9064 Background: Immunotherapy has unequal efficacies in populations with different clinical or histological features. This study aims to explore inter-subgroup differences in responses to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and find the optimal treatments for each subgroup. Methods: We performed (network) meta-analyses of phase III random controlled trials, in which efficacies of 10 immunotherapy-based treatments were compared, including anti-programmed death receptor-1 (PD-1) (+chemotherapy), anti-programmed death ligand-1 (PD-L1) (+chemotherapy), anti-PD-L1+anti-cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-PD-1+anti-CTLA-4 (+chemotherapy), anti-CTLA-4+chemotherapy, anti-PD-1+anti-angiogenic therapy (AT)+chemotherapy, and anti-PD-L1+AT+chemotherapy, for 19 subgroups by sex, age, smoking status, metastatic site (liver/brain/bone), histological type (squamous/non-squamous cancer), and PD-L1 expression, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and their 95% confidence intervals (CIs). Results: 22 studies comprised of 12678 patients with advanced NSCLC were included in our study. The results showed OS and PFS advantages of immunotherapy-based treatments in 16 out of 19 subgroups comparing with chemotherapy. Never-smokers (OS-HR 0.81, 95% CI 0.55-1.18; PFS-HR 0.73, 95% CI 0.51-1.07), ¡Ý75-year-old patients (OS-HR 0.9, 95% CI 0.71-1.13), and patients with liver metastases (OS-HR 0.88, 95% CI 0.77-1) showed indisposed responses to immunotherapy. In patients with PD-L1 tumor proportion score (TPS)<1%, anti-CTLA-4+anti-PD-1 and anti-PD-1+anti-CTLA-4+chemotherapy had significant OS benefit comparing with anti-PD-L1 monotherapy (HR 0.6, 95% CI 0.44-0.81; HR 0.6, 95% CI 0.41-0.87; respectively) and anti-PD-L1+AT+chemotherapy (HR 0.66, 95% CI 0.48-0.92; HR 0.66, 95% CI 0.45-0.98; respectively). In patients with liver metastases, anti-PD-L1+AT+chemotherapy showed significant PFS advantage comparing with anti-PD-L1+chemotherapy (HR 0.51, 95% CI 0.33-0.77). As for other populations, anti-PD-1+chemotherapy showed wide-ranging promising efficacies in multiple subgroups. Conclusions: Patients with advanced NSCLC generally benefit from immunotherapy. Specific immunotherapy treatments should be applied according to different clinical or histological features. Meanwhile, we expect more preclinical and clinical studies to focus on therapeutic strategies for populations with impaired responses towards immunotherapy. Funding: CSCO-BMS Oncologic Research Foundation (Grant No. Y-BMS2019-100); Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120) and Guangdong Association of Clinical Trials (GACT); Changsha Science and Technology Bureau (Grant No. kq1907077).
Abstract Background Immunotherapy has unequal efficacies in different populations. This study aims to explore inter-subgroup differences in responses to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and find the optimal treatments for each subgroup. Methods We performed (network) meta-analyses of phase III random controlled trials, in which efficacies of 10 immunotherapy-based treatments were compared with each other and chemotherapy, including anti-programmed death receptor-1 (PD-1) (+chemotherapy), anti-programmed death ligand-1 (PD-L1) (+chemotherapy), anti-PD-L1+anti-cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-PD-1+anti-CTLA-4 (+chemotherapy), anti-CTLA-4+chemotherapy, anti-PD-1+anti-angiogenic therapy (AT)+chemotherapy, and anti-PD-L1+AT+chemotherapy, for 19 subgroups by sex, age, smoking status, metastatic site, histological type, and PD-L1 expression, using subgroup-level hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and their 95% confidence intervals (CIs). Results 22 studies comprised of 12678 patients were included in our analyses. The results showed survival advantages of immunotherapy-based treatments in 16 out of 19 subgroups comparing with chemotherapy. In patients with PD-L1 tumor proportion score (TPS)<1%, anti-CTLA-4+anti-PD-1 and anti-PD-1+anti-CTLA-4+chemotherapy had OS benefits comparing with anti-PD-L1 monotherapy (HR 0.6, 95% CI 0.44-0.81; HR 0.6, 95% CI 0.41-0.87; respectively) and anti-PD-L1+AT+chemotherapy (HR 0.66, 95% CI 0.48-0.92; HR 0.66, 95% CI 0.45-0.98; respectively). In patients with liver metastases, anti-PD-L1+AT+chemotherapy showed PFS advantage comparing with anti-PD-L1+chemotherapy (HR 0.51, 95% CI 0.33-0.77). As for other populations, anti-PD-1+chemotherapy showed promising efficacies in multiple subgroups. Conclusions Patients with advanced NSCLC generally benefit from immunotherapy. Specific immunotherapy treatments should be applied according to different clinical or histological features. Meanwhile, we expect more studies to investigate treatments for populations with impaired responses towards immunotherapy.
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma. In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.
Methods
Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex. Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases. We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.
Findings
In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9–584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990. Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia. The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically. Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8–7·2] of all deaths), behind cardiovascular diseases and neoplasms. Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578–4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%. However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%). In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD. In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes. Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world. Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions. Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men. Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.
