Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis

Objective To investigate potential interactive effects of fine particulate matter (PM2.5) and ozone (O3) on daily mortality at global level. Design Two stage time series analysis. Setting 372 cities across 19 countries and regions. Population Daily counts of deaths from all causes, cardiovascular disease, and respiratory disease. Main outcome measure Daily mortality data during 1994-2020. Stratified analyses by co-pollutant exposures and synergy index (>1 denotes the combined effect of pollutants is greater than individual effects) were applied to explore the interaction between PM2.5 and O3 in association with mortality. Results During the study period across the 372 cities, 19.3 million deaths were attributable to all causes, 5.3 million to cardiovascular disease, and 1.9 million to respiratory disease. The risk of total mortality for a 10 μg/m3 increment in PM2.5 (lag 0-1 days) ranged from 0.47% (95% confidence interval 0.26% to 0.67%) to 1.25% (1.02% to 1.48%) from the lowest to highest fourths of O3 concentration; and for a 10 μg/m3 increase in O3 ranged from 0.04% (−0.09% to 0.16%) to 0.29% (0.18% to 0.39%) from the lowest to highest fourths of PM2.5 concentration, with significant differences between strata (P for interaction <0.001). A significant synergistic interaction was also identified between PM2.5 and O3 for total mortality, with a synergy index of 1.93 (95% confidence interval 1.47 to 3.34). Subgroup analyses showed that interactions between PM2.5 and O3 on all three mortality endpoints were more prominent in high latitude regions and during cold seasons. Conclusion The findings of this study suggest a synergistic effect of PM2.5 and O3 on total, cardiovascular, and respiratory mortality, indicating the benefit of coordinated control strategies for both pollutants

Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study

Background The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019.Methods The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0 & BULL;5 & DEG;x 0 & BULL;5 & DEG;. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones & GE;17 & BULL;5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects.Findings Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20 & BULL;7 (95% eCI 15 & BULL;2-26 & BULL;9) excess deaths per 100 000 residents (excess death rate) and 3 & BULL;3 (95% eCI 2 & BULL;4-4 & BULL;3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. Interpretation Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate.Australian Research Council and Australian National Health and Medical Research Council

Regional variation in the role of humidity on city-level heat-related mortality

The rising humid heat is regarded as a severe threat to human survivability, but the proper integration of humid heat into heat-health alerts is still being explored. Using state-of-the-art epidemiological and climatological datasets, we examined the association between multiple heat stress indicators (HSIs) and daily human mortality in 739 cities worldwide. Notable differences were observed in the long-term trends and timing of heat events detected by HSIs. Air temperature (Tair) predicts heat-related mortality well in cities with a robust negative Tair-relative humidity correlation (CT-RH). However, in cities with near-zero or weak positive CT-RH, HSIs considering humidity provide enhanced predictive power compared to Tair. Furthermore, the magnitude and timing of heat-related mortality measured by HSIs could differ largely from those associated with Tair in many cities. Our findings provide important insights into specific regions where humans are vulnerable to humid heat and can facilitate the further enhancement of heat-health alert systems. © The Author(s) 2024.Q.G., M.H., and T.O. were supported by the Environment Research and Technology Development Fund (JPMEERF23S21120) of the Environmental Restoration and Conservation Agency provided by the Ministry of the Environment of Japan. Q.G. was supported by the Musha Shugyo international travel grants from the School of Engineering, The University of Tokyo. T.O. was supported by the Japan Society for the Promotion of Science (KAKENHI: 21H05002), and the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan (JPMEERF23S21100). M.N.M. was supported by the European Commission (H2020-MSCA-IF-2020) under REA grant agreement no. 101022870. A.G. was supported by the Medical Research Council-UK (Grant ID: MR/V034162/1) and European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). J.K. was supported by the Czech Science Foundation, project 23-06749S. A.M.V.-C. supported by the Swiss National Science Foundation (TMSGI3_211626). V.H. was supported by the European Union’s Horizon 2020 research and innovation program (H2020-MSCA-IF-2020, Grant No.: 101032087). Y.S. was supported by Brain Pool Plus program funded by the Ministry of Science and ICT through the National Research Foundation of Korea (NRF-2021H1D3A2A03097768), and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2023R1A2C1004754)

Seasonal variation in mortality and the role of temperature: a multi-country multi-city study

Data availability: Data have been collected within the MCC (Multi-Country Multi-City) Collaborative Research Network (https://mccstudy.lshtm.ac.uk) under a data-sharing agreement and cannot be made publicly available. The R code for the analysis is available from the first author.Copyright . Background: Although seasonal variations in mortality have been recognized for millennia, the role of temperature remains unclear. We aimed to assess seasonal variation in mortality and to examine the contribution of temperature. Methods: We compiled daily data on all-cause, cardiovascular and respiratory mortality, temperature and indicators on location-specific characteristics from 719 locations in tropical, dry, temperate and continental climate zones. We fitted time-series regression models to estimate the amplitude of seasonal variation in mortality on a daily basis, defined as the peak-to-trough ratio (PTR) of maximum mortality estimates to minimum mortality estimates at day of year. Meta-analysis was used to summarize location-specific estimates for each climate zone. We estimated the PTR with and without temperature adjustment, with the differences representing the seasonal effect attributable to temperature. We also evaluated the effect of location-specific characteristics on the PTR across locations by using meta-regression models. Results: Seasonality estimates and responses to temperature adjustment varied across locations. The unadjusted PTR for all-cause mortality was 1.05 [95% confidence interval (CI): 1.00–1.11] in the tropical zone and 1.23 (95% CI: 1.20–1.25) in the temperate zone; adjusting for temperature reduced the estimates to 1.02 (95% CI: 0.95–1.09) and 1.10 (95% CI: 1.07–1.12), respectively. Furthermore, the unadjusted PTR was positively associated with average mean temperature. Conclusions: This study suggests that seasonality of mortality is importantly driven by temperature, most evidently in temperate/continental climate zones, and that warmer locations show stronger seasonal variations in mortality, which is related to a stronger effect of temperature.This work was primarily supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI [Grant Number 19K19461]. Y.C. was supported by a Senior Research grant [2019R1A2C1086194] from the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (Information and Communication Technologies). V.H. received support from the Spanish Ministry of Economy, Industry and Competitiveness [Grant ID: PCIN-2017-046]. J.K. and A.U. were supported by the Czech Science Foundation [project 18-22125S]. A.S. acknowledged funding from European Union’s Horizon 2020 research and innovation programme under grant agreement No 820655 (EXHAUSTION). A.G. was supported by the Medical Research Council-UK [Grant ID: MR/R013349/1], the Natural Environment Research Council UK [Grant ID: NE/R009384/1] and the European Union’s Horizon 2020 Project Exhaustion [Grant ID: 820655]. M.H. was supported by the Japan Science and Technology Agency (JST) as part of SICORP [Grant Number JPMJSC20E4]

Seasonality of mortality under climate change: a multicountry projection study

Data sharing: All data used in our study were obtained from the MCC Collaborative Research Network under a data-sharing agreement and cannot be made publicly available. Researchers can refer to collaborators of the Network, who are listed as coauthors of this Article (primary contact: Antonio Gasparrini, [email protected]), for information on accessing the data for each country. The R code is available on request, and a reproducible example is publicly available on the personal GitHub website of the first author (https://github.com/LinaMadaniyazi).For more on the MCC see https://mccstudy.lshtm.ac.uk/Supplementary Material is available online at: https://www.sciencedirect.com/science/article/pii/S2542519623002693#sec1 .Background: Climate change can directly impact temperature-related excess deaths and might subsequently change the seasonal variation in mortality. In this study, we aimed to provide a systematic and comprehensive assessment of potential future changes in the seasonal variation, or seasonality, of mortality across different climate zones. Methods: In this modelling study, we collected daily time series of mean temperature and mortality (all causes or non-external causes only) via the Multi-Country Multi-City Collaborative (MCC) Research Network. These data were collected during overlapping periods, spanning from Jan 1, 1969 to Dec 31, 2020. We projected daily mortality from Jan 1, 2000 to Dec 31, 2099, under four climate change scenarios corresponding to increasing emissions (Shared Socioeconomic Pathways [SSP] scenarios SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). We compared the seasonality in projected mortality between decades by its shape, timings (the day-of-year) of minimum (trough) and maximum (peak) mortality, and sizes (peak-to-trough ratio and attributable fraction). Attributable fraction was used to measure the burden of seasonality of mortality. The results were summarised by climate zones. Findings: The MCC dataset included 126 809 537 deaths from 707 locations within 43 countries or areas. After excluding the only two polar locations (both high-altitude locations in Peru) from climatic zone assessments, we analysed 126 766 164 deaths in 705 locations aggregated in four climate zones (tropical, arid, temperate, and continental). From the 2000s to the 2090s, our projections showed an increase in mortality during the warm seasons and a decrease in mortality during the cold seasons, albeit with mortality remaining high during the cold seasons, under all four SSP scenarios in the arid, temperate, and continental zones. The magnitude of this changing pattern was more pronounced under the high-emission scenarios (SSP3-7.0 and SSP5-8.5), substantially altering the shape of seasonality of mortality and, under the highest emission scenario (SSP5-8.5), shifting the mortality peak from cold seasons to warm seasons in arid, temperate, and continental zones, and increasing the size of seasonality in all zones except the arid zone by the end of the century. In the 2090s compared with the 2000s, the change in peak-to-trough ratio (relative scale) ranged from 0·96 to 1·11, and the change in attributable fraction ranged from 0·002% to 0·06% under the SSP5-8.5 (highest emission) scenario. Interpretation: A warming climate can substantially change the seasonality of mortality in the future. Our projections suggest that health-care systems should consider preparing for a potentially increased demand during warm seasons and sustained high demand during cold seasons, particularly in regions characterised by arid, temperate, and continental climates.This study was primarily supported by the Environment Research and Technology Development Fund (grant number JPMEERF20231007) of the Environmental Restoration and Conservation Agency, provided by the Ministry of the Environment of Japan. MH was supported by the Japan Science and Technology Agency as part of the Strategic International Collaborative Research Program (grant number JPMJSC20E4). AG was supported by the UK Medical Research Council (grant number MR/V034162/1) and the EU's Horizon 2020 research project Exhaustion (grant number 820655). AU and JK were supported by the Czech Science Foundation (project 22–24920S). JJKJ was supported by the Academy of Finland (grant number 310372; Global Health Risks Related to Atmospheric Composition and Weather Consortium). FS was supported by the Italian Ministry of University and Research, Department of Excellence project 2023–2027, Rethinking Data Science—Department of Statistics, Computer Science and Applications—University of Florence

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections