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

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

Heat and risk of myocardial infarction: hourly level case-crossover analysis of MINAP database.

OBJECTIVE: To quantify the association between exposure to higher temperatures and the risk of myocardial infarction at an hourly temporal resolution. DESIGN: Case-crossover study. SETTING: England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. PARTICIPANTS: 24,861 hospital admissions for myocardial infarction occurring in 11 conurbations during the warmest months (June to August) of the years 2003-09. MAIN OUTCOME MEASURE: Odds ratio of myocardial infarction for a 1 °C increase in temperature. RESULTS: Strong evidence was found for an effect of heat acting 1-6 hours after exposure to temperatures above an estimated threshold of 20 °C (95% confidence interval 16 °C to 25 °C). For each 1 °C increase in temperature above this threshold, the risk of myocardial infarction increased by 1.9% (0.5% to 3.3%, P=0.009). Later reductions in risk seemed to offset early increases in risk: the cumulative effect of a 1 °C rise in temperature above the threshold was 0.2% (-2.1% to 2.5%) by the end of the third day after exposure. CONCLUSIONS: Higher ambient temperatures above a threshold of 20 °C seem to be associated with a transiently increased risk of myocardial infarction 1-6 hours after exposure. Reductions in risk at longer lags are consistent with heat triggering myocardial infarctions early in highly vulnerable people who would otherwise have had a myocardial infarction some time later ("short term displacement"). Policies aimed at reducing the health effects of hot weather should include consideration of effects operating at sub-daily timescales

Mental health impacts of flooding: a controlled interrupted time series analysis of prescribing data in England.

BACKGROUND: There is emerging evidence that people affected by flooding suffer adverse impacts on their mental well-being, mostly based on self-reports. METHODS: We examined prescription records for drugs used in the management of common mental disorder among primary care practices located in the vicinity of recent large flood events in England, 2011-2014. A controlled interrupted time series analysis was conducted of the number of prescribing items for antidepressant drugs in the year before and after the flood onset. Pre-post changes were compared by distance of the practice from the inundated boundaries among 930 practices located within 10 km of a flood. RESULTS: After control for deprivation and population density, there was an increase of 0.59% (95% CI 0.24 to 0.94) prescriptions in the postflood year among practices located within 1 km of a flood over and above the change observed in the furthest distance band. The increase was greater in more deprived areas. CONCLUSIONS: This study suggests an increase in prescribed antidepressant drugs in the year after flooding in primary care practices close to recent major floods in England. The degree to which the increase is actually concentrated in those flooded can only be determined by more detailed linkage studies

Brief Report: Investigating Uncertainty in the Minimum Mortality Temperature: Methods and Application to 52 Spanish Cities.

BACKGROUND: The minimum mortality temperature from J- or U-shaped curves varies across cities with different climates. This variation conveys information on adaptation, but ability to characterize is limited by the absence of a method to describe uncertainty in estimated minimum mortality temperatures. METHODS: We propose an approximate parametric bootstrap estimator of confidence interval (CI) and standard error (SE) for the minimum mortality temperature from a temperature-mortality shape estimated by splines. RESULTS: The coverage of the estimated CIs was close to nominal value (95%) in the datasets simulated, although SEs were slightly high. Applying the method to 52 Spanish provincial capital cities showed larger minimum mortality temperatures in hotter cities, rising almost exactly at the same rate as annual mean temperature. CONCLUSIONS: The method proposed for computing CIs and SEs for minimums from spline curves allows comparing minimum mortality temperatures in different cities and investigating their associations with climate properly, allowing for estimation uncertainty

The effects of hourly differences in air pollution on the risk of myocardial infarction: case crossover analysis of the MINAP database.

OBJECTIVES: To investigate associations between air pollution levels and myocardial infarction (MI) on short timescales, with data at an hourly temporal resolution. DESIGN: Time stratified case crossover study linking clinical data from the Myocardial Ischaemia National Audit Project (MINAP) with PM(10), ozone, CO, NO(2), and SO(2) data from the UK National Air Quality Archive. Pollution effects were investigated with delays (lags) of 1-6, 7-12, 13-18, 19-24, and 25-72 hours in both single and multi-pollutant models, adjusted for ambient temperature, relative humidity, circulating levels of influenza and respiratory syncytial virus, day of week, holidays, and residual seasonality within calendar month strata. SETTING: Population based study in 15 conurbations in England and Wales. SUBJECTS: 79,288 diagnoses of myocardial infarction recorded over the period 2003-6. MAIN OUTCOME MEASURES: Excess risk of myocardial infarction per 10 µg/m(3) increase in pollutant level. RESULTS: In single pollutant models, PM(10) and NO(2) levels were associated with a very short term increase in risk of myocardial infarction 1-6 hours later (excess risks 1.2% (95% confidence interval 0.3 to 2.1) and 1.1% (0.3 to 1.8) respectively per 10 μg/m(3) increase); the effects persisted in multi-pollutant models, though with only weak evidence of an independent PM(10) effect (P = 0.05). The immediate risk increases were followed by reductions in risk at longer lags: we found no evidence of any net excess risk associated with the five pollutants studied over a 72 hour period after exposure. CONCLUSIONS: Higher levels of PM(10) and NO(2), which are typically markers of traffic related pollution, seem to be associated with transiently increased risk of myocardial infarction 1-6 hours after exposure, but later reductions in risk suggest that air pollution may be associated with bringing events forward in time ("short-term displacement") rather than increasing overall risk. The well established effect of air pollution on cardiorespiratory mortality may not be mediated through increasing the acute risk of myocardial infarction, but through another mechanism

Risk of asthmatic episodes in children exposed to sulfur dioxide stack emissions from a refinery point source in Montreal, Canada.

BACKGROUND: Little is known about the respiratory effects of short-term exposures to petroleum refinery emissions in young children. This study is an extension of an ecologic study that found an increased rate of hospitalizations for respiratory conditions among children living near petroleum refineries in Montreal (Canada). METHODS: We used a time-stratified case-crossover design to assess the risk of asthma episodes in relation to short-term variations in sulfur dioxide levels among children 2-4 years of age living within 0.5-7.5 km of the refinery stacks. Health data used to measure asthma episodes included emergency department (ED) visits and hospital admissions from 1996 to 2004. We estimated daily levels of SO2 at the residence of children using a) two fixed-site SO2 monitors located near the refineries and b) the AERMOD (American Meteorological Society/Environmental Protection Agency Regulatory Model) atmospheric dispersion model. We used conditional logistic regression to estimate odds ratios associated with an increase in the interquartile range of daily SO2 mean and peak exposures (31.2 ppb for AERMOD peaks). We adjusted for temperature, relative humidity, and regional/urban background air pollutant levels. RESULTS: The risks of asthma ED visits and hospitalizations were more pronounced for same-day (lag 0) SO2 peak levels than for mean levels on the same day, or for other lags: the adjusted odds ratios estimated for same-day SO2 peak levels from AERMOD were 1.10 [95% confidence interval (CI), 1.00-1.22] and 1.42 (95% CI, 1.10-1.82), over the interquartile range, for ED visits and hospital admissions, respectively. CONCLUSIONS: Short-term episodes of increased SO2 exposures from refinery stack emissions were associated with a higher number of asthma episodes in nearby children

Extremely cold and hot temperatures increase the risk of ischaemic heart disease mortality: epidemiological evidence from China.

OBJECTIVE: To examine the effects of extremely cold and hot temperatures on ischaemic heart disease (IHD) mortality in five cities (Beijing, Tianjin, Shanghai, Wuhan and Guangzhou) in China; and to examine the time relationships between cold and hot temperatures and IHD mortality for each city. DESIGN: A negative binomial regression model combined with a distributed lag non-linear model was used to examine city-specific temperature effects on IHD mortality up to 20 lag days. A meta-analysis was used to pool the cold effects and hot effects across the five cities. PATIENTS: 16 559 IHD deaths were monitored by a sentinel surveillance system in five cities during 2004-2008. RESULTS: The relationships between temperature and IHD mortality were non-linear in all five cities. The minimum-mortality temperatures in northern cities were lower than in southern cities. In Beijing, Tianjin and Guangzhou, the effects of extremely cold temperatures were delayed, while Shanghai and Wuhan had immediate cold effects. The effects of extremely hot temperatures appeared immediately in all the cities except Wuhan. Meta-analysis showed that IHD mortality increased 48% at the 1st percentile of temperature (extremely cold temperature) compared with the 10th percentile, while IHD mortality increased 18% at the 99th percentile of temperature (extremely hot temperature) compared with the 90th percentile. CONCLUSIONS: Results indicate that both extremely cold and hot temperatures increase IHD mortality in China. Each city has its characteristics of heat effects on IHD mortality. The policy for response to climate change should consider local climate-IHD mortality relationships

The importance of financial market development on the relationship between loan guarantees for SMEs and local market employment rates

We empirically examine whether a major government intervention in the small-firm credit market yields significantly better results in markets that are less financially developed. The government intervention that we investigate is SBA-guaranteed lending. The literature on financing small and medium size enterprises (SMEs) suggests that small firms may be exposed to a particular type of market failure associated with credit rationing. And SMEs in markets that are less financially developed will likely face a greater degree of this market failure. To test our hypothesis, we use the level of bank deposits per capita as our relative measure of financial market development, and we use local market employment rates as our measure of economic performance. After controlling for the appropriate cross-sectional market characteristics, we find that SBA-guaranteed lending has a significantly more (less) positive impact on the average annual level of employment when the local market is relatively less (more) financially developed. This result has important implications for public policy directives concerning where SBA-guaranteed lending should be directed.Small Business Administration ; Financial markets ; Small business - Finance ; Employment

Longer-Term Impact of Highand Low Temperature on Mortality: An International Study to Clarify Length of Mortality Displacement

In many places, daily mortality has been shown to increase after days with particularly high or low temperatures, but such daily time-series studies cannot identify whether such increases reflect substantial life shortening or short-term displacement of deaths (harvesting)