In-depth analysis and trends of cancer mortality in Kazakhstan: a joinpoint analysis of nationwide healthcare data 2014-2022.

BACKGROUND: Cancer remains a leading cause of death both globally and in Kazakhstan, making it crucial to track its mortality trends. This study aimed to investigate cancer mortality trends from 2014 to 2022 in Kazakhstan. METHODS: This study utilized data from Kazakhstan's Unified National Electronic Health System to perform descriptive data analysis and employed Joinpoint regression models to analyze average annual percent change (AAPC) in cancer-related mortality estimates. The authors also examined the mortality-to-incidence ratio (MIR) and proportionate mortality (PM). RESULTS: The study analyzed 123,622 cancer-related death reports from 2014 to 2022. Major causes included trachea, bronchus, and lung cancer (16.01%), stomach cancer (11.43%), and colon and rectum cancer (10.05%), accounting for 37.48% of all cancer-related deaths. AAPCs showed a significant increase in mortality for individuals aged 18-44 (1.36%; 95% CI: 0.05%; 2.71%), while those aged 45-59 and 60-74 experienced decreases of -2.02% (95% CI: -3.05%; -0.96%) and - 2.10% (95% CI:-3.22%; -0.96%), respectively. PM was stable until 2019 but decreased from 2020 to 2021, while MIR increased during the same period. A significant decrease in oesophageal cancer mortality was observed in both females (-4.03%; 95% CI: -6.11%; -1.83%) and males (-2.44%; 95% CI: -4.89%; -0.02%), whereas ovarian cancer mortality increased by 0.95% (95% CI: 0.03%; 1.91%). In males, mortality from trachea, bronchus, and lung cancers decreased by -2.14% (95% CI: -3.00%; -1.25%), while "other neoplasms" rose by 6.21% (95% CI: 1.40%; 11.27%). Regional analysis highlighted variability, with the Kyzylorda region showing a pronounced increase in mortality (27.18%; 95% CI: 14.11%; 42.35%). CONCLUSIONS: Despite slight increases in MIR during the COVID-19 pandemic, overall cancer mortality trends remained stable. The findings highlight the need for targeted interventions, especially for individuals aged 18-44, ovarian cancer, and "other neoplasms". Further research is needed to explore regional mortality variations.

Temporal trends, spatial and spatiotemporal clusters of cervical cancer mortality in Brazil from 2000 to 2021.

Cervical cancer, despite being preventable through primary and secondary prevention strategies, remains one of the leading causes of morbidity and mortality among women in Brazil. This study aimed to analyze the temporal, spatial, and space-time patterns of cervical cancer mortality in Brazil. An ecological study was conducted using temporal, spatial, and space-time analysis techniques, using death certificates with cervical cancer as the underlying cause or associated condition among females in Brazil from 2000 to 2021. Death certificate and population data were provided by the Department of Health Informatics of the Unified Health System (DATASUS) and the Brazilian Institute of Geography and Statistics (IBGE), respectively. A total of 123,306 deaths associated with cervical cancer among women were registered during the study period. A rising trend in mortality was detected since 2014 onwards, after 14 years of decline. Particularly, an increase in mortality was observed among the younger age groups, and in the North and Northeast regions regardless of age. Heterogeneity in the spatial distribution of cervical cancer mortality was observed, with high mortality clusters around the country, but mostly concentrated in the North and Northeast regions. These findings suggest a need and an opportunity to develop efficient and effective health policies targeting those regions and groups of women at higher risk which in turn will allow for fast and significant reductions in cervical cancer mortality in Brazil.

Faltering mortality improvements at young-middle ages in high-income English-speaking countries.

BACKGROUND: Before the COVID-19 pandemic, stagnating life expectancy trends were reported in some high-income countries (HICs). Despite previous evidence from country-specific studies, there is a lack of comparative research that provides a broader perspective and challenges existing assumptions. This study aims to examine longevity trends and patterns in six English-speaking countries (Australia, Canada, Ireland, New Zealand, United Kingdom, United States) by combining period and cohort perspectives and to compare them with other HICs. METHODS: Using data from the Human Mortality and World Health Organization Mortality Databases, we estimated partial life expectancy, lifespan inequality and cohort survival differences for 1970-2021, as well as the contribution of causes of death to the gap in life expectancy between English-speaking countries and the average for other HICs in 2017-19. RESULTS: In the pre-pandemic period, the increase in life expectancy slowed in all English-speaking countries, except Ireland, mainly due to stagnating or rising mortality at young-middle ages. Relative to other HICs, those born in Anglophone countries since the 1970s experienced relative survival disadvantage, largely attributable to injuries (mainly suicides) and substance-related mortality (mainly poisonings). In contrast, older cohorts enjoyed advantages for females in Australia and Canada and for males in all English-speaking countries except the United States. CONCLUSIONS: Although future gains in life expectancy in wealthy societies will increasingly depend on reducing mortality at older ages, adverse health trends at younger ages are a cause for concern. This emerging and avoidable threat to health equity in English-speaking countries should be the focus of further research and policy action.

