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Objective To evaluate the short term associations between nitrogen dioxide (NO2) 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/m3 increase in NO2 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 (PM10 and PM2.5, 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 NO2 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 NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2., HaK was supported by the National Natural Science Foundation of China (92043301, 82030103, and 91843302) and China Medical Board Collaborating Program (16-250). AG and FS were supported by the Medical Research Council, UK (MR/M022625/1), the Natural Environment Research Council, UK (NE/R009384/1), and the European Union’s Horizon 2020 Project Exhaustion (820655). VH was supported by the Spanish Ministry of Science and Innovation (PCIN-2017-046), and the German Federal Ministry of Education and Research (01LS1201A2). YH and MH were supported by the Environment Research and Technology Development Fund (JPMEERF15S11412) of the Environmental Restoration and Conservation Agency, Japan. JK and AU were supported by the Czech Science Foundation (18-22125S). ST was supported by the Shanghai Municipal Science and Technology Commission (18411951600). Y-LLG was supported by a Career Development Fellowship of the Australian National Health and Medical Research Council (APP1163693). SL was supported by an Early Career Fellowship of the Australian National Health and Medical Research Council (APP1109193). JJKJJ and NR were supported by the Academy of Finland (310372). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

IntroductionInternal temporomandibular joint (TMJ) disorders are present in approximately 80% of patients with symptomatic temporomandibular disorders. Among the minimally invasive therapies, we find the intra-articular infiltration of substances, such as corticosteroids, hyaluronic acid or platelet-rich plasma accompanied or not by an arthrocentesis. There are several studies on minimally invasive therapy for internal TMJ disorders; however, none compares the effectiveness of the different intra-articular corticosteroids to each other.The purpose of this study is to evaluate the effectiveness of the different intra-articular corticosteroids for the treatment of internal disorders of the TMJ and compare them to each other or to other minimally invasive therapies.Methods and analysisA systematic search will be carried out up to December 2019 in the electronic databases: Medline, Cochrane Library, EMBASE, SCOPUS and LILACS.Randomised clinical trials evaluating patients with internal disorders of the TMJ, with intra-articular corticosteroid therapy and comparing these to each other and/or to other minimally invasive therapy will be included. The main outcomes will be pain and range of motion measured through validated scales.Two review authors will independently screen search results, extract data from included studies and assess the risk of bias in those studies using the Revised Cochrane Risk of Bias Tool (RoB 2.0). In the case of any discrepancy and failure to reach consensus, this will be resolved by a third reviewer.A network meta-analysis will be conducted based on direct comparisons to generate indirect comparisons of the different treatments. Data will be combined in a meta-analysis using a random effects model.The principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to assess the overall quality of the body of evidence associated with the main results.Ethics and disseminationThis protocol will not require ethical approval. The results of this review will be disseminated through peer-reviewed publications.Trial registration numberCRD42019129014.

Objective To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide. Design Two 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. Population Deaths for all causes or for external causes only registered in each city within the study period. Main outcome measures Daily total mortality (all or non-external causes only). Results A total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 µg/m3 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/m3) 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/m3), 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. Conclusions Results 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., Funding: This work was primarily supported by the UK Medical Research Council (MR/M022625/1 and MR/R013349/1) and by the UK Natural Environment Research Council (NE/R009384/1). HaK was supported by the National Natural Science Foundation of China (91843302 and 91643205) and China Medical Board Collaborating Program (16-250). JM was supported by the Fundação para a Ciência e a Tecnologia (FCT) through the scholarship SFRH/BPD/115112/2016. VH was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO, PCIN-2017-046) and the German Federal Ministry of Education and Research (BMBF, 01LS1201A2). AU and JK were supported by the Czech Science Foundation (18-22125S). HO and EI were supported by the Estonian Ministry of Education and Research (IUT34-17). AT was supported by the Japanese Society for the Promotion of Science invitational fellowships for research in Japan (S18149). YG was supported by the career development fellowship of the Australian National Health and Medical Research Council (APP1107107 and APP1163693). ST was supported by the Science and Technology Commission of Shanghai Municipality (18411951600). HoK was supported by the Global Research Laboratory (#K21004000001-10A0500-0710) through the National Research Foundation of Korea and by the Future Planning and Korea Ministry of Environment as the “Climate Change Correspondence R&D Program” (2013001310002). RMG was supported by a CSIR parliamentary grant. NS is supported by the National Institute of Environmental Health Sciences funded HERCULES Centre (P30ES019776). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this manuscript.

Background To perform a costebenefit analysis of the installation of speed cameras on the beltways of Barcelona. Methods The analysis was performed from the society perspective over a 2-year period using a controlled before-and-after study design. The net benefit was calculated using, as benefits, the willingness to pay for the estimated number of people who avoided injury as a consequence of the intervention, subtracting costs and savings. Sensitivity analyses were performed using the maximum and minimum estimated number of people who avoided injury, assuming that there was a minimum of one death avoided, using the maximum value of a statistical life, assigning all implementation costs to the first year and assuming there was no time lost due to speed reduction. Results Base case results showed a net benefit of €6.8 million. Sensitivity analyses suggested that net benefits could range from €5.6 to €23.1 million over 2 years. Conclusions The use of speed cameras in urban areas has a favourable economic impact even when assessed using conservative assumptions.

Background: This paper aims at assessing the effectiveness of the package of road safety measures implemented after road safety was included in the political agenda in the year 2004 on the number of road traffic-injured people in Spain. Methods: An evaluation study was performed using an interrupted time-series design. The study population was people injured in road traffic crashes in Spain between 1 January 2000 and 31 December 2006. The road traffic crashes database of the General Directorate for Traffic was used. The dependent variable was the monthly number of people injured, stratified by sex, age, severity and type of road user. The explanatory variable (intervention) compared the post-intervention period (2004-6) with the pre-intervention period (2000-3). Quasi-Poisson regression models were adjusted, controlling for time trend and for seasonality. Results: Results show a reduction in the risk of being injured for both men (RR 0.91; 95% CI 0.87 to 0.95) and women (RR 0.89; 95% CI 0.85 to 0.94). Risk reductions were observed across all age groups and all road users, except for pedestrians. Conclusions: The present study suggests that prioritising road safety reduces the number of people injured in road traffic collisions., his work was supported by the Agencia Española de Tecnologías Sanitarias (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I) e Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación) (PI07/90157). The funding source has not had any involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the paper for publication.

Background: Despite the fact that airborne pollen is an important factor in precipitating asthma attacks, its implication in increases of epidemic asthma in usual meteorological conditions has not been reported. A study was undertaken to estimate the relationship between various types of aeroallergens and seasonal epidemic asthma in the region of Madrid, Spain. Methods: A case-control study was carried out in individuals aged 4-79 years who received emergency healthcare for asthma during 2001 in a base hospital covering a population of 750 000 inhabitants of Madrid. A skin prick test was performed with grass pollen, plantain pollen, olive pollen, cypress pollen, plane tree pollen, dust mites and Alternaria and the prevalence of skin reactivity was compared between subjects with asthma requiring emergency care for asthma within (cases) and outside (controls) the seasonal epidemic period. Data were analysed using logistic regression adjusting for age and sex. Results: The response rate was 61.7% for cases (n=95) and 51.6% for controls (n=146). The OR of sensitisation to grass pollen for cases compared with controls was 9.9 (95% CI 4.5 to 21.5); plantain pollen: 4.5 (95% CI 2.5 to 8.2); olive pollen: 7.3 (95% CI 3.5 to 15.2); plane tree pollen: 3.6 (95% CI 2.0 to 6.4); cypress pollen: 3.5 (95% CI 2.0 to 6.2); dust mites: 1.1 (95% CI 0.6 to 1.9); Alternaria: 0.9 (95% CI 0.5 to 1.9). The association with grasses was maintained after adjusting simultaneously for the remaining aeroallergens (OR 5.0 (95% CI 1.5 to 16.4)); this was the only one that retained statistical significance (p=0.007). Conclusions: These results suggest that allergy to pollen, particularly grass pollen, is associated with the epidemic increase in asthma episodes during the months of May and June in the Madrid area of Spain.

Objective To assess the effectiveness of speed cameras in reducing the numbers of crashes and people injured on the arterial roads of Barcelona, and to assess their long-term effectiveness on the beltway. Methods Time series analyses were performed separately for the arterial roads and the beltway. The stretches of arterial roads encompassing 500 m before and after the location of a speed camera were considered the enforced stretches, the remaining stretches of arterial roads being considered the comparison group. The outcome measures were the numbers of crashes and of people injured. Quasi-Poisson regression models were fitted, controlling for time trend, seasonality and implementation of other road safety measures. Results Both on the enforced and non-enforced arterial road stretches, the risks of crashes and people injured were similar in the two periods. On the beltway, reductions of 30% (95% CI 38% to 20%) and 26% (95% CI 36% to 14%) were observed, respectively. Conclusions Speed cameras do not reduce the numbers of crashes or people injured on the arterial roads of Barcelona. However, they are effective in the short and in the long-term on the beltway. Speed enforcement through fixed speed cameras is thus effective in mediumehigh-speed roads, although effectiveness could not be generalised to roads with lower speed limits and traffic lights.

Study objective-The objective of this paper is to introduce a different approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. Design-The approach is illustrated by providing quantitative estimates of the short-term effects of air pollution on mortality in three Spanish cities, Barcelona, Valencia and Vigo, for the period 1992-1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were nonlinear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. Main results-The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 mug/m(3) and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 mug/m(3) of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant, especially those among air pollutants and meteorological variables. Conclusions-Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities.