The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis.

BACKGROUND: Rotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries. METHODS: Beginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars. RESULTS: Vaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147-$38,993) and ranged from $85 per DALY averted (95% UI: $13-$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030-$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39-$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382-$3,118). CONCLUSION: Our findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Cost-effectiveness of HPV vaccination in 195 countries: A meta-regression analysis.

Cost-effectiveness analysis (CEA) is a well-known, but resource intensive, method for comparing the costs and health outcomes of health interventions. To build on available evidence, researchers are developing methods to transfer CEA across settings; previous methods do not use all available results nor quantify differences across settings. We conducted a meta-regression analysis of published CEAs of human papillomavirus (HPV) vaccination to quantify the effects of factors at the country, intervention, and method-level, and predict incremental cost-effectiveness ratios (ICERs) for HPV vaccination in 195 countries. We used 613 ICERs reported in 75 studies from the Tufts University's Cost-Effectiveness Analysis (CEA) Registry and the Global Health CEA Registry, and extracted an additional 1,215 one-way sensitivity analyses. A five-stage, mixed-effects meta-regression framework was used to predict country-specific ICERs. The probability that HPV vaccination is cost-saving in each country was predicted using a logistic regression model. Covariates for both models included methods and intervention characteristics, and each country's cervical cancer burden and gross domestic product per capita. ICERs are positively related to vaccine cost, and negatively related to cervical cancer burden. The mean predicted ICER for HPV vaccination is 2017 US$4,217 per DALY averted (95% uncertainty interval (UI): US$773-13,448) globally, and below US$800 per DALY averted in 64 countries. Predicted ICERs are lowest in Sub-Saharan Africa and South Asia, with a population-weighted mean ICER across 46 countries of US$706 per DALY averted (95% UI: $130-2,245), and across five countries of US$489 per DALY averted (95% UI: $90-1,557), respectively. Meta-regression analyses can be conducted on CEA, where one-way sensitivity analyses are used to quantify the effects of factors at the intervention and method-level. Building on all published results, our predictions support introducing and expanding HPV vaccination, especially in countries that are eligible for subsidized vaccines from GAVI, the Vaccine Alliance, and Pan American Health Organization.

National burden of cancer in Italy, 1990-2017: a systematic analysis for the global burden of disease study 2017.

We monitored the burden of cancer in Italy and its trends over the last three decades, providing estimates of cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs), for cancer overall and 30 cancer sites using data from the Global Burden of Disease study 2017. An overview of mortality trends between 1990 and 2017 was also provided. In 2017, there were 254,336 new cancer cases in men and 214,994 in women, corresponding to an age-standardized incidence rate (ASIR) of 438 and 330/100,000, respectively. Between 1990 and 2017, incident cancer cases, and, to a lesser extent, ASIRs significantly increased overall and for almost all cancer sites, but ASIRs significantly declined for lung and other tobacco-related neoplasms. In 2017, there were 101,659 cancer deaths in men (age-standardized death rate, ASDR, 158.5/100,000) and 78,918 in women (ASDR 93.9/100,000). Cancer deaths significantly increased between 1990 and 2017 (+ 18%), but ASDR significantly decreased (- 28%). Deaths significantly increased for many cancer sites, but decreased for stomach, esophageal, laryngeal, Hodgkin lymphoma, and testicular cancer. ASDRs significantly decreased for most neoplasms, with the main exceptions of cancer of the pancreas and uterus, and multiple myeloma. In 2017, cancer caused 3,204,000 DALYs. Between 1990 and 2017, DALYs and age-standardized DALY rates significantly declined (-3.4% and -33%, respectively). Age-standardized mortality rates in Italy showed favorable patterns over the last few decades. However, the absolute number of cancer cases and, to a lower extent, of cancer deaths increased likely due to the progressive ageing of the population, this calling for a continuous effort in cancer prevention, early diagnosis, and treatment.

Vector bionomics and vectorial capacity as emergent properties of mosquito behaviors and ecology.

Mosquitoes are important vectors for pathogens that infect humans and other vertebrate animals. Some aspects of adult mosquito behavior and mosquito ecology play an important role in determining the capacity of vector populations to transmit pathogens. Here, we re-examine factors affecting the transmission of pathogens by mosquitoes using a new approach. Unlike most previous models, this framework considers the behavioral states and state transitions of adult mosquitoes through a sequence of activity bouts. We developed a new framework for individual-based simulation models called MBITES (Mosquito Bout-based and Individual-based Transmission Ecology Simulator). In MBITES, it is possible to build models that simulate the behavior and ecology of adult mosquitoes in exquisite detail on complex resource landscapes generated by spatial point processes. We also developed an ordinary differential equation model which is the Kolmogorov forward equations for models developed in MBITES under a specific set of simplifying assumptions. While mosquito infection and pathogen development are one possible part of a mosquito's state, that is not our main focus. Using extensive simulation using some models developed in MBITES, we show that vectorial capacity can be understood as an emergent property of simple behavioral algorithms interacting with complex resource landscapes, and that relative density or sparsity of resources and the need to search can have profound consequences for mosquito populations' capacity to transmit pathogens.

Funding and services needed to achieve universal health coverage: applications of global, regional, and national estimates of utilisation of outpatient visits and inpatient admissions from 1990 to 2016, and unit costs from 1995 to 2016.

BACKGROUND: To inform plans to achieve universal health coverage (UHC), we estimated utilisation and unit cost of outpatient visits and inpatient admissions, did a decomposition analysis of utilisation, and estimated additional services and funds needed to meet a UHC standard for utilisation. METHODS: We collated 1175 country-years of outpatient data on utilisation from 130 countries and 2068 country-years of inpatient data from 128 countries. We did meta-regression analyses of annual visits and admissions per capita by sex, age, location, and year with DisMod-MR, a Bayesian meta-regression tool. We decomposed changes in total number of services from 1990 to 2016. We used data from 795 National Health Accounts to estimate shares of outpatient and inpatient services in total health expenditure by location and year and estimated unit costs as expenditure divided by utilisation. We identified standards of utilisation per disability-adjusted life-year and estimated additional services and funds needed. FINDINGS: In 2016, the global age-standardised outpatient utilisation rate was 5·42 visits (95% uncertainty interval [UI] 4·88-5·99) per capita and the inpatient utilisation rate was 0·10 admissions (0·09-0·11) per capita. Globally, 39·35 billion (95% UI 35·38-43·58) visits and 0·71 billion (0·65-0·77) admissions were provided in 2016. Of the 58·65% increase in visits since 1990, population growth accounted for 42·95%, population ageing for 8·09%, and higher utilisation rates for 7·63%; results for the 67·96% increase in admissions were 44·33% from population growth, 9·99% from population ageing, and 13·55% from increases in utilisation rates. 2016 unit cost estimates (in 2017 international dollars [I$]) ranged from I$2 to I$478 for visits and from I$87 to I$22 543 for admissions. The annual cost of 8·20 billion (6·24-9·95) additional visits and 0·28 billion (0·25-0·30) admissions in low-income and lower-middle income countries in 2016 was I$503·12 billion (404·35-605·98) or US$158·10 billion (126·58-189·67). INTERPRETATION: UHC plans can be based on utilisation and unit costs of current health systems and guided by standards of utilisation of outpatient visits and inpatient admissions that achieve the highest coverage of personal health services at the lowest cost. FUNDING: Bill & Melinda Gates Foundation.