Unbiased temperature-related mortality estimates using weekly and monthly health data: a new method for environmental epidemiology and climate impact studies.

BACKGROUND: Exposure to environmental factors has a high burden on human health, with millions of premature annual deaths associated with the short-term health effects of ambient temperatures and air pollution. However, direct estimations of exposure-related mortality from real data are still not available in most parts of the world, especially in low-resource settings, due to the unavailability of daily health records to calibrate epidemiological models. METHODS: In this study, we have filled the crucial gap in available direct estimations by developing a method to make valid inference for the relationship between exposure and response data that uses only exposure and temporally aggregated response data. We provided the mathematical derivation of the method, and compared the results by using simulations applied to daily temperature and daily, weekly, and monthly mortality data. The method was then applied to the newly created database of the EARLY-ADAPT project. FINDINGS: The daily and weekly models produced similar and unbiased estimates of the temperature-related relative risks and attributable mortality, with only slightly more imprecision in the weekly model. Even the estimates of the monthly model were unbiased when using enough data, although at the expense of a substantial increase in variability. The real data analysis showed that the similarity between the regional values of two aggregation models increased with the number of years and regions of the dataset, and decreased with the difference in their degree of temporal aggregation. INTERPRETATION: Our method opens the door to conducting epidemiological studies in low-resource settings, where access to daily health data is not possible. Moreover, it allows accurate estimation of the short-term health effects of environmental exposures in near-real time, when daily health data are still not available, such as in the estimation of the mortality burden of recent record-breaking heat episodes. Overall, our method represents an important new approach to how the public health community can use data to create new evidence for research, translation and policy making. FUNDING: European Research Council (ERC).

Projecting future excess deaths associated with extreme precipitation events in China under changing climate: an integrated modelling study.

BACKGROUND: Climate-change-induced extreme precipitation events have attracted global attention; however, the associated excess deaths burden has been insufficiently explored and remains unclear. METHODS: We first defined an extreme precipitation event for each county when the daily total precipitation exceeded the county-specific 99·5th percentile of the daily precipitation from 1986 to 2005; then we estimated the associations between extreme precipitation events and cause-specific deaths in 280 Chinese counties using a two-stage time-series model. Second, we projected the excess deaths related to extreme precipitation events by combining the bias-corrected multi-model precipitation predictions derived under different combined emission-population scenarios of three representative concentration pathways (RCPs; RCP2·6, RCP4·5, and RCP8·5) and three shared socioeconomic pathways (SSP2, a business-as-usual scenario) populations (S1, low fertility rate; S2, medium fertility rate; and S3, high fertility rate). We quantified the climate and population contributions to the changes of future excess deaths nationwide and by climatic zones. FINDINGS: Compared with the non-extreme precipitation days, the percentage increase of deaths associated with exposure to extreme precipitation days is 13·0% (95% CI 7·0-19·3) for accidental cause, 4·3% (2·0-6·6) for circulatory disease, and 6·8% (2·8-10·9) for respiratory disease. The number of annual average excess deaths related to extreme precipitation events during 1986-2005 was 2644 (95% CI 1496-3730) for accidental cause, 69 (33-105) for circulatory disease, and 181 (79-279) for respiratory disease. In the 2030s, the total number of excess deaths of these three causes will increase by 1244 (43%), 1756 (61%), and 2008 (69%) under RCP2·6, RCP4·5, and RCP8·5 scenarios combined with a medium-fertility-rate population (SSP2-S2), respectively, but will decrease by 3% under RCP2·6-SSP2-S2 and increase by 25% under RCP8·5-SSP2-S2 in the 2090s. Humid and water-limited regions in subtropical, middle-temperate, and plateau climate zones will face highly increased risks. Climate and population factors contributed disproportionally among the five climate zones. INTERPRETATION: This study is the largest integrated projection exploring the disease burden associated with extreme precipitation events. The excess deaths will be amplified by climate and population changes. Improving mitigation and adaptation capacities is crucial when responding to precipitation extremes. FUNDING: National Natural Science Foundation of China and Wellcome Trust.

Tree-based analysis of longevity predictors and their ten-year changes: a 35-Year mortality follow-up.

BACKGROUND: Prior studies on longevity often examine predictors in isolation and rely solely on baseline information, limiting our understanding of the most important predictors and their dynamic nature. In this study, we used an innovative regression tree model to explore the common characteristics of those who lived longer than their age and sex peers in 35-years follow-up. We identified different pathways leading to a long life, and examined to how changes in characteristics over 10 years (from 1979 to 1989) affect the findings on longevity predictors. METHODS: Data was obtained from the "Tampere Longitudinal Study on Ageing" (TamELSA) in Finland. Survey data was collected in 1979 from 1056 participants aged 60-89 years (49.8% men). In 1989, a second survey was conducted among 432 survivors from the 1979 cohort (40.2% men). Dates of death were provided by the Finnish Population Register until 2015. We employed an individual measure of longevity known as the realized probability of dying (RPD), which was calculated based on each participant's age and sex, utilizing population life tables. RPD is based on a comparison of the survival time of each individual of a specific age and sex with the survival time of his/her peers in the total population. A regression tree analysis was used to examine individual-based longevity with RPD as an outcome. RESULTS: This relative measure of longevity (RPD) provided a complex regression tree where the most important characteristics were self-rated health, years of education, history of smoking, and functional ability. We identified several pathways leading to a long life such as individuals with (1) good self-rated health (SRH), short smoking history, and higher education, (2) good SRH, short smoking history, lower education, and excellent mobility, and (3) poor SRH but able to perform less demanding functions, aged 75 or older, willing to do things, and sleeping difficulties. Changes in the characteristics over time did not change the main results. CONCLUSION: The simultaneous examination of a broad range of potential predictors revealed that longevity can be achieved under very different conditions and is achieved by heterogeneous groups of people.

Excess Deaths in Korea During the COVID-19 Pandemic: 2020-2022.

OBJECTIVES: Excess deaths, an indicator that compares total mortality rates before and during a pandemic, offer a comprehensive view of the pandemic's impact. However, discrepancies may arise from variations in estimating expected deaths. This study aims to compare excess deaths in Korea during the coronavirus disease 2019 pandemic using 3 methods and to analyze patterns using the most appropriate method. METHODS: Expected deaths from 2020 to 2022 were estimated using mortality data from 2015-2019 as reference years. This estimation employed 3 approaches: (1) simple average, (2) age-adjusted average, and (3) age-adjusted linear regression. Excess deaths by age, gender, and cause of death were also presented. RESULTS: The number of excess deaths varied depending on the estimation method used, reaching its highest point with the simple average and its lowest with the age-adjusted average. Age-adjusted linear regression, which accounts for both the aging population and declining mortality rates, was considered most appropriate. Using this model, excess deaths were estimated at 0.3% for 2020, 4.0% for 2021, and 20.7% for 2022. Excess deaths surged among individuals in their 20s throughout the pandemic, largely attributed to a rise in self-harm and suicide. Additionally, the results indicated sharp increases in deaths associated with "endocrine, nutritional, and metabolic diseases" and "symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified." CONCLUSIONS: Substantial variations in excess deaths were evident based on estimation method, with a notable increase in 2022. The heightened excess deaths among young adults and specific causes underscore key considerations for future pandemic responses.

Association of fish intake with all-cause mortality according to CRP levels or inflammation in older adults: a prospective cohort study.

BACKGROUND: The relationship between inflammatory response, fish consumption, and mortality risk in older individuals is unclear. We investigated whether C-reactive protein (CRP) levels ≥ 0.1 mg/dL, fish intake, and inflammatory responses are associated with all-cause mortality risk in older adults. METHODS: This prospective cohort study included older adults aged 85-89 years from the Kawasaki Aging and Wellbeing Project, who did not require daily care. Cohort was recruited from March 2017 to December 2018 (follow-up ended on December 31, 2021). Dietary assessment was conducted using the Brief Self-Administered Diet History Questionnaire. Multivariate Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality in the CRP ≥ 0.1 mg/dL group; the CRP < 0.1 mg/dL group was used for reference. Within CRP ≥ 0.1 and < 0.1 mg/dL groups, participants were categorized into tertiles of fish intake. HRs and 95% CIs for all-cause mortality in the other groups were estimated using the lower tertile group as a reference. RESULTS: The study included 996 participants (mean [standard deviation] age, 86.5 [1.37] years; 497 [49.9%] women) with a median CRP level of 0.08 (interquartile range [IQR] = 0.04-0.16). There were 162 deaths during 4,161 person-years of observation; the multivariable-adjusted HR for all-cause mortality in the CRP ≥ 0.1 mg/dL group was 1.86 (95% CI, 1.32-2.62); P < 0.001. In 577 individuals with median (IQR) fish intake of 39.3 g/1000 kcal (23.6-57.6) and CRP level of < 0.1 mg/dL, the multivariable-adjusted HR for all-cause mortality in the higher tertile group of fish intake was 1.15 (0.67-1.97); P = 0.59, non-linear P = 0.84. In 419 individuals with median (IQR) fish intake of 40.7 g/1000 kcal (25.0-60.1) and CRP level of ≥ 0.1 mg/dL, the multivariate-adjusted HR for all-cause mortality in the higher tertile group of fish intake was 0.49 (0.26-0.92); P = 0.026, non-linear P = 0.38, P-value for interaction = 0.040. CONCLUSIONS: A negative association between fish intake and all-cause mortality was seen in older adults with elevated CRP levels, which is a mortality risk factor. While the results may be limited owing to stringent methods ensuring impartiality, they offer valuable insights for future research. TRIAL REGISTRATION: UMIN000026053. Registered February 24, 2017.

Association of oxidative balance score with all-cause mortality among individuals with chronic kidney disease: a cohort study.

BACKGROUND: The Oxidative Balance Score (OBS) is employed for evaluating the body's overall level of oxidative stress. This study aimed to investigate the association between OBS and mortality in individuals with chronic kidney disease (CKD) using a cohort study design. METHODS: We used data from adult participants(≥ 20 years old) in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. CKD is diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. OBS, which consists of 16 dietary factors and 4 lifestyle factors, categorized into pro-oxidants and antioxidants, with a total score range of 0 to 40 .The OBS was divided into four quartiles (Q1 to Q4), with Q1 (5-12), Q2 (13-18), Q3 (19-24), and Q4 (25-36). We excluded patients with missing data on OBS, CKD, and key covariates.Cox regression analysis were used to examine the relationship between OBS and all-cause mortality in CKD patients. Sensitivity analyses included subgroup analysis and multiple imputation. RESULTS: We included a total of 3,984 patients with CKD. During an average follow-up period of 103 months, 1,263 cases (31.7%) of all-cause mortality were recorded. In the fully adjusted model, compared to Q1 the hazard ratios (HRs) and 95% confidence intervals (CIs) for Q4 were as follows: OBS 0.80 (0.68, 0.95) (p = 0.012), dietary OBS 0.78 (0.66, 0.92) (p = 0.003), and lifestyle OBS 0.83 (0.70, 0.99) (p = 0.038). Our sensitivity analyses further confirmed the robustness of these results. CONCLUSIONS: Higher OBS was negatively correlated with all-cause mortality risk in American adults with CKD.

Saturation association between serum 25-hydroxyvitamin D levels and mortality in elderly people with hyperlipidemia: a population-based study from the NHANES (2001-2016).

Background: 25-hydroxyvitamin D is the body's main storage form of vitamin D and is internationally recognized as the best indicator of vitamin D status in the human body. There is a scarcity of research investigating the interrelationship between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality among elderly individuals with hyperlipidemia. To address this knowledge gap, we examined the association between serum 25(OH)D levels and mortality in an older hyperlipidemic population from NHANES, while controlling for other influential factors. The study sought to elucidate the correlation between serum 25(OH)D levels and mortality about all-cause mortality, cardiovascular disease (CVD), malignant neoplasms, and mortality from other causes. Methods: The data from NHANES 2001-2016, including 9,271 participants were analyzed to examine the association between serum 25(OH)D levels and mortality. The interrelationship was illustrated using Kaplan-Meier curves and restricted cubic splines, while the Cox proportional hazards model was utilized to estimate the multifactor adjusted hazard ratio (HR). Results: This study included 9,271 participants (43.28% male) with an average age of 69.58 years, and the average duration of participant follow-up was 88.37 months. Kaplan-Meier curves demonstrated that lower serum 25(OH)D levels were associated with increased risks of all-cause mortality, cardiovascular mortality, malignant neoplasm mortality, and mortality from other causes. This negative association was further confirmed by the Cox proportional hazards models. Additionally, restricted cubic splines not only revealed this negative association but also highlighted the saturated serum 25(OH)D levels. Moreover, subgroup analyses indicated that the inverse correlation between serum 25(OH)D levels and all-cause mortality was more pronounced in the non-obese and smoking population. And the inverse correlation with mortality from other causes was even stronger in the non-obese population. Conclusions: In the elderly population with hyperlipidemia, 25(OH)D serum levels were negatively correlated with both cause-specific mortality and all-cause mortality. Moreover, there was a threshold effect in this negative association.

Long-term exposure to PM2.5 and mortality: a national health insurance cohort study.

BACKGROUND: Previous studies with large data have been widely reported that exposure to fine particulate matter (PM2.5) is associated with all-cause mortality; however, most of these studies adopted ecological time-series designs or have included limited study areas or individuals residing in well-monitored urban areas. However, nationwide cohort studies including cause-specific mortalities with different age groups were sparse. Therefore, this study examined the association between PM2.5 and cause-specific mortality in South Korea using the nationwide cohort. METHODS: A longitudinal cohort with 187 917 National Health Insurance Service-National Sample Cohort participants aged 50-79 years in enrolment between 2002 and 2019 was used. Annual average PM2.5 was collected from a machine learning-based ensemble model (a test R2 = 0.87) as an exposure. We performed a time-varying Cox regression model to examine the association between long-term PM2.5 exposure and mortality. To reduce the potential estimation bias, we adopted generalized propensity score weighting method. RESULTS: The association with long-term PM2.5 (2-year moving average) was prominent in mortalities related to diabetes mellitus [hazard ratio (HR): 1.03 (95% CI: 1.01, 1.06)], circulatory diseases [HR: 1.02 (95% CI: 1.00, 1.03)] and cancer [HR: 1.01 (95% CI: 1.00, 1.02)]. Meanwhile, circulatory-related mortalities were associated with a longer PM2.5 exposure period (1 or 2-year lags), whereas respiratory-related mortalities were associated with current-year PM2.5 exposure. In addition, the association with PM2.5 was more evident in people aged 50-64 years than in people aged 65-79 years, especially in heart failure-related deaths. CONCLUSIONS: This study identified the hypothesis that long-term exposure to PM2.5 is associated with mortality, and the association might be different by causes of death. Our result highlights a novel vulnerable population: the middle-aged population with risk factors related to heart failure.

Unraveling the impact of the COVID-19 pandemic on the mortality trends in Belgium between 2020-2022.

BACKGROUND: Over the past four years, the COVID-19 pandemic has exerted a profound impact on public health, including on mortality trends. This study investigates mortality patterns in Belgium by examining all-cause mortality, excess mortality, and cause-specific mortality. METHODS: We retrieved all-cause mortality data from January 1, 2009, to December 31, 2022, stratified by age group and sex. A linear mixed model, informed by all-cause mortality from 2009 to 2019, was used to predict non-pandemic all-cause mortality rates in 2020-2022 and estimate excess mortality. Further, we also analyzed trends in cause-specific and premature mortality. RESULTS: Different all-cause mortality patterns could be observed between the younger (<45 years) and older age groups. The impact of the COVID-19 pandemic was particularly evident among older age groups. The highest excess mortality occurred in 2020, while a reversal in this trend was evident in 2022. We observed a notable effect of COVID-19 on cause-specific and premature mortality patterns over the three-year period. CONCLUSIONS: Despite a consistent decline in COVID-19 reported mortality over this three-year period, it remains imperative to meticulously monitor mortality trends in the years ahead.

The impact of changing exposure to PM2.5 on mortality for US diplomats with multiple international relocations: a modelling study.

BACKGROUND: Current evidence linking long-term exposure to fine particulate matter (PM2.5) exposure and mortality is primarily based on persons that live in the same residence, city and/or country throughout the study, with few residential moves or relocations. We propose a novel method to quantify the health impacts of PM2.5 for United States (US) diplomats who regularly relocate to international cities with different PM2.5 levels. METHODS: Life table methods were applied at an individual-level to US mortality statistics using the World Health Organization's database of city-specific PM2.5 annual mean concentrations. Global Burden of Disease concentration-response (C-R) functions were used to estimate cause-specific mortality and days of life lost (DLL) for a range of illustrative 20-year diplomatic assignments for three age groups. Time lags between exposure and exposure-related mortality risks were applied. Sensitivity analysis of baseline mortality, exposure level, C-R functions and lags was conducted. The effect of mitigation measures, including the addition of air purifiers, was examined. RESULTS: DLL due to PM2.5 exposure for a standard 20-year assignment ranged from 0.3 days for diplomats' children to 84.1 days for older diplomats. DLL decreased when assignments in high PM2.5 cities were followed by assignments in low PM2.5 cities: 162.5 DLL when spending 20 years in high PM2.5 cities compared to 62.6 DLL when spending one of every four years (5 years total) in a high PM2.5 city for older male diplomats. Use of air purifiers and improved home tightness in polluted cities may halve DLL due to PM2.5 exposure. The results were highly sensitive to lag assumptions: DLL increased by 68% without inception lags and decreased by 59% without cessation lags for older male diplomats. CONCLUSION: We developed a model to quantify health impacts of changing PM2.5 exposure for a population with frequent relocations. Our model suggests that alternating assignments in high and low PM2.5 cities may help reduce PM2.5-related mortality burdens. Adding exposure mitigation at home may help reduce PM2.5 related mortality. Further research on outcome-specific lag structures is needed to improve the model.

Reproduction has immediate effects on female mortality, but no discernible lasting physiological impacts: A test of the disposable soma theory.

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and over lifetime. We found that reproduction had an immediate and negative effect on survival due to problems encountered during parturition for some females. However, there was no statistically significant residual effect on survival once breeding had ceased, indicating no trade-off with somatic maintenance. Instead, higher mortality appeared to be a direct consequence of reproduction without long-term physiological consequences. Reproduction did not elevate oxidative stress. Our findings do not provide support for the predictions of the DST.

Long-Term Exposure to Outdoor Ultrafine Particles and Black Carbon and Effects on Mortality in Montreal and Toronto, Canada.

