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      Reducing and meta-analysing estimates from distributed lag non-linear models

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          Abstract

          Background

          The two-stage time series design represents a powerful analytical tool in environmental epidemiology. Recently, models for both stages have been extended with the development of distributed lag non-linear models (DLNMs), a methodology for investigating simultaneously non-linear and lagged relationships, and multivariate meta-analysis, a methodology to pool estimates of multi-parameter associations. However, the application of both methods in two-stage analyses is prevented by the high-dimensional definition of DLNMs.

          Methods

          In this contribution we propose a method to synthesize DLNMs to simpler summaries, expressed by a reduced set of parameters of one-dimensional functions, which are compatible with current multivariate meta-analytical techniques. The methodology and modelling framework are implemented in R through the packages dlnm and mvmeta.

          Results

          As an illustrative application, the method is adopted for the two-stage time series analysis of temperature-mortality associations using data from 10 regions in England and Wales. R code and data are available as supplementary online material.

          Discussion and Conclusions

          The methodology proposed here extends the use of DLNMs in two-stage analyses, obtaining meta-analytical estimates of easily interpretable summaries from complex non-linear and delayed associations. The approach relaxes the assumptions and avoids simplifications required by simpler modelling approaches.

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          Most cited references18

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          Maximum Likelihood Approaches to Variance Component Estimation and to Related Problems

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            Effects of cold weather on mortality: results from 15 European cities within the PHEWE project.

            Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.
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              Models for the relationship between ambient temperature and daily mortality.

              Ambient temperature is an important determinant of daily mortality that is of interest both in its own right and as a confounder of other determinants investigated using time-series regressions, in particular, air pollution. The temperature-mortality relationship is often found to be substantially nonlinear and to persist (but change shape) with increasing lag. We review and extend models for such nonlinear multilag forms. Popular models for mortality by temperature at given lag include polynomial and natural cubic spline curves, and the simple but more easily interpreted linear thresholds model, comprising linear relationships for temperatures below and above thresholds and a flat middle section. Most published analyses that have allowed the relationship to persist over multiple lags have done so by assuming that spline or threshold models apply to mean temperature in several lag strata (e.g., lags 0-1, 2-6, and 7-13). However, more flexible models are possible, and a modeling framework using products of basis functions ("cross-basis" functions) suggests a wide range, some used previously and some new. These allow for stepped or smooth changes in the model coefficients as lags increase. Applying a range of models to data from London suggest evidence for relationships up to at least 2 weeks' lag, with smooth models fitting best but lag-stratified threshold models allowing the most direct interpretation. A wide range of multilag nonlinear temperature-mortality relationships can be modeled. More awareness of options should improve investigation of these relationships and help control for confounding by them.
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                Author and article information

                Journal
                BMC Med Res Methodol
                BMC Med Res Methodol
                BMC Medical Research Methodology
                BioMed Central
                1471-2288
                2013
                9 January 2013
                : 13
                : 1
                Affiliations
                [1 ]Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
                [2 ]Department of Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, UK
                Article
                1471-2288-13-1
                10.1186/1471-2288-13-1
                3599933
                23297754
                e695eaad-d375-4b8d-b45e-28eb01d0f1d9
                Copyright ©2013 Gasparrini and Armstrong; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 October 2012
                : 17 December 2012
                Categories
                Research Article

                Medicine
                distributed lag models,multivariate meta-analysis,time series,two-stage analysis
                Medicine
                distributed lag models, multivariate meta-analysis, time series, two-stage analysis

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