Search

Objectives: We performed a systematic review and meta-analysis on long-term exposure to nitrogen dioxide (NO 2 ) and ozone (O 3 ) with mortality, to expand evidence that informed 2021 the WHO Air Quality Guidelines and guide the Health Risks of Air Pollution in Europe project., Methods: We included cohorts investigating NO 2 and O 3 mortality from all-causes, respiratory diseases, chronic obstructive pulmonary disease (COPD), acute lower respiratory infections (ALRI); and NO 2 mortality from circulatory, ischemic heart, cerebrovascular diseases and lung cancer. We pooled estimates by random-effects models and investigated heterogeneity. We assessed the certainty of the evidence using the Grading of Recommendations Assessment Development approach and Evaluation (GRADE)., Results: We selected 83 studies for NO 2 and 26 for O 3 for the meta-analysis. NO 2 was associated with all outcomes, except for cerebrovascular mortality. O 3 was associated with respiratory mortality following annual exposure. There was high heterogeneity, partly explained by region and pollutant levels. Certainty was high for NO 2 with COPD and ALRI, and annual O 3 with respiratory mortality., Conclusion: An increasing body of evidence, with new results from countrywide areas and the Western Pacific, supports certainty, including new outcomes., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © World Health Organization 2024. Licensee Frontiers Media SA and Stiftung Swiss School of Public Health plus.)

Objectives: Current variations in asthma prevalence and clinical characteristics suggest that lifestyle choices including dietary habits, may affect the pathogenesis and/or clinical expression of the disease. The purpose of this study is to evaluate the association between adherence to Mediterranean diet (MD) and asthma control, considering disease severity., Methods: Adherence to MD was assessed through a questionnaire, the MD Adherence Screener (MEDAS), previously validated in Mediterranean populations. Each participant received a score ranging from 0 to 14. A score higher than 10 indicates high MD adherence. The level of asthma control was assessed by the Asthma Control Test and two groups were formed (controlled vs. partly controlled/uncontrolled)., Results: The study sample included 105 participants (34% males). About 45% of participants were severe asthmatics. Adherence to MD was associated with 14% higher, though not statistically significant, probability of controlled asthma in the overall study sample (OR = 1.14; 95% CI = 0.46-2.81) and 60% higher probability of controlled asthma among severe asthmatics (OR = 1.60, 95% CI = 0.46-5.59)., Conclusions: These results indicate a possible association between adherence to MD and asthma control, but findings are restricted by the study's small sample size which does not allow asserting the inference.

Objectives: For the development of the 2021 global air quality guidelines, the World Health Organization (WHO) commissioned a series of systematic reviews and meta-analyses to assess the association between exposure to air pollution and all-cause and cause-specific mortality. One of these reviews, which we aim to update, focused on the effects of long-term exposure to PM 2.5 and PM 10 on all-cause and cause-specific mortality., Methods: The protocol for this study was registered in PROSPERO (CRD42023425327). We searched the PubMed and Embase databases for studies published between September 2018 and May 2023. Study-specific effects were pooled using random-effects models., Results: We included 106 studies in the meta-analysis, 46 studies from the previous review and 60 from this update. All exposure-outcome pairs analysed showed positive and significant associations, except for PM 10 and cerebrovascular mortality. The certainty of the evidence was rated as high for the majority of exposure-outcome pairs., Conclusion: We included a large number of new cohorts, and provided new concentration-response functions that will inform WHO advice on the use of this information for air pollution health risk assessments., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © World Health Organization 2024. Licensee Frontiers Media SA and Stiftung Swiss School of Public Health plus.)

