Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.

In 2019, it was estimated that 10 million people died due to cancer worldwide.¹ While a relatively small percentage of global cancer deaths were caused by lip, oral cavity, and pharyngeal cancers (3.2%), there is broad variation in survival around the world,² and those who survive may have substantial reductions in their quality of life.^1,3 Reasons for differences in outcomes are multifactorial but likely include differences in access to early-stage detection and effective therapies, as well as potential differences in risk factor exposure patterns.¹ Established risk factors for oral and pharyngeal cancers are tobacco, alcohol, and betel quid consumption,^4,5 all of which increase cancer risk in a dose- and time-dependent fashion.^6,7 Infection with human papillomavirus (HPV) is also a known risk factor—established for oral cavity, tonsil, and oropharynx cancers^4,5—which is especially relevant in certain geographic areas of the world.^8,9

Objectives: Deep learning (DL) has been increasingly employed for automated landmark detection, e.g., for cephalometric purposes. We performed a systematic review and meta-analysis to assess the accuracy and underlying evidence for DL for cephalometric landmark detection on 2-D and 3-D radiographs. Methods: Diagnostic accuracy studies published in 2015-2020 in Medline/Embase/IEEE/arXiv and employing DL for cephalometric landmark detection were identified and extracted by two independent reviewers. Random-effects meta-analysis, subgroup, and meta-regression were performed, and study quality was assessed using QUADAS-2. The review was registered (PROSPERO no. 227498). Data: From 321 identified records, 19 studies (published 2017–2020), all employing convolutional neural networks, mainly on 2-D lateral radiographs (n=15), using data from publicly available datasets (n=12) and testing the detection of a mean of 30 (SD: 25; range.: 7–93) landmarks, were included. The reference test was established by two experts (n=11), 1 expert (n=4), 3 experts (n=3), and a set of annotators (n=1). Risk of bias was high, and applicability concerns were detected for most studies, mainly regarding the data selection and reference test conduct. Landmark prediction error centered around a 2-mm error threshold (mean; 95% confidence interval: (–0.581; 95 CI: –1.264 to 0.102 mm)). The proportion of landmarks detected within this 2-mm threshold was 0.799 (0.770 to 0.824). Conclusions: DL shows relatively high accuracy for detecting landmarks on cephalometric imagery. The overall body of evidence is consistent but suffers from high risk of bias. Demonstrating robustness and generalizability of DL for landmark detection is needed. Clinical significance: Existing DL models show consistent and largely high accuracy for automated detection of cephalometric landmarks. The majority of studies so far focused on 2-D imagery; data on 3-D imagery are sparse, but promising. Future studies should focus on demonstrating generalizability, robustness, and clinical usefulness of DL for this objective.