The levels of digestible methionine + digestible cystine followed, respectively, the relations of 67, 72, 77, 81 and 86% with lysine fixed at 0.851%. Feed intake, methionine + cystine intake, feed conversion per dozen eggs, egg weigth and mass, percentage of egg components, internal egg quality and weight gain were evaluated. Methionine + cystine levels showed a quadratic effect on feed conversion per dozen eggs and egg weight, a linear effect on feed conversion per kilogram of eggs and percentage of albumen. There was also a positive linear effect on yolk percentage. The methionine + cystine requirement was estimated at 0.572%, corresponding to 682 mg of digestible methionine + cystine/bird/day