Background: We evaluated the independent and joint effects of air pollution, land/built environment characteristics, and ambient temperature on all-cause mortality as part of the EXPANSE project., Methods: We collected data from six administrative cohorts covering Catalonia, Greece, the Netherlands, Rome, Sweden, and Switzerland and three traditional cohorts in Sweden, the Netherlands, and Germany. Participants were linked to spatial exposure estimates derived from hybrid land use regression models and satellite data for: air pollution [fine particulate matter (PM 2.5 ), nitrogen dioxide (NO₂), black carbon (BC), warm season ozone (O 3 )], land/built environment [normalized difference vegetation index (NDVI), distance to water, impervious surfaces], and ambient temperature (the mean and standard deviation of warm and cool season temperature). We applied Cox proportional hazard models accounting for several cohort-specific individual and area-level variables. We evaluated the associations through single and multiexposure models, and interactions between exposures. The joint effects were estimated using the cumulative risk index (CRI). Cohort-specific hazard ratios (HR) were combined using random-effects meta-analyses., Results: We observed over 3.1 million deaths out of approximately 204 million person-years. In administrative cohorts, increased exposure to PM 2.5 , NO 2 , and BC was significantly associated with all-cause mortality (pooled HRs: 1.054, 1.033, and 1.032, respectively). We observed an adverse effect of increased impervious surface and mean season-specific temperature, and a protective effect of increased O 3 , NDVI, distance to water, and temperature variation on all-cause mortality. The effects of PM 2.5 were higher in areas with lower (10th percentile) compared to higher (90th percentile) NDVI levels [pooled HRs: 1.054 (95% confidence interval (CI) 1.030-1.079) vs. 1.038 (95% CI 0.964-1.118)]. A similar pattern was observed for NO 2 . The CRI of air pollutants (PM 2.5 or NO 2 ) plus NDVI and mean warm season temperature resulted in a stronger effect compared to single-exposure HRs: [PM 2.5 pooled HR: 1.061 (95% CI 1.021-1.102); NO 2 pooled HR: 1.041 (95% CI 1.025-1.057)]. Non-significant effects of similar patterns were observed in traditional cohorts., Discussion: The findings of our study not only support the independent effects of long-term exposure to air pollution and greenness, but also highlight the increased effect when interplaying with other environmental exposures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer-review process and the final decision., (© 2024 Dimakopoulou, Nobile, de Bont, Wolf, Vienneau, Ibi, Coloma, Pickford, Åström, Sommar, Kasdagli, Souliotis, Tsolakidis, Tonne, Melén, Ljungman, de Hoogh, Vermeulen, Vlaanderen, Katsouyanni, Stafoggia and Samoli.)

Objective: Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral anti-osteoporotic drugs in randomized controlled trials (RCT) can experience adverse events leading to dropout, implying that nocebo contributes to treatment discontinuation for these drugs. In this study we aim to investigate the nocebo effect of subcutaneous anti-osteoporotic drugs with a higher compliance rate than orally administered drugs., Study Design: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for double-blind trials investigating subcutaneous anti-osteoporotic drugs for osteoporosis (namely, denosumab, teriparatide, abaloparatide and romosozumab) published up to May 2023., Main Outcome Measure: Dropouts due to reported adverse events in the placebo arms ("nocebo dropouts")., Results: Data from 17 trials were extracted. Among 10,529 placebo-treated patients the pooled nocebo-dropout percentage was 3 % for denosumab (average: 0.03; 95 % CI: 0.01-0.05), 1 % for romosozumab (average: 0.01; 95 % CI: 0.00-0.03) and 6 % for teriparatide and abaloparatide (average: 0.06; 95 % CI: 0.05-0.07). Nocebo-dropouts were significantly higher in men than women (6 % vs. 3 %, respectively, p = 0.012), in older (mean age >68 years) than in younger patients (5 % vs. 1 %, respectively, p = 0.017) and in those with more severe osteoporosis (based on the percentage of participants with prior fragility-related fractures in the study cohort) compared with patients with no prior fracture history (4 % vs. 1 %, respectively, p = 0.046)., Conclusion: Nocebo responses may contribute to treatment discontinuation with subcutaneous anti-osteoporotic drugs in clinical practice. Higher nocebo-related dropout rates in the higher-risk RCT population (older patients, males, those with prior fractures) show that nocebo mechanisms have the potential to hinder therapeutic efforts to specific populations who would benefit most. Prospero registration number CRD42020212843., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest. RCTs, randomized controlled trials; Fx, fractures., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) is a chronic demyelinating inflammatory disorder of the central nervous system that may affect respiratory system at the later stages of the disease. The aim of our study was to evaluate respiratory function and cardiopulmonary exercise testing in ambulatory without aid people with MS (pwMS), and to investigate quality of life parameters and fatigue in this population., Methods: 25 pwMS and 16 healthy controls were included in this study. Pulmonary function tests were performed and were followed by proper cardiopulmonary exercise testing with the use of treadmill. Quality of life assessment was done with SF-36 questionnaire., Results: The mean age of the patient group was 38.4 ± 8.2 years. Spirometric values were within normal limits, and so did lung diffusion capacity, while maximal voluntary ventilation was reduced. In cardiopulmonary exercise testing the patient group showed impairment compared to control group. The statistically significant lower parameters were V'O 2 peak, V'CO 2 peak, RER, V'O 2 /kg peak, V'CO 2 /kg peak, oxygen pulse peak and V'E/V'CO 2 slope. Moreover, there was a negative and statistically significant correlation between CPET values and BMI and MFIS, while there was a positive and statistically significant correlation with quality of life, evaluated by SF-36., Conclusion: Our study showed that the main cardiopulmonary exercise testing parameters were affected in ambulatory pwMS, even without evidence of respiratory symptoms. Therefore, these people should be evaluated for pulmonary function compromise., Competing Interests: Declaration of Competing Interest All the other authors have nothing to declare., (Copyright © 2023. Published by Elsevier B.V.)

We assessed the quality of food-related OpenStreetMap (OSM) data in urban areas of five European countries. We calculated agreement statistics between point-of-interests (POIs) from OSM and from Google Street View (GSV) in five European regions. We furthermore assessed correlations between exposure measures (distance and counts) from OSM data and administrative data from local data sources on food environment data in three European countries. Agreement between POI data in OSM compared to GSV was poor, but correlations were moderate to high between exposures from OSM and local data sources. OSM data downloaded in 2020 seems to be an acceptable source of data for generating count-based food exposure measures for research in selected European regions., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Νon-alcoholic fatty liver disease (NAFLD) is a common cause of end-stage liver disease in developed countries. Oxidative stress plays a key role during the course of the disease and vitamin E supplementation has shown to be beneficial due to its antioxidative properties. We aim to investigate the effect of vitamin E supplementation on serum aminotransferase levels in patients with NAFLD. Three electronic databases (MEDLINE, CENTRAL, and Embase) were reviewed for randomized trials that tested vitamin E supplementation versus placebo or no intervention in patients with NAFLD, published until April 2023. A total of 794 patients from 12 randomized trials were included in this meta-analysis. Notwithstanding the studies' heterogeneity and moderate internal validity in certain cases, among studies testing vitamin E supplementation at 400 IU/day and above, the values of alanine aminotransferase (ALT) were reduced compared with placebo or no intervention [ALT Mean Difference (MD) = -6.99 IU/L, 95% CI (-9.63, -4.35), for studies conducted in Asian countries and MD = -9.57 IU/L, 95% CI (-12.20, -6.95) in non-Asian countries]. Regarding aspartate aminotransferase (AST), patients in the experimental group experienced a reduction in serum levels, though smaller in absolute values [AST MD = -4.65 IU/L, 95% CI (-7.44, -1.86) in studies conducted in Asian populations] and of lower precision in non-Asian studies [MD = -5.60 IU/L, 95% CI (-11.48, 0.28)].

Background: A growing body of evidence suggests that exposure to natural environments, such as green space, may have a beneficial role in health. However, there is limited evidence regarding the effects of exposure to blue spaces and mortality. We investigated the association of exposure to blue spaces with natural and cause-specific mortality in Greece using an ecological study design METHODS: Mortality and socioeconomic data were obtained from 1,035 municipal units (MUs) from the 2011 census data. To define exposure to "blue" we used a rate of the land cover categories related to blue space from the COoRdination and INformation on the Environmental (CORINE) 2012 map per 10,000 persons in the municipal unit. We further assessed the exposure to blue space in the MUs that are located in the coastline of Greece using the distance to the coast as a proxy for proximity to blue space. the Annual PM 2.5 , NO 2 , BC and O 3 concentrations for 2010 were predicted by land use regression models while the normalized difference vegetation index was used to assess greenness. We applied single and two exposure Poisson regression models accounting for spatial autocorrelation and adjusting for unemployment and lung cancer mortality rates, percentages of the population aged 25-64 with upper secondary or tertiary education attainment and of those born in Greece, and urbanicity. The analysis was conducted for the whole country and separately by varying geographical definitions., Results: An interquartile range (IQR) increase of blue space per 10,000 persons was associated with decreased risk in natural mortality (Relative Risk (RR): 0.98 (95% confidence interval (CI): 0.98, 0.99), as well as in mortality due to cardiovascular causes, respiratory causes and diseases of the nervous system 0.98 (95% CI: 0.97, 0.99); 0.97 (95% CI: 0.95, 0.99); 0.94 (95% CI: 0.88, 1.00) respectively). We estimated protective associations for ischemic heart disease (IHD) mortality (RR = 0.98, 95% CI: 0.97, 1.00 per IQR); COPD mortality (RR = 0.97, 95% CI: 0.93, 1.00 per IQR) and mortality from cerebrovascular disease (RR = 0.97 (95% CI: 0.96, 0.99 per IQR). We estimated protective associations for the distance from the coast and mortality from the diseases of the nervous system (RR = 0.75, 95% CI: 0.61, 0.92, ≤1 km from the coast versus >1 km). Our results were stronger for inhabitants of the islands, the coastline and in the rural areas of Greece while the estimates were robust to co-exposure adjustment., Conclusions: We estimated statistically significant protective effects of exposure to blue space on mortality from natural, cardiovascular and respiratory causes, diseases of the nervous system, cerebrovascular and ischemic heart disease for in Greece with higher estimates in the coastline and the islands. Further research is needed to elaborate our findings., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Dropout from placebo arms in randomized-controlled trials is a surrogate for nocebo responses, resulting from patients' negative expectations to treatment. Among 16,460 placebo-treated patients in oral anti-osteoporotic drug trials, nocebo dropouts were 8% on average, being higher in older patients. This implies that nocebo may contribute to the osteoporosis treatment gap in clinical practice., Purpose: Osteoporosis is a common disease requiring long-term treatment. Despite the availability of effective anti-osteoporotic drugs, adherence to treatment is low. Nocebo, a behavior mostly related to the negative expectations to a certain treatment, decreases adherence and negatively affects treatment outcomes and health-related care costs in chronic diseases. Since in double-blind placebo-controlled randomized trials any unfavorable outcome leading to discontinuation in placebo arms is considered as nocebo, we aimed to investigate the size of nocebo response in patients participating in osteoporosis trials., Methods: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for dropouts due to reported adverse events in the placebo arms (nocebo dropouts) in all double-blind trials investigating anti-osteoporotic drugs published between January 1993 and March 2022. Only data on bisphosphonates and selective estrogen receptor modulators (SERMs) were analyzed (Prospero registration number CRD42020212843)., Results: Data from 44 trials were extracted. In 16,460 placebo-treated patients, the pooled nocebo-dropout was 8% both for bisphosphonates (average: 0.08; range 0.01-0.27; 95%CI 0.06-0.10) and SERMs (average: 0.08; range 0.03-0.15; 95%CI 0.05-0.13). Nocebo-dropouts were higher in bisphosphonate trials enrolling individuals ≥ 65 years (11%) (n = 18) compared to trials enrolling younger individuals (6%) (n = 18) (average: 0.11; 95%CI 0.08-0.13 vs. average: 0.06; 95%CI 0.05-0.08, respectively, p = 0.001). Participants' sex, dosing-intervals, publication year, or severity of osteoporosis had no impact on the nocebo-dropouts., Conclusion: Almost 1 in 10 osteoporosis patients receiving placebo in trials of bisphosphonates and SERMs experiences AEs leading to dropout, implying that nocebo contributes to treatment-discontinuation in clinical practice. Efforts to identify and minimize nocebo, especially in older patients, are warranted., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Aims: To summarize the evidence on the association between the intake of legumes and the risk of cardiovascular disease (CVD) overall, coronary heart disease (CHD) and stroke, and to identify optimal intake levels for reduced disease risk through a systematic review and dose-response meta-analysis., Data Synthesis: We have systematically searched PubMed, Scopus and Web of Science up to March, 2022 for the retrieval of intervention and observational studies (PROSPERO Reg. number: CRD42021247565). Pooled relative risks (RRs) comparing extreme categories of intake were computed using random-effects models. One-stage dose-response meta-analyses were also performed using random-effects models. 22 831 articles were screened resulting in 26 eligible observational studies (21 prospective cohort and 5 case-control studies). When comparing extreme categories of intake, the consumption of legumes was inversely associated with CVD (n = 25: RR = 0.94; 95%CI:0.89,0.99) and CHD (n = 16: RR = 0.90; 95%CI:0.85,0.96), but not with stroke (n = 9: RR = 1.00; 95%CI:0.93,1.08). We further found evidence for an inverse dose-response association with CHD, increasing in magnitude up to an intake of 400 g/week, after which the benefit seems to level-off., Conclusions: The intake of legumes was associated with a reduced risk of CVD and CHD, but not with stroke, among individuals with the highest consumption levels. An intake level of 400 g/week seemed to provide the optimal cardiovascular benefit. Further research is needed to better understand the role of legumes in stroke subtypes., Competing Interests: Declaration of competing interest No potential conflicts of interest to disclose., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Diabetic peripheral neuropathy (DPN) is present in 20-50% of cases with diabetes. The pathophysiology of DPN is not yet clear regarding hypertension (HTN). The aim of this study was to assess the association between the stages of DPN and HTN in a Greek population with diabetes. We examined 102 adults for diabetic neuropathy (DPN) from November 2020 to December 2021, using the Toronto Clinical Neuropathy Scale System (TCNSS) to categorize them into two groups (no/mild DPN versus medium/severe DPN). Ambulatory blood pressure monitoring was performed to evaluate their hypertensive status. Univariate and multivariate logistic regression analyses were performed to assess the association between the stage of DPN and HTN. The multivariate analysis, considering sex, age, and dipping status, did not show statistically significant associations between stages of HTN and DPN. However, in contrast to dippers, non-dippers had an almost four-times higher risk of developing medium-to-severe DPN (odds ratio (OR) 3.93; 95% confidence interval (CI) [1.33-11.64]); females, in contrast to males, had a 65% lower risk of developing moderate/severe DPN (OR 0.35; 95%CI [0.14-0.92]). In conclusion, our findings showed no statistically significant associations between DPN and HTN; however, dipping status, hyperglycemia, and female sex were shown to play a role in the pathophysiology of DPN.

Context: Randomized controlled trials (RCTs) testing supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have failed to provide evidence supporting a suggested inverse association between fish intake and dementia risk., Objective: Dose-response analyses were conducted to evaluate associations between fish intake, all-cause dementia or Alzheimer's Disease (AD), and the effect of EPA/DHA supplementation on cognitive performance., Data Sources: PubMed, Scopus and Web of Science databases were searched for original research evaluating either associations between fish intake and dementia or AD, or the impact of EPA and/or DHA supplementation on the risk of cognitive decline., Data Extraction: Data were collected on study characteristics and methods; number of cases/deaths (for observational studies); categories of exposure; model covariates; risk estimates from the most-adjusted model; type and dosage of supplementation (from RCTs); fatty acid levels in blood; and differences in cognition test results before and after supplementation. Risk of bias was assessed through the ROBINS-E and RoB2.0 tools for observational and experimental studies, respectively., Data Analysis: Weighted mixed-effects models were applied, allowing for the inclusion of studies with 2 levels of exposure. Based on findings with low/moderate risk of bias, fish intake of up to 2 portions (250 g) per week was associated with a 10% reduction (95% confidence interval [CI]: 0.79, 1.02, Ν = 5) in all-cause dementia and a 30% reduction (95% CI: 0.54, 0.89, Ν = 3) in AD risk. Changes in EPA and DHA body status had a positive impact on participants' executive functions, but not on their overall cognitive performance., Conclusion: The protection offered by fish intake against cognitive decline levels off at intakes higher than 2 portions/week and likely relates to the impact of EPA and DHA on the individual's executive functions, although there remain questions about the mechanisms linking the short- and long-term effects., Systematic Review Registration: PROSPERO registration no. CRD42019139528., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Long-term exposure to air pollution has been associated with increased natural-cause mortality, but the evidence on diagnoses-specific mortality outcomes is limited. Few studies have examined the potential synergistic effects of exposure to pollutants and greenness. We investigated the association between exposure to air pollution and greenness with nervous system related mortality, cardiometabolic and chronic obstructive pulmonary diseases (COPD) mortality in Greece, using an ecological study design. We collected socioeconomic and mortality data for 1035 municipal units from the 2011 Census. Annual PM 2.5 , NO 2 , BC and O 3 concentrations for 2010 were predicted at 100 × 100 m grids by hybrid land use regression models. The normalized difference vegetation index (NDVI) was used for greenness. We applied single and two-exposure Poisson regression models on standardized mortality rates accounting for spatial autocorrelation. We assessed interactions between pollutants and greenness. An interquartile range increase in PM 2.5 , NO 2 and BC was associated with increased risk in mortality from diseases of the nervous system (relative risk (RR): 1.14, 95% confidence interval (CI): 1.01, 1.28); 1.03 (95% CI: 0.99, 1.07); 1.05 (95% CI: 1.00, 1.10) respectively) and from cerebrovascular disease (RR: 1.14, 95% CI: 1.10, 1.18); 1.02 (95% CI: 1.01, 1.04); 1.02 (95% CI: 1.00, 1.04) respectively). PM 2.5 was associated with ischemic heart disease mortality (RR: 1.05, 95% CI: 1.01, 1.10). We estimated inverse associations for all outcomes with O 3 and for mortality from diseases of the nervous system or COPD with greenness. Estimates were mostly robust to co-exposure adjustment. Interactions were identified between NDVI and O 3 or PM 2.5 on mortality from the diseases of the nervous system, with higher effect estimates in greener areas. Our findings support the adverse effects of air pollution and the beneficial role of greenness on cardiovascular and nervous system related mortality. Further research is needed on diabetes mellitus., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Epidemiological studies have documented the adverse effects of long-term exposure to fine particulate matter (PM 2.5 ) on health, while there has been less research on the effects of nitrogen dioxide (NO 2 ), black carbon (BC) and especially ozone (O 3 ). Furthermore, there is limited evidence for the synergistic effects of exposure to pollutants and greenness. We investigated the association of long-term exposure to air pollution and greenness with natural-cause, cardiovascular and respiratory mortality in Greece using an ecological study design., Methods: Mortality and socioeconomic data were obtained from 1035 municipal units from the 2011 census data. Annual average PM 2.5 , NO 2 , BC and O 3 concentrations for 2010 were derived from 100 × 100 m surfaces predicted by hybrid LUR models. The normalized difference vegetation index was used to assess greenness. We applied Poisson regression models on standardized mortality rates adjusted for socioeconomic indicators and lung cancer rates, accounting for spatial autocorrelation. The analysis was conducted initially for the whole country and then separately for urban and rural areas. We assessed interactions between pollutants and greenness and applied two-exposure models., Results: An interquartile range (IQR) increase in PM 2.5 , NO 2 and BC was associated with increases in natural-cause mortality (Relative Risk (RR) 1.09, 95% confidence interval (CI): 1.08, 1.11; RR 1.03 (95% CI: 1.03, 1.04) and RR 1.02 (95% CI: 1.02, 1.03), respectively), while PM 2.5 and NO 2 were also associated with cause-specific mortality. Greenness was associated with lower natural-cause (RR 0.95, 95% CI: 0.94, 0.96 per IQR) and cause-specific mortality. For all outcomes we estimated a protective association with O 3 (natural-cause mortality RR 0.79, 95% CI: 0.76, 0.82 per IQR). All associations were stronger in urban areas. We estimated negative statistically significant interactions between air pollution and greenness for respiratory morality and positive ones for cardiovascular mortality. Estimates were mostly robust to co-exposure adjustment., Conclusions: Our findings support associations of air pollution and greenness with mortality, both in urban and rural areas of Greece. Further research is needed to elaborate on the synergies in cause-specific mortality. Our results on the interactions between pollutants and greenness may imply differential biological mechanisms for cause-specific mortality and warrant further investigation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results., Objective: To investigate the shape of the relation between cadmium exposure and breast cancer incidence and mortality in cohort studies., Data Sources: Following a literature search through April 14, 2020, we carried out a systematic review and dose-response meta-analysis to investigate the shape of the relation between cadmium exposure (assessed either through diet or urine excretion) and disease incidence and mortality., Study Eligibility Criteria: For inclusion, a study had to report incidence or mortality for breast cancer according to baseline cadmium exposure category; be a prospective cohort, case-cohort or nested case-control study with a minimum one-year follow-up, and reporting effect estimates for all exposure categories., Study Appraisal and Synthesis Methods: Studies were evaluated using the ROBINS-E risk of bias tool. The effects in humans were assessed quantitatively using one-stage dose-response meta-analysis in a random effects meta-analytical model., Results: We identified 10 studies eligible for inclusion in the dose-response meta-analysis, six based on cadmium dietary intake, and four on urinary excretion levels. We found a marginal and imprecise positive relation between dietary cadmium intake and breast cancer, and no association when urinary cadmium excretion was used for exposure assessment. Compared to no exposure, at 20 µg/day of cadmium intake the summary risk ratio was 1.12 (95% confidence interval 0.80-1.56), while at 2 µg/g creatinine of cadmium excretion the summary risk ratio was 0.89 (95% confidence interval 0.38-2.14). Analysis restricted to post-menopausal women showed no association between either dietary or urinary cadmium and subsequent breast cancer incidence and mortality., Limitations and Conclusions: Overall, we found scant evidence of a positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer in selected subgroups cannot be entirely ruled out., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.

Background: Recent epidemiological findings investigate effects of exposure to air pollution on neurodegenerative disease. We performed a systematic review and meta-analysis to investigate the association between air pollution exposure and Parkinson's disease (PD)., Methods: We performed an extensive literature search in PubMed and Google Scholar databases and further searched for unpublished results in conference abstracts until November 2018. We identified 102 unique studies referring to air pollution and PD, from which 15 were included in the meta-analyses. We applied random-effects models to combine risk estimates and investigated between studies heterogeneity. We assessed publication bias through plots and the Egger's test in cases of sufficient number of studies. We assessed associations accounting for multi-pollutant exposures and effect modification patterns by sex and smoking habits., Results: We identified 13 reports investigating associations of PD with long-term exposure to regulated air pollutants whilst two reported associations for short-term exposure to PM 2.5 . The pooled relative risk (RR) for incidence of PD following an increase in long-term exposure for 10 μg/m 3 in PM 2.5 was 1.06 (95% Confidence Interval (CI): 0.99, 1.14) and in NO 2 1.01 (95%CI: 0.98, 1.03), while for 5 ppb increase in O 3 1.01 (95% CI: 1.00, 1.02) and for 1 mg/m 3 in CO 1.34 (95% CI: 0.85, 2.10); the pooled RR for a hospital admission due to PD after a 10 μg/m 3 increase in PM 2.5 short-term exposure was 1.03 (95% CI: 1.01, 1.05). There was high heterogeneity between study-specific results for most of the analyses, attributed to different populations under study. Effects were robust to multi-pollutant adjustment while there were indications of higher particles' effects among non smokers., Conclusions: We found weak evidence for an association between air pollution, mostly originating from traffic, and PD. Although meta-analysis increases power to detect small associations in rare outcomes, further research is needed to elaborate our suggestive associations. Such results are of public health significance since population aging in developed countries is expected to increase incidence of PD., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: We followed up, in 2013, the subjects who lived near the Athens International Airport and had participated in the cross-sectional multicountry HYENA study in 2004-2006., Objective: To evaluate the association of exposure to aircraft and road traffic noise with the incidence of hypertension and other cardiovascular outcomes., Methods: From the 780 individuals who participated in the cross-sectional study, 537 were still living in the same area and 420 accepted to participate in the follow-up. Aircraft and road traffic noise exposure was based on the estimations conducted in 2004-2006, linking geocoded residential addresses of the participants to noise levels. We applied multiple logistic regression and Cox proportional hazards models, adjusting for potential confounders., Results: The incidence of hypertension was significantly associated with higher aircraft noise exposure during the night. Specifically, the OR for hypertension per 10 dB increase in Lnight aircraft noise exposure was 2.63 (95% CI 1.21 to 5.71). Doctor-diagnosed cardiac arrhythmia was significantly associated with Lnight aircraft noise exposure, when prevalent and incident cases were considered with an OR of 2.09 (95% CI 1.07 to 4.08). Stroke risk was also increased with increasing noise exposure but the association was not significant. Twenty-four-hour road traffic noise associations with the outcomes considered were weaker and less consistent., Conclusions: In conclusion, our cohort study suggests that long-term exposure to aircraft noise, particularly during the night, is associated with incident hypertension and possibly, also, cardiovascular effects., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)