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Purpose To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. Methods The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation. Results 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO 2 /FiO 2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. Conclusions Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. Trial Registration: ClinicalTrials.gov NCT02010073.

ObjectivesTo update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort.MethodsVital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration.ResultsCompared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD).ConclusionsThis update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

ObjectivesSeveral observational studies have suggested an association between high temperatures and all-cause mortality. However, estimates on more specific mortality outcomes are sparse, and frequently assessed in studies using different analytical methods.MethodsA time series analysis was performed on 10 regions in England and Wales during the summers (June–September) of 1993–2006. Average percentage linear increases in risk for a 1°C increase in temperature above region-specific thresholds and attributable deaths were computed by cause-specific mortality and age groups (0–64, 65–74, 75–84, 85+).ResultsThere was evidence of increased mortality with heat for almost all cause-of-death groups examined, with an overall increase in all-cause mortality of 2.1% (95% CI 1.6% to 2.6%) for a 1°C rise above the regional heat threshold. Among main causes, the steepest increase in risk was for respiratory mortality (+4.1% (3.5% to 4.8%) per 1°C). It was much smaller for cardiovascular causes (+1.8% (1.2% to 2.5%)) and myocardial infarction (+1.1% (0.7% to 1.5%)), but comparatively high for arrhythmias (+5.0% (3.2% to 6.9%)) and pulmonary heart disease (+8.3% (2.7% to 14.3%)). Among non- cardiorespiratory causes, the strongest effects were for genitourinary (+3.8% (2.9% to 4.7%)) and nervous system (+4.6% (3.7% to 5.4%)) disorders. 33.9% of heat deaths were attributable to cardiovascular causes, 24.7% to respiratory causes and 41.3% to all other causes combined.ConclusionsThese results suggest that the risk of heat-related mortality is distributed across a wide range of different causes, and that targeting of preventative actions based on pre-existing disease is unlikely to be efficient.

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians.Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability.Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh).Participants 1 124 897 men and women (mean age 53.4 years at baseline).Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes.Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12).Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

The International Nuclear Workers Study (INWORKS) contributes knowledge on the dose-response association between predominantly low dose, low dose rate occupational exposures to penetrating forms of ionizing radiation and cause-specific mortality. By extending follow-up of 309,932 radiation workers from France (1968–2014), the United Kingdom (1955–2012), and the United States (1944–2016) we increased support for analyses of temporal variation in radiation-cancer mortality associations. Here, we examine whether age at exposure, time since exposure, or attained age separately modify associations between radiation and mortality from all solid cancers, solid cancers excluding lung cancer, lung cancer, and lymphohematopoietic cancers. Multivariable Poisson regression was used to fit general relative rate models that describe modification of the linear excess relative rate per unit organ absorbed dose. Given indication of greater risk per unit dose for solid cancer mortality among workers hired in more recent calendar years, sensitivity analyses considering the impact of year of hire on results were performed. Findings were reasonably compatible with those from previous pooled and country-specific analyses within INWORKS showing temporal patterns of effect measure modification that varied among cancers, with evidence of persistent radiation-associated excess cancer risk decades after exposure, although statistically significant temporal modification of the radiation effect was not observed. Analyses stratified by hire period (< 1958, 1958+) showed temporal patterns that varied; however, these analyses did not suggest that this was due to differences in distribution of these effect measure modifiers by hire year.

ObjectivesTo examine associations between occupational exposures to rubber dust, rubber fumes and N-nitrosamines and non-cancer mortality.MethodsA cohort of 36 441 males aged 35+ years employed in British rubber factories was followed-up to 2015 (94% deceased). Competing risk survival analysis was used to assess risks of dying from non-cancer diseases (respiratory, urinary, cerebrovascular, circulatory and digestive diseases). Occupational exposures to rubber dust, rubber fumes, N-nitrosamines were derived based on a population-specific quantitative job-exposure matrix which in-turn was based on measurements in the EU-EXASRUB database.ResultsExposure–response associations of increased risk with increasing exposure were found for N-nitrosomorpholine with mortality from circulatory diseases (subdistribution hazard ratio (SHR) 1.17; 95% CI 1.12 to 1.23), ischaemic heart disease (IHD) (SHR 1.19; 95% CI 1.13 to 1.26), cerebrovascular disease (SHR 1.19; 95% CI 1.07 to 1.32) and exposures to N-nitrosodimethylamine with respiratory disease mortality (SHR 1.41; 95% CI 1.30 to 1.53). Increased risks for mortality from circulatory disease, IHD and digestive diseases were found with higher levels of exposures to rubber dust, rubber fumes and N-nitrosamines sum, without an exposure-dependent manner. No associations were observed between rubber dust, rubber fumes and N-nitrosamines exposures with mortality from asthma, urinary disease, bronchitis, emphysema, liver disease and some digestive diseases.ConclusionsIn a cohort of rubber factory workers with 49 years of follow-up, increased risk for mortality from circulatory, cerebrovascular, respiratory and digestive diseases were found to be associated with cumulative occupational exposures to specific agents.

ObjectiveLinear and non-linear dose–response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers.MethodsRate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease.ResultsThere was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null.ConclusionsNon-linear dose–response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality.

ObjectivesExcess risk of suicide has been reported among workers in agriculture, fishery, forestry and hunting (AFFH). However, there is still uncertainty in the quantification of the risk and in the contribution of work-related factors. We aimed to quantify the suicide mortality risk among these workers in Italy.MethodsWe carried out a historical cohort study based on record linkage between the 2011 Italian census and the mortality archives for years 2012–2017. The mortality rate ratio (MRR) was used as a measure of risk. MRR was estimated through quasi-Poisson regression models using workers in other sectors as reference category. Models were adjusted for age, citizenship, marital status, area of residence, education, employment status and hours worked per week.ResultsThe cohort included 1 004 655 workers employed in the AFFH sector and 15 269 181 workers in other sectors. During the 6-year follow-up, 559 deaths from suicide (500 men and 59 women) occurred among AFFH workers and 5917 (4935 men and 982 women) among workers in other sectors. The MRR for suicide was 1.36 (95% CI 1.19 to 1.55) among men and 1.18 (95% CI 0.87 to 1.60) among women. The excess risk was remarkably high for casual and fixed-term contract workers (3.01, 95% CI 1.50 to 6.04).ConclusionsMale workers in AFFH are at high risk of suicide mortality, and casual and fixed-term contract workers are at exceedingly high risk. Our study also suggests a higher risk among single, highly educated and long-hours workers. Female workers in AFFH do not have an appreciably increased risk.

ObjectivesTo determine cancer mortality compared with the general population and to examine dose-response relationships between cumulative occupational radiation dose and specific cancer outcomes in the German aircrew cohort.MethodsFor a cohort of 26 846 aircrew personnel, standardised mortality ratios (SMR) were calculated. Dose-response analyses were carried out using Poisson regression to assess dose-related cancer risks for the period 1960–2014. Exposure assessment comprises recently available dose register data for all cohort members and newly estimated retrospective cabin crew doses for 1960–2003.ResultsSMR for all-cause, specific cancer groups and most individual cancers were reduced in all aircrew groups. The only increases were seen for brain cancer in pilots (n=23, SMR 2.01, 95% CI 1.15 to 3.28) and for malignant melanoma (n=10, SMR 1.88, 95% CI 0.78 to 3.85). Breast cancer mortality among female cabin crew was similar to the general population (n=71, SMR 1.06, 95% CI 0.77 to 1.44). Overall median cumulative effective dose was 34.2 mSv (max: 116 mSv) for 1960–2014. No dose-response associations were seen in any of the models. For brain cancer, relative risks were elevated across dose categories. An indicative negative trend with increasing dose category was seen for large intestine cancer in female cabin crew (n=23).ConclusionsThere was no evidence for significant dose-response patterns for the considered cancer types. Interpretation of results remains difficult as cumulative dose is closely related to age. Future work should focus on investigating radiation jointly with other risk factors that may contribute to risks for specific cancers among aircrew.

ObjectivesTitanium dioxide (TiO2) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO2 carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO2 workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO2 exposure, co-exposures or smoking can explain this increase.MethodsWe reanalysed the data of 833 French male workers (follow-up period 1968–1997) and used multiple imputation to complete their smoking status. We considered respirable TiO2 dust as primary exposure of interest, estimated as continuous cumulative (mg/m3-year) and annual average (mg/m3) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m3 (the German and American occupational exposure limits, respectively). For each exposure metric, we estimated HRs and associated 95% CIs, using Cox regression models adjusted for calendar period, exposure duration and smoking.ResultsThe fully adjusted model yielded a HR=3.7 (95% CI=0.79 to 17.95) for TiO2-exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m3 as annual average concentration. Employment duration was negatively related with lung cancer mortality, therefore cumulative exposure had a small effect on mortality (HR=1.03 (95% CI=0.99 to 1.08) per mg/m3-year).ConclusionThis study suggests a positive relationship between TiO2 exposure and lung cancer mortality in TiO2 workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO2 carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches.