Global, regional, and national childhood cancer burden, 1990-2019: An analysis based on the Global Burden of Disease Study 2019.

INTRODUCTION: Cancer is the leading cause of death among children. OBJECTIVES: We report on the latest estimates of the burden of cancer among children at the global, regional, and national levels from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study 2019, children's cancer data were analyzed by sex, age, year, and location. Age-standardized rates were used to compare the burdens among regions and nations. Joinpoint analysis was applied to assess the temporal trend of the global childhood cancer burden. RESULTS: In 2019, 291,319 (95% uncertainty interval [UI], 254,239 to 331,993) new cases and 98,834 (86,124 to 113,581) deaths from childhood cancer were documented globally. Further, 8,302,464 (7,230,447 to 9,555,118) DALYs and 1,806,630 (1,567,808 to 2,089,668) prevalent cases were recorded in the same year. Age-standardized incidence and prevalence rates of childhood cancer were greatest in higher SDI settings and increased most significantly in Australasia and Southern Latin America over the last 30 years. However, although age-standardized death and DALY rates of childhood cancer have remarkably decreased in all regions since 1990, countries with a lower SDI showed the highest rates in 2019, particularly in countries in Eastern Sub-Saharan Africa. Among all cancers, leukemia has shown the largest decrease in burden since 1990. Despite this, leukemia was still the most common cancer and the leading cause of death among children in 2019, followed by brain and central nervous system cancer. CONCLUSIONS: On a global scale, the childhood cancer burden has significantly fallen over the last 30 years, but is still higher in lower SDI countries. Effective interventions and collaborations among nations should be facilitated to improve healthcare among children with cancer in countries with lower SDI.

Global Burden of Respiratory Diseases Attributable to Ambient Particulate Matter Pollution: Findings From the Global Burden of Disease Study 2019.

Background: Exposure to ambient particulate matter pollution (APMP) is a global health issue that directly affects the human respiratory system. Thus, we estimated the spatiotemporal trends in the burden of APMP-related respiratory diseases from 1990 to 2019. Methods: Based on the Global Burden of Disease Study 2019, data on the burden of APMP-related respiratory diseases were analyzed by age, sex, cause, and location. Joinpoint regression analysis was used to analyze the temporal trends in the burden of different respiratory diseases over the 30 years. Results: Globally, in 2019, APMP contributed the most to chronic obstructive pulmonary disease (COPD), with 695.1 thousand deaths and 15.4 million disability-adjusted life years (DALYs); however, the corresponding age-standardized death and DALY rates declined from 1990 to 2019. Similarly, although age-standardized death and DALY rates since 1990 decreased by 24% and 40%, respectively, lower respiratory infections (LRIs) still had the second highest number of deaths and DALYs attributable to APMP. This was followed by tracheal, bronchus, and lung (TBL) cancer, which showed increased age-standardized death and DALY rates during the past 30 years and reached 3.78 deaths per 100,000 persons and 84.22 DALYs per 100,000 persons in 2019. Among children aged < 5 years, LRIs had a huge burden attributable to APMP, whereas for older people, COPD was the leading cause of death and DALYs attributable to APMP. The APMP-related burdens of LRIs and COPD were relatively higher among countries with low and low-middle socio-demographic index (SDI), while countries with high-middle SDI showed the highest burden of TBL cancer attributable to APMP. Conclusions: APMP contributed substantially to the global burden of respiratory diseases, posing a significant threat to human health. Effective actions aimed at air pollution can potentially avoid an increase in the PM2.5-associated disease burden, especially in highly polluted areas.

Global, Regional, and National Burden of Diabetes-Related Chronic Kidney Disease From 1990 to 2019.

Background: Chronic kidney disease (CKD) is a public health problem largely caused by diabetes. The epidemiology of diabetes mellitus-related CKD (CKD-DM) could provide specific support to lessen global, regional, and national CKD burden. Methods: Data were derived from the GBD 2019 study, including four measures and age-standardized rates (ASRs). Estimated annual percentage changes and 95% CIs were calculated to evaluate the variation trend of ASRs. Results: Diabetes caused the majority of new cases and patients with CKD in all regions. All ASRs for type 2 diabetes-related CKD increased over 30 years. Asia and Middle socio-demographic index (SDI) quintile always carried the heaviest burden of CKD-DM. Diabetes type 2 became the second leading cause of CKD and CKD-related death and the third leading cause of CKD-related DALYs in 2019. Type 2 diabetes-related CKD accounted for most of the CKD-DM disease burden. There were 2.62 million incident cases, 134.58 million patients, 405.99 thousand deaths, and 13.09 million disability-adjusted life-years (DALYs) of CKD-DM worldwide in 2019. Age-standardized incidence (ASIR) and prevalence rate (ASPR) of type 1 diabetes-related CKD increased, whereas age-standardized death rate (ASDR) and DALY rate decreased for females and increased for males. In high SDI quintile, ASIR and ASPR of type 1 diabetes-related CKD remained the highest, with the slowest increase, whereas the ASDR and age-standardized DALY rate remained the lowest there. In high SDI quintile, ASIR of type 2 diabetes-related CKD was the highest, with the lowest increasing rate. In addition, type 2 diabetes-related CKD occurred most in people aged 80-plus years worldwide. The main age of type 2 diabetes-related CKD patients was 55-64 years in Asia and Africa. The prevalence, mortality, and DALY rate of type 2 diabetes-related CKD increased with age. As for incidence, there was a peak at 80 years, and after age of 80, the incidence declined. CKD-DM-related anemia was mainly in mild to moderate grade. Conclusions: Increasing burden of CKD-DM varied among regions and countries. Prevention and treatment measures should be strengthened according to CKD-DM epidemiology, especially in middle SDI quintile and Asia.

