An extended mixed‐effects framework for meta‐analysis

Sera, Francesco; Armstrong, Ben; Blangiardo, Marta; Gasparrini, Antonio

doi:10.1002/sim.8362

Cited by 198 publications

(160 citation statements)

References 78 publications

(215 reference statements)

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“…In the second stage, we used a new multilevel meta-analytical approach to summarise the city specific associations 16. Briefly, this model defines more complex random effects structures that account for the hierarchical structure of the data—namely, cities nested within countries, and provides the best linear unbiased predictors for the associations between NO 2 and mortality at both levels 16. We computed the global, country, and city specific estimates and 95% confidence intervals as percentage change in daily mortality per 10 μg/m 3 increase of NO 2 concentrations.…”

Section: Methodsmentioning

confidence: 99%

Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities

Meng

Liu

Chen

et al. 2021

BMJ

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130

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Objective To evaluate the short term associations between nitrogen dioxide (NO 2 ) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting 398 cities in 22 low to high income countries/regions. Main outcome measures Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results On average, a 10 μg/m 3 increase in NO 2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM 10 and PM 2.5 , respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO 2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO 2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO 2 .

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Section: Methodsmentioning

confidence: 99%

Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities

Meng

Liu

Chen

et al. 2021

BMJ

Self Cite

130

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“…The general statistical framework applied here is an extension of the classic two stage design6 and incorporates complex multivariable associations, hierarchical pooling methods, and the computation of impact measures 181920. Briefly, we first estimated city specific ozone-mortality risks from separate time series regression models and then pooled these through a meta-analysis in the second stage.…”

Section: Methodsmentioning

confidence: 99%

“…In the second stage we pooled city specific estimates through a multilevel meta-analysis. This novel meta-analytical model defines more complex random effects that can account for variations in risk across two nested grouping levels, represented by cities within countries 19. This approach allowed the derivation of improved estimates of ozone-mortality associations at both city and country level, defined as best linear unbiased predictions.…”

Section: Methodsmentioning

confidence: 99%

Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

Vicedo‐Cabrera

Sera

Liu

et al. 2020

BMJ

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145

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OBJECTIVE To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide. DESIGNTwo stage time series analysis.SETTING 406 cities in 20 countries, with overlapping periods between 1985 and 2015, collected from the database of Multi-City Multi-Country Collaborative Research Network. POPULATIONDeaths for all causes or for external causes only registered in each city within the study period. MAIN OUTCOME MEASURESDaily total mortality (all or non-external causes only). RESULTSA total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 µg/m 3 increase in ozone during the current and previous day was associated with an overall relative risk of mortality of 1.0018 (95% confidence interval 1.0012 to 1.0024). Some heterogeneity was found across countries, with estimates ranging from greater than 1.0020 in the United Kingdom, South Africa, Estonia, and Canada to less than 1.0008 in Mexico and Spain. Short term excess mortality in association with exposure to ozone higher than maximum background levels (70 µg/ m 3 ) was 0.26% (95% confidence interval 0.24% to 0.28%), corresponding to 8203 annual excess deaths (95% confidence interval 3525 to 12 840) across the 406 cities studied. The excess remained at 0.20% (0.18% to 0.22%) when restricting to days above the WHO guideline (100 µg/m 3 ), corresponding to 6262 annual excess deaths (1413 to 11 065). Above more lenient thresholds for air quality standards in Europe, America, and China, excess mortality was 0.14%, 0.09%, and 0.05%, respectively. CONCLUSIONSResults suggest that ozone related mortality could be potentially reduced under stricter air quality standards. These findings have relevance for the implementation of efficient clean air interventions and mitigation strategies designed within national and international climate policies.Cite this as: BMJ 2020;368:m108 http://dx. WHAT IS ALREADY KNOWN ON THIS TOPICStudies on the short term association between ground level ozone and mortality have been mostly performed in a few locations, in limited geographical areas, and using various designs and modelling approaches Although most of the studies found positive associations, results are heterogeneous, and a critical comparison across different countries and regions is made difficult by the limited statistical power and differences across studies Estimates of the association are usually reported as relative risks, a summary measure that does not quantify the actual health impact and makes it difficult to evaluate comparative health benefits of different regulatory limits WHAT THIS STUDY ADDSThis large multi-country study found increased mortality risks associated with exposure to ozone across locations and countries, with an average 0.18% per 10 µg/m3, reinforcing the evidence of a potential causal association Risk estimates were translated in measures of excess mortality, and it was found that more than 6000 deaths each year, corresponding to 0.20% of the total mortality, would have been avoided in the...

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“…The province-specific coefficients of the function defining the excess risk were then pooled in the second stage using a mixed-effects multivariate meta-analysis, 18 and best linear unbiased predictions for each of the 107 provinces were extracted. This approach allows borrowing strengths in the estimates across provinces, while at the same time modelling flexible associations of multi-parameter functions.…”

Section: Methodsmentioning

confidence: 99%

Excess mortality during the COVID-19 outbreak in Italy: a two-stage interrupted time series analysis

Scortichini

Santos

Donato

et al. 2020

Preprint

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Background: Italy was the first country outside China to experience the impact of the COVID-19 pandemic, which resulted in a significant health burden. This study presents an analysis of the excess mortality across the 107 Italian provinces, stratified by sex, age group, and period of the outbreak. Methods: The analysis was performed using a two-stage interrupted time series design using daily mortality data for the period January 2015 - May 2020. In the first stage, we performed province-level quasi-Poisson regression models, with smooth functions to define a baseline risk while accounting for trends and weather conditions and to flexibly estimate the variation in excess risk during the outbreak. Estimates were pooled in the second stage using a mixed-effects multivariate meta-analysis. Results: In the period 15 February - 15 May 2020, we estimated an excess of 47,490 (95% empirical confidence intervals: 43,984 to 50,362) deaths in Italy, corresponding to an increase of 29.5% (95%eCI: 26.8 to 31.9%) from the expected mortality. The analysis indicates a strong geographical pattern, with the majority of excess deaths occurring in northern regions, where few provinces experienced up to 800% increase during the peak in late March. There were differences by sex, age, and area both in the overall impact and in its temporal distribution. Conclusions: This study offers a detailed picture of excess mortality during the first months of the COVID-19 pandemic in Italy. The strong geographical and temporal patterns can be related to implementation of lockdown policies and multiple direct and indirect pathways in mortality risk.

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An extended mixed‐effects framework for meta‐analysis

Cited by 198 publications

References 78 publications

Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities

Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities

Short term association between ozone and mortality: global two stage time series study in 406 locations in 20 countries

Excess mortality during the COVID-19 outbreak in Italy: a two-stage interrupted time series analysis

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