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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.

Whether high blood eosinophils are associated with chronic obstructive pulmonary disease (COPD) exacerbations among individuals with COPD in the general population is largely unknown. To test the hypothesis that high blood eosinophils predict COPD exacerbations. Among 81,668 individuals in the Copenhagen General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment with systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk in a subgroup of 203 individuals with clinical COPD, defined as participants with a smoking history of at least 10 pack-years, FEV1 less than 70% of predicted value, and at least one moderate or severe exacerbation in the year before baseline. During a median of 3.3 years of follow-up (range, 0.03-8.1), 1,439 severe and 2,864 moderate COPD exacerbations were recorded. Among all participants with COPD, blood eosinophils above versus below 0.34 × 10(9) cells per liter had multivariable-adjusted incidence rate ratios of 1.76 (95% confidence interval, 1.56-1.99) for severe exacerbations and 1.15 (1.05-1.27) for moderate exacerbations. Corresponding values in those with clinical COPD were 3.21 (2.49-4.14) and 1.69 (1.40-2.04). In contrast, using a cutpoint of 2% for blood eosinophils, the risk of exacerbations was increased for severe exacerbations only among individuals with clinical COPD and not in individuals in the broader population. Among individuals with COPD in the general population, increased blood eosinophil levels above 0.34 × 10(9) cells per liter were associated with a 1.76-fold increased risk of severe exacerbations.

Abstract Rationale Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive. Objectives In this study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults. Methods Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participant’s residence from a hierarchical Bayesian space–time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 μm [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates. Measurements and Main Results In single-pollutant models, we observed significant positive associations between O3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O3 and all-cause (hazard ratio [HR] per 10 ppb, 1.02; 95% confidence interval [CI], 1.01–1.04), circulatory (HR, 1.03; 95% CI, 1.01–1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08–1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models. Conclusions Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations.

Background The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life’s Essential 8 . We examined the association of total and individual CVH metrics according to Life’s Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in  life. Methods Data were from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0–49 (low level), 50–74 (intermediate level), and 75–100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose–response analysis. The main outcomes included all-cause and CVD-specific mortality. Results A total of 19,951 US adults aged 30–79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51–0.71) and 58% (adjusted HR 0.42, 95% CI 0.32–0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46–0.83) and 0.36 (0.21–0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score < 75 points) CVH scores were 33.4% for all-cause mortality and 42.9% for CVD-specific mortality. Among all 8 individual CVH metrics, physical activity, nicotine exposure, and diet accounted for a large proportion of the population-attributable risks for all-cause mortality, whereas physical activity, blood pressure, and blood glucose accounted for a large proportion of CVD-specific mortality. There were approximately linear dose–response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality. Conclusions Achieving a higher CVH score according to the new Life’s Essential 8 was associated with a reduced risk of all-cause and CVD-specific mortality. Public health and healthcare efforts targeting the promotion of higher CVH scores could provide considerable benefits to reduce the mortality burden later in life.

Background There is limited evidence on sarcopenia in Asian populations. This study aimed to clarify the prevalence, associated factors, and the magnitude of association with mortality and incident disability for sarcopenia and combinations of its components among Japanese community‐dwelling older adults. Methods We conducted a 5.8 year prospective study of 1851 Japanese residents aged 65 years or older (50.5% women; mean age 72.0 ± 5.9) who participated in health check‐ups. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Appendicular lean mass index (ALMI) was measured using direct segmental multi‐frequency bioelectrical impedance analysis. A Cox proportional hazards regression model was used to identify associations of sarcopenia and the combinations of its components with all‐cause mortality and incident disability. Results The prevalence of sarcopenia was 11.5% (105/917) in men and 16.7% (156/934) in women. Significant sarcopenia‐related factors other than ageing were hypoalbuminaemia, cognitive impairment, low activity, and recent hospitalization (all P‐values <0.05) among men and cognitive impairment (P = 0.004) and depressed mood (P < 0.001) among women. Individuals with sarcopenia had higher risks of mortality [hazard ratios (95% confidence interval): 2.0 (1.2–3.5) in men and 2.3 (1.1–4.9) in women] and incident disability [1.6 (1.0–2.7) in men and 1.7 (1.1–2.7) in women]. Compared with the individuals without any sarcopenia components, those having low grip strength and/or slow gait speed without low ALMI tended to have an increased risk of disability [1.4 (1.0–2.0), P = 0.087], but not mortality [1.3 (0.8–2.2)]. We did not find increased risks of these outcomes in participants having low ALMI in the absence of low grip strength and slow gait speed [1.2 (0.8–1.9) for mortality and 0.9 (0.6–1.3) for incident disability]. Conclusions Japanese older men and women meeting Asian criteria of sarcopenia had increased risks of all‐cause mortality and disability. There were no significant increased risks of death or incident disability for both participants with muscle weakness and/or low performance without low muscle mass and those with low muscle mass with neither muscle weakness nor low performance. Further studies are needed to examine the interaction between muscle loss, muscle weakness, and low performance for adverse health‐related outcomes.

AbstractObjectiveTo evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study.DesignProspective cohort study.SettingPURE study in 21 countries.Participants148 858 participants with median follow-up of 9.5 years.ExposuresCountry specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice.Main outcome measureComposite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre.ResultsAnalyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes.ConclusionHigh intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.

Purpose A growing body of evidence shows that consumption of ultra-processed foods (UPF) is associated with a higher risk of cardiometabolic diseases, which, in turn, have been linked to depression. This suggests that UPF might also be associated with depression, which is among the global leading causes of disability and disease. We prospectively evaluated the relationship between UPF consumption and the risk of depression in a Mediterranean cohort. Methods We included 14,907 Spanish university graduates [mean (SD) age: 36.7 year (11.7)] initially free of depression who were followed up for a median of 10.3 years. Consumption of UPF (industrial formulations made mostly or entirely from substances derived from foods and additives, with little, if any, intact food), as defined by the NOVA food classification system, was assessed at baseline through a validated semi-quantitative 136-item food-frequency questionnaire. Participants were classified as incident cases of depression if they reported a medical diagnosis of depression or the habitual use of antidepressant medication in at least one of the follow-up assessments conducted after the first 2 years of follow-up. Cox regression models were used to assess the relationship between UPF consumption and depression incidence. Results A total of 774 incident cases of depression were identified during follow-up. Participants in the highest quartile of UPF consumption had a higher risk of developing depression [HR (95% CI) 1.33 (1.07–1.64); p trend = 0.004] than those in the lowest quartile after adjusting for potential confounders. Conclusions In a prospective cohort of Spanish university graduates, we found a positive association between UPF consumption and the risk of depression that was strongest among participants with low levels of physical activity.

Upper gastrointestinal endoscopy for gastric cancer screening has been implemented in Japan. However, its effectiveness for gastric cancer prevention has not been fully studied. We aimed to investigate the effectiveness of endoscopic screening to reduce mortality from gastric cancer. In a large prospective population‐based cohort study including 80,272 participants, we compared the risk of mortality and incidence of gastric cancer among participants who underwent endoscopic or radiographic screening compared with those who did not undergo any screening using multivariable Cox proportional hazards models. In the 1,023,364 person‐year observation period (median; 13.0 years), 1977 cases of gastric cancer were diagnosed, and 783 patients with gastric cancer died. In the endoscopic screening group, the mortality from gastric cancer and incidence of advanced gastric cancer were reduced by 61% (hazard ratio [HR] = 0.39 [95% CI: 0.30–0.51]) and 22% (HR = 0.78 [95% CI: 0.67–0.90]), respectively. The radiographic screening reduced the mortality from gastric cancer (HR = 0.63 [95% CI: 0.54–0.73]), but its effectiveness was lower than that of endoscopic screening. In conclusion, endoscopic screening reduced the incidence of advanced gastric cancer and mortality from gastric cancer in the Japanese population. In this Japanese prospective population‐based cohort study, endoscopic screening reduced the incidence of advanced gastric cancer by 22% and mortality from gastric cancer by 61% compared with no screening. The effectiveness of endoscopic screening on reducing gastric cancer mortality was greater than that of radiographic screening. The results provide a rationale for promoting endoscopic screening for gastric cancer, which has a high mortality rate and significant public health impact in Japan.

Background Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments. Methods This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016–September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study. Results A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%. Conclusions The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.

Background There is limited prospective evidence on possible differences in fracture risks between vegetarians, vegans, and non-vegetarians. We aimed to study this in a prospective cohort with a large proportion of non-meat eaters. Methods In EPIC-Oxford, dietary information was collected at baseline (1993–2001) and at follow-up (≈ 2010). Participants were categorised into four diet groups at both time points (with 29,380 meat eaters, 8037 fish eaters, 15,499 vegetarians, and 1982 vegans at baseline in analyses of total fractures). Outcomes were identified through linkage to hospital records or death certificates until mid-2016. Using multivariable Cox regression, we estimated the risks of total ( n  = 3941) and site-specific fractures (arm, n  = 566; wrist, n  = 889; hip, n  = 945; leg, n  = 366; ankle, n  = 520; other main sites, i.e. clavicle, rib, and vertebra, n  = 467) by diet group over an average of 17.6 years of follow-up. Results Compared with meat eaters and after adjustment for socio-economic factors, lifestyle confounders, and body mass index (BMI), the risks of hip fracture were higher in fish eaters (hazard ratio 1.26; 95% CI 1.02–1.54), vegetarians (1.25; 1.04–1.50), and vegans (2.31; 1.66–3.22), equivalent to rate differences of 2.9 (0.6–5.7), 2.9 (0.9–5.2), and 14.9 (7.9–24.5) more cases for every 1000 people over 10 years, respectively. The vegans also had higher risks of total (1.43; 1.20–1.70), leg (2.05; 1.23–3.41), and other main site fractures (1.59; 1.02–2.50) than meat eaters. Overall, the significant associations appeared to be stronger without adjustment for BMI and were slightly attenuated but remained significant with additional adjustment for dietary calcium and/or total protein. No significant differences were observed in risks of wrist or ankle fractures by diet group with or without BMI adjustment, nor for arm fractures after BMI adjustment. Conclusions Non-meat eaters, especially vegans, had higher risks of either total or some site-specific fractures, particularly hip fractures. This is the first prospective study of diet group with both total and multiple specific fracture sites in vegetarians and vegans, and the findings suggest that bone health in vegans requires further research.