Epidemiological trends of tracheal, bronchus, and lung cancer at the global, regional, and national levels: a population-based study.

BACKGROUND: Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. METHODS: We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990-2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. RESULTS: Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] - 0.03 to 0.08), but the age-standardized death (EAPC = - 0.34, 95%CI - 0.38 to - 0.3) and DALY rate decreased generally (EAPC = - 0.74, 95%CI - 0.8 to - 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were > 50 years, and the DALYs concentrated in 50 - 69 years. CONCLUSIONS: To significantly reduce the growing burden of TBL cancer, treatment resources need to be skewed according to factors such as risks and geography, especially for high-risk groups and high-burden areas. Asia had the greatest TBL cancer burden, followed by high-income North America. Tobacco remains the leading cause of death and DALYs, followed by air pollution. Effective prevention measures against tobacco and air pollution should be strengthened.

Global burden of larynx cancer, 1990-2017: estimates from the global burden of disease 2017 study.

Larynx cancer is one of the most common cancers in head and neck. This study aimed to investigate the health burden of larynx cancer at global, regional, and national levels. We collected data of larynx cancer between 1990 and 2017 from the Global Burden of Disease study, including incidence, mortality, and disability adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to assess the changes in age-standardized rate (ASR) of larynx cancer. From 1990 to 2017, LC incident cases increased by 58.67%; however, age-standardized incidence rate (ASIR) decreased, with an EAPC of -0.99. Additionally, the incident cases and ASIR of LC were 6-fold higher for male than those for female in 2017. Over the past 28 years, deaths and DALYs of larynx cancer increased by 33.84% and 25%. Contrarily, age-standardized death and DALY rate showed a downward trend. Incidence, death, and DALYs of larynx cancer were always the highest in people aged 50-69 years. Overall, all the ASRs showed downward trends globally. The majority of larynx cancer burden was observed in men, especially among male aged 50-69 years. South and East Asia carried the heaviest burden of larynx cancer worldwide.

Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the Global Burden of Disease Study 2017.

BACKGROUND: Statistical data on the incidence, mortality, and burden of breast cancer and the relevant risk factors are valuable for policy-making. We aimed to estimate breast cancer incidence, deaths, and disability-adjusted life years (DALYs) by country, gender, age group, and social-demographic status between 1990 and 2017. METHODS: We extracted breast cancer data from the 2017 Global Burden of Disease (GBD) study from 1990 through 2017 in 195 countries and territories. Data about the number of breast cancer incident cases, deaths, DALYs, and the age-standardized rates were collected. We also estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study. RESULTS: In 2017, the global incidence of breast cancer increased to 1,960,681 cases. The high social-development index (SDI) quintile included the highest number of breast cancer death cases. Between 2007 and 2017, the ASDR of breast cancer declined globally, especially in high SDI and high middle SDI countries. The related DALYs were 17,708,600 in 2017 with high middle SDI quintile as the highest contributor. Of the deaths and DALYs, alcohol use was the greatest contributor in most GBD regions and other contributors included high body mass index (BMI) and high fasting plasma glucose. CONCLUSION: The increasing global breast cancer burden is mainly observed in lower SDI countries; in higher SDI countries, the breast cancer burden tends to be relieving. Therefore, steps against attributable risk factors should be taken to reduce breast cancer burden in lower SDI countries.

Global, regional, and national burden of Hodgkin lymphoma from 1990 to 2017: estimates from the 2017 Global Burden of Disease study.

BACKGROUND: Hodgkin lymphoma (HL) is an uncommon B cell lymphoma. We assessed the global, regional, and national burden of HL from 1990 to 2017, by gender, age, and social-demographic index (SDI). METHODS: Data on HL, including incidence, mortality, and disability adjusted life-years (DALY), from 1990 to 2017 were obtained from the 2017 Global Burden of Disease study. Estimated annual percentage changes (EAPCs) were calculated to assess incidence rate, mortality, and DALY trends. RESULTS: HL incidences increased by 38.66%, from 72,937 in 1990 to 101,133 in 2017, while the age-standardized incidence rate (ASIR) was relatively stable. ASIR decreased in the low SDI regions (EAPC = - 2.58; 95% CI, from - 2.66 to - 2.49) and was stable in the other four SDI regions. Incidence showed a bimodal distribution with peak values in patients aged 20-39 years and patients aged 60 years or higher. The number of death cases and DALYs were stable. The age-standardized death rate decreased by 2.36% (95% CI, from - 2.43% to - 2.30%) per year. The annual age-standardized DALY rate decreased by 2.29% (95% CI, from - 2.36% to - 2.21%). The incidence and mortality in male subjects was higher than that in female subjects. The incidence in male and female subjects aged 15-30 years old was close, whereas the biggest difference existed in patients aged < 10 years old and 45-75 years old between genders. CONCLUSION: Globally, incidence of HL was stable, while mortality and DALY rate of HL had been decreasing from 1990 to 2017. Compared with lower and decreasing ASIR in the low SDI region, ASIR in the high SDI region was always high, indicating the need for HL treatment improvement and the establishment of more targeted and specific strategies in high SDI countries to reduce the incidence of HL.

CHA2DS2-VASc score as a predictor of long-term cardiac outcomes in elderly patients with or without atrial fibrillation.

BACKGROUND: The CHA2DS2-VASc score is often used for stroke risk stratification in atrial fibrillation (AF) patients. However, its usefulness in patients ≥75 years of age with or without AF is unclear. OBJECTIVE: We aimed to investigate whether the CHA2DS2-VASc score can predict ischemic stroke (IS), transient ischemic attack, thromboembolism (TE), and mortality in elderly patients with and without AF. MATERIALS AND METHODS: During 2013-2014, 1,071 patients (36.3% with concomitant AF) at least 75 years old were enrolled, and the follow-up ended on July 15, 2017. Variables included sociodemographic characteristics, complications, drugs taken, laboratory results, and echocardiographic parameters. The primary end points were IS, transient ischemic attack, and TE, expressed as IS/TE. All-cause mortality was a secondary end point. Survival curves and mortality risks were assessed via Kaplan-Meier survival analysis and compared by log-rank tests. RESULTS: The average follow-up duration was 2.57±1.37 years. Overall, 167 patients (5.6%) died and 77 (7.2%) developed IS/TE. The CHA2DS2-VASc score was associated with IS/TE in patients 75 years or older with and without AF, and patients with a CHA2DS2-VASc score ≥5 had a higher risk of stroke. However, the CHA2DS2-VASc score was not related to all-cause mortality. CONCLUSION: The CHA2DS2-VASc score can predict IS/TE, but not mortality, in elderly patients (≥75 years) with or without AF.

Functional and anatomical connectivity abnormalities in cognitive division of anterior cingulate cortex in schizophrenia.

INTRODUCTION: Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI). METHODS: Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively. RESULTS: Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (p=0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients. CONCLUSIONS: Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.

The clinical value of serum connective tissue growth factor in the assessment of liver fibrosis.

To explore the relation between connective tissue growth factor (CTGF) in serum and the severity of liver fibrosis, and to determine the clinical value of CTGF in the assessment of liver fibrosis, serum CTGF was tested utilizing enzyme-linked immunosorbent assay (ELISA). The correlation between serum CTGF concentration and fibrosis stage was assessed. The diagnostic performance of CTGF was assessed by comparing the area under the receiver operating characteristic (ROC) curves (AUC) with a panel of fibrosis markers. The correlation coefficient was 0.689 (P < 0.001) between the levels of serum CTGF and fibrosis stages and the AUC of CTGF was 0.841 (95% confidence interval [CI] 0.762-0.920) in distinguishing mild fibrosis from significant fibrosis. The present data revealed that serum CTGF was significantly correlated with the stage of liver fibrosis, suggested that serum CTGF was an indicator for the stage of liver fibrosis, and shown evidence that serum CTGF could be used as a valuable marker for assessing liver fibrosis.

An entropy-based approach for testing genetic epistasis underlying complex diseases.

The genetic basis of complex diseases is expected to be highly heterogeneous, with complex interactions among multiple disease loci and environment factors. Due to the multi-dimensional property of interactions among large number of genetic loci, efficient statistical approach has not been well developed to handle the high-order epistatic complexity. In this article, we introduce a new approach for testing genetic epistasis in multiple loci using an entropy-based statistic for a case-only design. The entropy-based statistic asymptotically follows a chi(2) distribution. Computer simulations show that the entropy-based approach has better control of type I error and higher power compared to the standard chi(2) test. Motivated by a schizophrenia data set, we propose a method for measuring and testing the relative entropy of a clinical phenotype, through which one can test the contribution or interaction of multiple disease loci to a clinical phenotype. A sequential forward selection procedure is proposed to construct a genetic interaction network which is illustrated through a tree-based diagram. The network information clearly shows the relative importance of a set of genetic loci on a clinical phenotype. To show the utility of the new entropy-based approach, it is applied to analyze two real data sets, a schizophrenia data set and a published malaria data set. Our approach provides a fast and testable framework for genetic epistasis study in a case-only design.