Interpretation
Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990. Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.
There are persistent disparities in stomach cancer mortality among racial-ethnic groups in the USA, but the extent to which these patterns vary geographically is not well understood. This analysis estimated age-standardised mortality for five racial-ethnic groups, in 3110 USA counties over 20 years, to describe spatial-temporal variations in stomach cancer mortality and disparities between racial-ethnic groups.Redistribution methods for insufficient cause of death codes and validated small area estimation methods were applied to death registration data from the US National Vital Statistics System and population data from the US National Center for Health Statistics to estimate annual stomach cancer mortality rates. Estimates were stratified by county and racial-ethnic group (non-Latino and non-Hispanic [NL] American Indian or Alaska Native [AIAN], NL Asian or Pacific Islander [Asian], NL Black [Black], Latino or Hispanic [Latino], and NL White [White]) from 2000 to 2019. Estimates were corrected for misreporting of racial-ethnic group on death certificates using published misclassification ratios. We masked (ie, did not display) estimates for county and racial-ethnic group combinations with a mean annual population of less than 1000; thus, we report estimates for 3079 (of 3110) counties for the total population, and 474, 667, 1488, 1478, and 3051 counties for the AIAN, Asian, Black, Latino, and White populations, respectively.Between 2000 and 2019, national age-standardised stomach cancer mortality was lowest among the White population in every year. Nationally, stomach cancer mortality declined for all racial-ethnic groups across this time period, with the most rapid declines occurring among the Asian (percent decline 48.3% [45.1-51.1]) and Black populations (42.6% [40.2-44.6]). Mortality among the other racial-ethnic groups declined more moderately, decreasing by 36.7% (35.3-38.1), 35.1% (32.2-37.7), and 31.6% (23.9-38.0) among the White, Latino, and AIAN populations, respectively. Similar patterns were observed at the county level, although with wide geographic variation. In 2019, a majority of counties had higher mortality rates among minoritised racial-ethnic populations compared to the White population: 81.1% (377 of 465 counties with unmasked estimates for both racial-ethnic groups) among the AIAN population, 88.2% (1295 of 1469) among the Latino population, 99.4% (663 of 667) among the Asian population, and 99.9% (1484 of 1486) among the Black population. However, the size of these disparities ranged widely across counties, with the largest range from 0.3 to 17.1 among the AIAN population.Stomach cancer mortality has decreased substantially across populations and geographies in the USA. However, disparities in stomach cancer mortality among racial-ethnic groups are widespread and have persisted over the last two decades. Local-level data are crucial to understanding the scope of this unequal burden among minoritised groups in the USA.National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Sciences Research, National Institutes of Health (contract #75N94019C00016).
We consider statistical inference problems under uncertain equality constraints, and provide asymptotically valid uncertainty estimates for inferred parameters. The proposed approach leverages the implicit function theorem and primal-dual optimality conditions for a particular problem class. The motivating application is multi-dimensional raking, where observations are adjusted to match marginals; for example, adjusting estimated deaths across race, county, and cause in order to match state all-race all-cause totals. We review raking from a convex optimization perspective, providing explicit primal-dual formulations, algorithms, and optimality conditions for a wide array of raking applications, which are then leveraged to obtain the uncertainty estimates. Empirical results show that the approach obtains, at the cost of a single solve, nearly the same uncertainty estimates as computationally intensive Monte Carlo techniques that pass thousands of observed and of marginal draws through the entire raking process.
<p dir="ltr">Objective</p><p dir="ltr">Diabetes is a leading cause of death in the USA. Previous studies have found substantial racial and ethnic and geographical disparities in diabetes mortality, however research considering racial and ethnic and geographical disparities simultaneously has been limited. To fill this gap, we estimated trends in diabetes mortality rates from 2000 to 2019 at the county level for five racial and ethnic populations. </p><p><br></p><p dir="ltr">Research Design and Methods</p><p dir="ltr">We applied small-area estimation methods to death registration data from the US National Vital Statistics System and population data from the US National Center for Health Statistics and corrected for misclassification of race and ethnicity on death certificates. </p><p><br></p><p dir="ltr">Results</p><p dir="ltr">Age-standardized diabetes mortality rates decreased in the USA from 28.1 (95% uncertainty interval 27.9–28.2) in 2000 to 19.1 (19.0–19.2) deaths per 100,000 population in 2019. In 2019, national-level rates were highest for the AIAN population (35.6 [32.1–39.4]), followed by the Black (31.9 [31.5–32.3]), Latino (19.7 [19.3–20.2]), White (17.6 [17.5–17.8]), and Asian (12.6 [12.1–13.1]) populations. There was substantial heterogeneity in diabetes mortality rates across counties within each racial and ethnic population, with the AIAN population experiencing the greatest heterogeneity in 2019 (IQR 18.7–50.3 [median 31.9]). For each racial and ethnic population, mortality rates declined in most counties from 2000–2019.</p><p dir="ltr">Conclusions</p><p dir="ltr">Since 2000, progress has been made in reducing diabetes mortality rates. Nonetheless, diabetes mortality remains too high for many Americans. Interventions focusing on communities at highest risk are vital to resolving persistent health inequities.</p><p><br></p>
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