Клинико-эпидемиологические особенности проявлений папилломавирусной инфекции на примере рака шейки матки и аногенитальных (венерических) бородавок

Background: Cervical cancer and genital warts (GWs) are some of the most common manifestations of human papillomavirus infection (HPV). These lesions cause significant damage to the reproductive health of the population, which leads to increased attention to the prevention of HPV infection among various population groups. Aims: To determine the clinical and epidemiological features of the HPV manifestations by the example of cervical cancer and genital warts. Methods: A retrospective analysis of anamnestic information of 115 women with an established diagnosis of cervical cancer and 177 patients with an established diagnosis of GWs was performed. The clinical and epidemiological characteristics of patients with diagnoses of GWs and cervical cancer were based on the development of outpatient admission cards and inpatient histories, as well as test data for HPV. Results: HPV 16 was the most common HPV type among patients with GWs and cervical cancer ― it was detected in 37.6% of cases. Also the most frequently encountered: HPV 6/18/11/31/51/52. In 43.2% cases of HPV detection, two or more types were detected at once, the most common combinations: HPV16 and HPV18, HPV6 and HPV16, HPV6 and HPV11. Analysis of the frequency of screening for cervical cancer and visits to the gynecologist for 5 years before establishing the diagnosis showed that among those who did not screen for cervical cancer, the risk of diagnosing stage IIIV was 5.2 times higher than among individuals who underwent cervical screening 2 years ago, or once a year for the last five years. Among patients with GWs who had 2 or more sexual partners for 1 year, 13.5% of patients regularly used barrier contraception methods (condoms) during sexual contact, not regularly ― 61.5%, did not use them at all ― 25.0%. Conclusions: Identifying the clinical and epidemiological features of HPV infection should contribute to the development of new and optimize existing prevention programs for a wide range of HPV-associated diseases.Обоснование. Рак шейки матки (РШМ) и аногенитальные (венерические) бородавки являются наиболее распространенными проявлениями папилломавирусной инфекции. Данные поражения наносят существенный ущерб репродуктивному здоровью населения, что обусловливает повышенное внимание к вопросам профилактики папилломавирусной инфекции среди различных групп населения. Цель исследования ― определение отдельных клинико-эпидемиологических особенностей папилломавирусной инфекции на примере рака шейки матки и аногенитальных (венерических) бородавок. Методы. Выполнено ретроспективное исследование; объектом исследования были пациенты с диагнозами РШМ и аногенитальных (венерических) бородавок, обратившиеся за медицинской помощью в период с 2015 по 2018 г. Данные получены с помощью сбора информации из медицинских карт стационарного больного (форма 003/у) и медицинских карт пациента, получающего медицинскую помощь в амбулаторных условиях (форма 025/у). Методы анализа и обработки материала ― аналитический и статистический. Результаты. В рамках исследования были проанализированы 292 карты пациентов, обратившихся за медицинской помощью. Наиболее часто ― в 37,6% случаев ― у пациентов с аногенитальными бородавками и РШМ при лабораторном обследовании выявлялся вирус папилломы человека (ВПЧ) 16-го типа. Также часто встречались ВПЧ 6/18/11/31/51/52. В 43,2% случаев определялись одновременно два и более типов ВПЧ, при этом наиболее частыми сочетаниями были ВПЧ16 и ВПЧ18, ВПЧ6 и ВПЧ16, ВПЧ6 и ВПЧ11. Проведенный анализ частоты скрининга на РШМ и посещения врача-гинеколога в течение 5 лет до установления диагноза показал, что среди лиц, не проходивших скрининг на РШМ, или прошедших его при обнаружении заболевания, риск выявления диагноза на IIIV стадии был в 5,2 раза выше, чем среди лиц, которые проходили цервикальный скрининг 2 года назад или 1 раз в год в течение последних 5 лет. Среди всех пациентов с аногенитальными бородавками, имевших по два и более половых партнера в течение 1 года, о регулярном использовании методов барьерной контрацепции (презервативов) при половом контакте сообщили 13,5%, о нерегулярном использовании ― 61,5%; 25,0% пациентов вообще не задумывались о методах предохранения. Заключение. Выявление клинико-эпидемиологических особенностей папилломавирусной инфекции должно способствовать разработке новых и оптимизации существующих профилактических программ в отношении широкого спектра ВПЧ-ассоциированных заболеваний

The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Worldwide, both the incidence and death rates of pancreatic cancer are increasing. Evaluation of pancreatic cancer burden and its global, regional, and national patterns is crucial to policy making and better resource allocation for controlling pancreatic cancer risk factors, developing early detection methods, and providing faster and more effective treatments. Methods: Vital registration, vital registration sample, and cancer registry data were used to generate mortality, incidence, and disability-adjusted life-years (DALYs) estimates. We used the comparative risk assessment framework to estimate the proportion of deaths attributable to risk factors for pancreatic cancer: smoking, high fasting plasma glucose, and high body-mass index. All of the estimates were reported as counts and age-standardised rates per 100 000 person-years. 95% uncertainty intervals (UIs) were reported for all estimates. Findings: In 2017, there were 448 000 (95% UI 439 000\u2013456 000) incident cases of pancreatic cancer globally, of which 232 000 (210 000\u2013221 000; 51\ub79%) were in males. The age-standardised incidence rate was 5\ub70 (4\ub79\u20135\ub71) per 100 000 person-years in 1990 and increased to 5\ub77 (5\ub76\u20135\ub78) per 100 000 person-years in 2017. There was a 2\ub73 times increase in number of deaths for both sexes from 196 000 (193 000\u2013200 000) in 1990 to 441 000 (433 000\u2013449 000) in 2017. There was a 2\ub71 times increase in DALYs due to pancreatic cancer, increasing from 4\ub74 million (4\ub73\u20134\ub75) in 1990 to 9\ub71 million (8\ub79\u20139\ub73) in 2017. The age-standardised death rate of pancreatic cancer was highest in the high-income super-region across all years from 1990 to 2017. In 2017, the highest age-standardised death rates were observed in Greenland (17\ub74 [15\ub78\u201319\ub70] per 100 000 person-years) and Uruguay (12\ub71 [10\ub79\u201313\ub75] per 100 000 person-years). These countries also had the highest age-standardised death rates in 1990. Bangladesh (1\ub79 [1\ub75\u20132\ub73] per 100 000 person-years) had the lowest rate in 2017, and S\ue3o Tom\ue9 and Pr\uedncipe (1\ub73 [1\ub71\u20131\ub75] per 100 000 person-years) had the lowest rate in 1990. The numbers of incident cases and deaths peaked at the ages of 65\u201369 years for males and at 75\u201379 years for females. Age-standardised pancreatic cancer deaths worldwide were primarily attributable to smoking (21\ub71% [18\ub78\u201323\ub77]), high fasting plasma glucose (8\ub79% [2\ub71\u201319\ub74]), and high body-mass index (6\ub72% [2\ub75\u201311\ub74]) in 2017. Interpretation: Globally, the number of deaths, incident cases, and DALYs caused by pancreatic cancer has more than doubled from 1990 to 2017. The increase in incidence of pancreatic cancer is likely to continue as the population ages. Prevention strategies should focus on modifiable risk factors. Development of screening programmes for early detection and more effective treatment strategies for pancreatic cancer are needed. Funding: Bill & Melinda Gates Foundation

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

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

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

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

Mapping routine measles vaccination in low- and middle-income countries

The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)(1-4). Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)(5-8). Here we generated annual estimates of routine childhood MCV1 coverage at 5 x 5-km(2) pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.Peer reviewe

The global, regional, and national burden of colorectal cancer and its attributable risk factors in 195 countries and territories, 1990�2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Data about the global, regional, and country-specific variations in the levels and trends of colorectal cancer are required to understand the impact of this disease and the trends in its burden to help policy makers allocate resources. Here we provide a status report on the incidence, mortality, and disability caused by colorectal cancer in 195 countries and territories between 1990 and 2017. Methods Vital registration, sample vital registration, verbal autopsy, and cancer registry data were used to generate incidence, death, and disability-adjusted life-year (DALY) estimates of colorectal cancer at the global, regional, and national levels. We also determined the association between development levels and colorectal cancer age-standardised DALY rates, and calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. All of the estimates are reported as counts and age-standardised rates per 100 000 person-years, with some estimates also presented by sex and 5-year age groups. Findings In 2017, there were 1.8 million (95% UI 1.8-1.9) incident cases of colorectal cancer globally, with an age-standardised incidence rate of 23.2 (22.7-23.7) per 100 000 person-years that increased by 9.5% (4.5-13.5) between 1990 and 2017. Globally, colorectal cancer accounted for 896 000 (876 300-915 700) deaths in 2017, with an age-standardised death rate of 11.5 (11.3-11.8) per 100 000 person-years, which decreased between 1990 and 2017 (-13.5% [-18.4 to -10.0]). Colorectal cancer was also responsible for 19.0 million (18.5-19.5) DALYs globally in 2017, with an age-standardised rate of 235.7 (229.7-242.0) DALYs per 100 000 person-years, which decreased between 1990 and 2017 (-14.5% [-20.4 to -10.3]). Slovakia, the Netherlands, and New Zealand had the highest age-standardised incidence rates in 2017. Greenland, Hungary, and Slovakia had the highest age-standardised death rates in 2017. Numbers of incident cases and deaths were higher among males than females up to the ages of 80-84 years, with the highest rates observed in the oldest age group (>= 95 years) for both sexes in 2017. There was a non-linear association between the Socio-demographic Index and the Healthcare Access and Quality Index and age-standardised DALY rates. In 2017, the three largest contributors to DALYs at the global level, for both sexes, were diet low in calcium (20.5% [12.9-28.9]), alcohol use (15.2% [12.1-18.3]), and diet low in milk (14.3% [5.1-24.8]). Interpretation There is substantial global variation in the burden of colorectal cancer. Although the overall colorectal cancer age-standardised death rate has been decreasing at the global level, the increasing age-standardised incidence rate in most countries poses a major public health challenge across the world. The results of this study could be useful for policy makers to carry out cost-effective interventions and to reduce exposure to modifiable risk factors, particularly in countries with high incidence or increasing burden