INTRODUCTION: Numerous studies support an important relationship between long-term exposure to outdoor fine particulate air pollution (PM2.5) and both nonaccidental and cause-specific mortality. Less is known about the long-term health consequences of other traffic pollutants, including ultrafine particles (UFPs, <0.1 µm) and black carbon (BC), which are often present at elevated concentrations in urban areas but are not currently regulated. Knowledge is lacking largely because these pollutants generally are not monitored by governments and vary greatly over small spatial scales, hindering the evaluation of long-term exposures in population-based studies. METHODS: We aimed to estimate associations between long-term exposures to outdoor UFPs and BC and nonaccidental and cause-specific mortality in Canada's two largest cities, Montreal and Toronto. We considered several approaches to exposure assessment: (1) land use regression (LUR) models based on large-scale year-long mobile monitoring campaigns combined with detailed land use and traffic information; (2) machine learning (i.e., convolutional neural networks [CNN]) models trained by combining mobile monitoring data with aerial images; and (3) the combined use of these two approaches. We also examined exposure models with and without backcasting based on historical trends in vehicle emissions (to capture potential trends in pollutant concentrations over time) and with and without accounting for neighborhood-level mobility patterns (based on travel demand surveys). These exposure models were linked to members of the Canadian Census Health and Environment Cohorts (CanCHEC) residing in Montreal or Toronto (including census years 1991, 1996, 2001, and 2006) with mortality follow-up from 2001 (or cohort entry for the 2006 cohort) to 2016. Cox proportional hazard models were used to estimate associations between long-term exposures to outdoor UFPs and BC, adjusting for sociodemographic factors and co-pollutants identified as potential confounding factors. Concentration-response relationships for outdoor UFPs and BC were also examined for nonaccidental and cause-specific mortality using smoothing splines. RESULTS: Our cohort study included approximately 1.5 million people with 174,200 nonaccidental deaths observed during the follow-up period. Combined LUR and machine learning model predictions performed slightly better than LUR models alone and were used as the main exposure models in all epidemiological analyses. Long-term exposures to outdoor UFP number concentrations were consistently positively associated with nonaccidental and cause-specific mortality. Importantly, hazard ratios (HRs) for outdoor UFP number concentrations were sensitive to adjustment for UFP size: UFP size was inversely related to number concentrations and independently associated with mortality, resulting in underestimation of mortality risk for outdoor UFP number concentrations when UFP size was excluded. HRs for outdoor UFP number concentrations were robust to backcasting and mobility weighting but varied slightly in analyses using LUR and machine learning models alone, with stronger associations typically observed for the machine learning models. Associations between outdoor BC concentrations and mortality were generally weak or null, but a positive association was observed for cardiovascular mortality. CONCLUSIONS: Outdoor UFP number concentrations were consistently associated with increased risks of nonaccidental and cause-specific mortality in Montreal and Toronto. Our results suggest that UFP size should be considered in epidemiological analyses of outdoor UFP number concentrations, as excluding size can lead to an underestimation of health risks. Our results suggest that outdoor UFP number concentrations are positively associated with mortality independent of other outdoor air pollutants, including PM2.5 mass concentrations and oxidant gases (i.e., nitrogen dioxide [NO2] and ozone [O3]). As outdoor UFPs are currently unregulated, interventions targeting these pollutants could significantly affect population health.

Racial and Ethnic Disparities in Age-Specific All-Cause Mortality During the COVID-19 Pandemic.

Importance: The end of the COVID-19 public health emergency (PHE) provides an opportunity to fully describe pandemic-associated racial and ethnic mortality disparities. Age-specific excess mortality differences have important downstream implications, especially in minoritized race and ethnicity populations. Objectives: To characterize overall and age-specific all-cause excess mortality by race and ethnicity during the COVID-19 PHE and assess whether measured differences reflected changes from prepandemic disparities. Design, Setting, and Participants: This cross-sectional study analyzed data of all US residents and decedents during the COVID-19 PHE, aggregated by observed race and ethnicity (at time of death) and age. Statistical analysis was performed from March 2020 to May 2023. Exposures: COVID-19 PHE period (March 2020 to May 2023). Main Outcomes and Measures: All-cause excess mortality (incident rates, observed-to-expected ratios) and all-cause mortality relative risks before and during the PHE. Results: For the COVID-19 PHE period, data for 10 643 433 death certificates were available; mean (SD) decedent age was 72.7 (17.9) years; 944 318 (8.9%) were Hispanic; 78 973 (0.7%) were non-Hispanic American Indian or Alaska Native; 288 680 (2.7%) were non-Hispanic Asian, 1 374 228 (12.9%) were non-Hispanic Black or African American, 52 905 (0.5%) were non-Hispanic more than 1 race, 15 135 (0.1%) were non-Hispanic Native Hawaiian or Other Pacific Islander, and 7 877 996 (74.1%) were non-Hispanic White. More than 1.38 million all-cause excess deaths (observed-to-expected ratio, 1.15 [95% CI, 1.12-1.18]) occurred, corresponding to approximately 23 million years of potential life lost (YPLL) during the pandemic. For the total population (all ages), the racial and ethnic groups with the highest observed-to-expected all-cause mortality ratios were the American Indian or Alaska Native (1.34 [95% CI, 1.31-1.37]) and Hispanic (1.31 [95% CI, 1.27-1.34]) populations. However, higher ratios were observed in the US population aged 25 to 64 years (1.20 [95% CI, 1.18-1.22]), greatest among the American Indian or Alaska Native (1.45 [95% CI, 1.42-1.48]), Hispanic (1.40 [95% CI, 1.38-1.42]), and Native Hawaiian or Other Pacific Islander (1.39 [95% CI, 1.34-1.44]) groups. In the total population aged younger than 25 years, the Black population accounted for 51.1% of excess mortality, despite representing 13.8% of the population. Had the rate of excess mortality observed among the White population been observed among the total population, more than 252 000 (18.3%) fewer excess deaths and more than 5.2 million (22.3%) fewer YPLL would have occurred. Conclusions and Relevance: In this cross-sectional study of the US population during the COVID-19 PHE, excess mortality occurred in all racial and ethnic groups, with disparities affecting several minoritized populations. The greatest relative increases occurred in populations aged 25 to 64 years. Documented differences deviated from prepandemic disparities.

Application of a deep-learning marker for morbidity and mortality prediction derived from retinal photographs: a cohort development and validation study.

BACKGROUND: Biological ageing markers are useful to risk stratify morbidity and mortality more precisely than chronological age. In this study, we aimed to develop a novel deep-learning-based biological ageing marker (referred to as RetiPhenoAge hereafter) using retinal images and PhenoAge, a composite biomarker of phenotypic age. METHODS: We used retinal photographs from the UK Biobank dataset to train a deep-learning algorithm to predict the composite score of PhenoAge. We used a deep convolutional neural network architecture with multiple layers to develop our deep-learning-based biological ageing marker, as RetiPhenoAge, with the aim of identifying patterns and features in the retina associated with variations of blood biomarkers related to renal, immune, liver functions, inflammation, and energy metabolism, and chronological age. We determined the performance of this biological ageing marker for the prediction of morbidity (cardiovascular disease and cancer events) and mortality (all-cause, cardiovascular disease, and cancer) in three independent cohorts (UK Biobank, the Singapore Epidemiology of Eye Diseases [SEED], and the Age-Related Eye Disease Study [AREDS] from the USA). We also compared the performance of RetiPhenoAge with two other known ageing biomarkers (hand grip strength and adjusted leukocyte telomere length) and one lifestyle factor (physical activity) for risk stratification of mortality and morbidity. We explored the underlying biology of RetiPhenoAge by assessing its associations with different systemic characteristics (eg, diabetes or hypertension) and blood metabolite levels. We also did a genome-wide association study to identify genetic variants associated with RetiPhenoAge, followed by expression quantitative trait loci mapping, a gene-based analysis, and a gene-set analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and corresponding 95% CIs for the associations between RetiPhenoAge and the different morbidity and mortality outcomes. FINDINGS: Retinal photographs for 34 061 UK Biobank participants were used to train the model, and data for 9429 participants from the SEED cohort and for 3986 participants from the AREDS cohort were included in the study. RetiPhenoAge was associated with all-cause mortality (HR 1·92 [95% CI 1·42-2·61]), cardiovascular disease mortality (1·97 [1·02-3·82]), cancer mortality (2·07 [1·29-3·33]), and cardiovascular disease events (1·70 [1·17-2·47]), independent of PhenoAge and other possible confounders. Similar findings were found in the two independent cohorts (HR 1·67 [1·21-2·31] for cardiovascular disease mortality in SEED and 2·07 [1·10-3·92] in AREDS). RetiPhenoAge had stronger associations with mortality and morbidity than did hand grip strength, telomere length, and physical activity. We identified two genetic variants that were significantly associated with RetiPhenoAge (single nucleotide polymorphisms rs3791224 and rs8001273), and were linked to expression quantitative trait locis in various tissues, including the heart, kidneys, and the brain. INTERPRETATION: Our new deep-learning-derived biological ageing marker is a robust predictor of mortality and morbidity outcomes and could be used as a novel non-invasive method to measure ageing. FUNDING: Singapore National Medical Research Council and Agency for Science, Technology and Research, Singapore.

Frailty; Time for Global Action : Commentary on "Frailty and its Association with Long-Term Mortality among Community-Dwelling older adults aged 75 years and Over".

This commentary examines the study "Frailty and Its Association with Long-Term Mortality Among Community-Dwelling Older Adults Aged 75 Years and Over" by Lewis et al. The retrospective cohort study utilized data from a primary healthcare provider in Israel to investigate frailty using the Frailty Index (FI) and its correlation with long-term mortality. Nearly half of the older adult cohort was identified as frail, with a strong association between higher frailty levels and increased mortality risk. The commentary emphasizes the importance of routine frailty screening in clinical practice and health policy. Integrating FI calculations into electronic health records can facilitate timely care for high-risk individuals. However, presenting frailty data must be managed carefully and in conjunction with patients' preferences to avoid stigmatizing and negatively influencing clinical decisions. While the FI is a valuable tool, it should complement, not replace, other assessments that provide a more holistic view of the patient's health. Furthermore, the commentary strongly advocates for a more comprehensive approach to patient care, emphasizing that non-geriatricians must also be proficient in recognizing and managing frailty. Effectively addressing frailty can lead to significant cost savings for healthcare systems, reduced burden on healthcare facilities, and decreased need for long-term care.

Diurnal patterns of accelerometer-measured physical activity and sleep and risk of all-cause mortality: a follow-up of the National Health and Nutrition Examination Surveys (NHANES).

BACKGROUND: Physical activity and sleep are established modifiable lifestyle factors, but the optimal time of the day of these behaviours for health is unknown. This study examined the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality. METHODS: This prospective cohort study included 6,673 participants who have attended the accelerometer assessment in the 2011-2014 National Health and Nutrition Examination Surveys (NHANES). Diurnal patterns of accelerometer-measured physical activity and sleep were identified using K-means clustering analysis. All-cause mortality was ascertained from the accelerometer measurement to December 31, 2019 (median follow-up 6.8 years). Survey-weighted Cox proportional hazard models were performed to estimate the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality. RESULTS: Diurnal patterns identified were: early-morning (32.4%), midday (42.5%), and late-afternoon (25.1%) for physical activity; and irregular sleep (37.4%), morning lark (33.6%), and night owl (29.0%) for sleep. After adjusting for volume of physical activity, sleep duration and other potential covariates, the early-morning physical activity pattern (hazard ratio 1.36, 95% confidence interval 1.13-1.64) and irregular sleep pattern (1.42, 1.01-1.99) were independently associated with higher risk of all-cause mortality, compared with midday physical activity and morning lark sleep patterns, respectively. In addition, participants with the combined pattern of early-morning physical activity and irregular sleep had higher risk of all-cause mortality compared to those with midday physical activity combined with a morning lark sleep pattern (1.92, 1.33-2.78). Several sociodemographic differences were observed in the strength of these associations. CONCLUSIONS: Wearable activity-rest monitoring data showed that peak physical activity in the early morning and irregular sleep diurnal patterns are associated with increased mortality risk, and the combination of these patterns further exaggerated the risk. Public health program should acknowledge that the diurnal patterns of physical activity and sleep, in addition to their duration and frequency, may play a crucial role in lifestyle-based health promotion and management strategies.

Global patterns and trends of suicide mortality and years of life lost among adolescents and young adults from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021.

AIMS: We aimed to report an overview of trends in suicide mortality and years of life lost (YLLs) among adolescents and young adults aged 10-24 years by sex, age group, Socio-demographic Index (SDI), region and country from 1990 to 2021 as well as the suicide mortality with age, period and birth cohort effects. METHODS: Estimates and 95% uncertainty intervals for suicide mortality and YLLs were extracted from the Global Burden of Diseases Study 2021. Joinpoint analysis was used to calculate the annual percentage change (APC) and average annual percentage change (AAPC) to describe the mortality and rate of YLLs trends. Age, period and cohort model was utilized to disentangle age, period and birth cohort effects on suicide mortality trends. RESULTS: Globally, suicide mortality and the rate of YLLs among adolescents and young adults both declined from 1990 to 2021 (AAPC: -1.6 [-2.1 to -1.2]). In 2021, the global number of suicide death cases was 112.9 thousand [103.9-122.2 thousand] and led to 7.9 million [7.2-8.6 million] YLLs. A significant reduction in suicide mortality was observed in all sexes and age groups. By SDI quintiles, the high SDI region (AAPC: -0.3 [-0.6 to 0.0]) had the slowest decline trend, and low-middle SDI region remained the highest suicide mortality till 2021 (7.8 per 100,000 population [6.9-8.6]). Most SDI regions showed generally lower period and cohort effects during the study period, whereas high SDI region showed more unfavourable risks, especially period and cohort effects in females. Regionally, Central Latin America (AAPC: 1.7 [1.1-2.3]), Tropical Latin America (AAPC: 1.5 [0.9-2.0]), High-income Asia Pacific (AAPC: 1.2 [0.7-1.7]) and Southern sub-Saharan Africa (AAPC: 0.8 [0.4-1.2]) had the significance increase in suicide mortality. In 2021, Southern sub-Saharan Africa had the highest mortality (10.5 per 100,000 population [8.6-12.5]). Nationally, a total of 29 countries had a significant upward trend in suicide mortality and rate of YLLs over the past three decades, and certain countries in low-middle and middle regions exhibited an extremely higher burden of suicide. CONCLUSIONS: Global suicide mortality and the rate of YLLs among adolescents and young adults both declined from 1990 to 2021, but obvious variability was observed across regions and countries. Earlier mental health education and targeted management are urgently required for adolescents and young adults in certain areas.