13 research outputs found
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Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026
Background
The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.
Methods
In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.
Findings
In 2019, at the onset of the COVID-19 pandemic, US7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the 43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, 37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.
Interpretation
There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained
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Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation
Binding of Eu<sup>III</sup> to 1,2-Hydroxypyridinone-Modified Peptide Nucleic Acids
Substitution of a nucleobase pair with a pair of 1,2-hydroxypyridinone
(<b>1,2-HOPO</b>) ligands in the center of a 10-base-pair peptide
nucleic acid (PNA) duplex provides a strong binding site for Eu<sup>III</sup> as evidenced by UV thermal melting curves, UV titrations,
and luminescence spectroscopy. Eu<sup>III</sup> excitation spectra
and luminescence lifetime data are consistent with Eu<sup>III</sup> bound to both <b>1,2 HOPO</b> ligands in a <b>PNA-HOPO</b> duplex as the major species present in solution
The NiCEST Approach: Nickel(II) ParaCEST MRI Contrast Agents
Paramagnetic Ni(II) complexes are shown here to form
paraCEST MRI
contrast agents (paraCEST = paramagnetic chemical exchange saturation
transfer; NiCEST = Ni(II) based CEST agents). Three azamacrocycles
with amide pendent groups bind Ni(II) to form stable NiCEST contrast
agents including 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane
(<b>L1</b>), 1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane
(<b>L2</b>), and 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane
(<b>L3</b>). [Ni(<b>L3</b>)]<sup>2+</sup>, [Ni(<b>L1</b>)]<sup>2+</sup>, and [Ni(<b>L2</b>)]<sup>2+</sup> have CEST
peaks attributed to amide protons that are shifted 72, 76, and 76
ppm from the bulk water resonance, respectively. Both CEST MR images
and CEST spectroscopy show that [Ni(<b>L3</b>)]<sup>2+</sup> has the largest CEST effect in 100 mM NaCl, 20 mM HEPES pH
7.4 at 37 °C. This larger CEST effect is attributed to the sharper
proton resonances of the complex which arise from a rigid structure
and low relaxivity
Neck circumference is independently associated with relative systemic hypertension in young adults with sickle cell anaemia
Abstract Background A seemingly interesting observation in patients with sickle cell anaemia (SCA) is that they usually have lower systemic blood pressures (BP) and insulin resistance than persons in the general population in spite of chronic inflammation and vasculopathy. However, relative systemic hypertension (rHTN) has been linked to pulmonary hypertension, increased blood viscosity and renal insufficiency, which could indicate a risk of developing cardiometabolic disorder (CMD) in SCA. We therefore hypothesized that neck circumference (NC) and CMD marker; triglyceride glucose (TyG) index would independently predict rHTN in young adults with SCA in steady state. Methods We compared the anthropometrical, hematological, hemorheological and CMD markers between SCA patients with normal BP < 120/70 mmHg; nHTN, n = 65) and those with rHTN (BP ≥ 120/70 mmHg, n = 32). Results Our results showed that SCA with rHTN had significantly higher body weight, waist circumference, NC, plasma viscosity, systolic and diastolic BP. Results also indicated that NC (OR: 2.98; 95% CI 1.46 to 6.10, p < 0.01) was a predictor of rHTN in SCA independent of gender, age, weight, waist circumference, BMI, blood viscosity, triglyceride or TyG. A receiver operating characteristic curve analysis also showed that NC was the most efficient predictor of rHTN than other CMD markers. Conclusion The present study demonstrates that increased NC is a salient risk factors that is independently associated with rHTN in SCA. The finding therefore underscores the utility of NC in early detection and stratification of systemic hypertension, particularly in individuals with SCA
Factional Competition, Sociopolitical Development, and Settlement Cycling in Ìlàrè District ( ca
Seven-Coordinate Co<sup>II</sup>, Fe<sup>II</sup> and Six-Coordinate Ni<sup>II</sup> Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media
The
solution chemistry and solid-state structures of the Co<sup>II</sup>, Fe<sup>II</sup>, and Ni<sup>II</sup> complexes of 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane
(<b>L</b>) are reported as members of a new class of paramagnetic
chemical exchange saturation transfer (paraCEST) MRI contrast agents
that contain transition metal ions. Crystallographic data show that
nitrogen and oxygen donor atoms of the macrocyclic ligand coordinate
to the metal ions to generate complexes with distorted pentagonal
bipyramidal geometry for [Co(<b>L</b>)]Cl<sub>2</sub>·2H<sub>2</sub>O or [Fe(<b>L</b>)](CF<sub>3</sub>SO<sub>3</sub>)<sub>2</sub>. The Ni<sup>II</sup> complex [Ni(<b>L</b>)](CF<sub>3</sub>SO<sub>3</sub>)<sub>2</sub>·H<sub>2</sub>O features a
hexadentate ligand in a distorted octahedral geometry. The proton
NMR spectra of all three complexes show highly dispersed and relatively
sharp proton resonances. The complexes were further characterized
by monitoring their dissociation under biologically relevant conditions
including solutions containing phosphate and carbonate, ZnCl<sub>2</sub>, or acidic conditions. Solutions of the paraCEST agents in 20 mM <i>N</i>-(2-hydroxyethyl)piperazine-<i>N</i>′-ethanesulfonic
acid (pH 7.4) and 100 mM NaCl showed highly shifted and intense CEST
peaks at 59, 72, and 92 ppm away from bulk water for [Co(<b>L</b>)]<sup>2+</sup>, [Ni(<b>L</b>)]<sup>2+</sup>, and [Fe(<b>L</b>)]<sup>2+</sup>, respectively at 37 °C on a 11.7 T NMR
spectrometer. CEST spectra with corresponding rate constants for proton
exchange are reported in 4% agarose gel (w/w), rabbit serum, egg white,
or buffered solutions. CEST phantoms of 4 mM complex in buffer, 4%
agarose gel (w/w), or rabbit serum on a 4.7 T MRI scanner at 37 °C,
are compared. The most substantial change was observed for the reactive
[Ni(<b>L</b>)]<sup>2+</sup>, which showed reduced CEST contrast
in rabbit serum and egg white. The complexes with the least highly
shifted CEST peaks ([Co(<b>L</b>)]<sup>2+</sup> and [Ni(<b>L</b>)]<sup>2+</sup>) showed a reduction in CEST contrast in 4%
agarose gel (w/w) compared to that in buffered solutions, while the
CEST effect for [Fe(<b>L</b>)]<sup>2+</sup> in 4% agarose gel
(w/w) was not substantially different
Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation.</p