Call for Action to Target Interhospital Variation in Cardiovascular Mortality, Readmissions, and Length-of-Stay: Results of a National Population Analysis.

BACKGROUND: Excessive interhospital variation threatens healthcare quality. Data on variation in patient outcomes across the whole cardiovascular spectrum are lacking. We aimed to examine interhospital variability for 28 cardiovascular All Patient Refined-Diagnosis-related Groups (APR-DRGs). METHODS: We studied 103,299 cardiovascular admissions in 99 (98%) Belgian acute-care hospitals between 2012 and 2018. Using generalized linear mixed models, we estimated hospital-specific and APR-DRG-specific risk-standardized rates for in-hospital mortality, 30-day readmissions, and length-of-stay above the APR-DRG-specific 90th percentile. Interhospital variation was assessed based on estimated variance components and time trends between the 2012-2014 and 2016-2018 periods were examined. RESULTS: There was strong evidence of interhospital variation, with statistically significant variation across the 3 outcomes for 5 APR-DRGs after accounting for patient and hospital factors: percutaneous cardiovascular procedures with acute myocardial infarction, heart failure, hypertension, angina pectoris, and arrhythmia. Medical diagnoses, with in particular hypertension, heart failure, angina pectoris, and cardiac arrest, showed strongest variability, with hypertension displaying the largest median odds ratio for mortality (2.51). Overall, hospitals performing at the upper-quartile level should achieve improvements to the median level, and an annual 633 deaths, 322 readmissions, and 1578 extended hospital stays could potentially be avoided. CONCLUSIONS: Analysis of interhospital variation highlights important outcome differences that are not explained by known patient or hospital characteristics. Targeting variation is therefore a promising strategy to improve cardiovascular care. Considering their treatment in multidisciplinary teams, policy makers, and managers should prioritize heart failure, hypertension, cardiac arrest, and angina pectoris improvements by targeting guideline implementation outside the cardiology department.

Exposure to a Mixture of Endocrine-Disrupting Chemicals and Metabolic Outcomes in Belgian Adolescents.

Childhood exposure to endocrine-disrupting chemicals (EDCs), either alone or in mixtures, may affect metabolic outcomes, yet existing evidence remains inconclusive. In our study of 372 adolescents from the Flemish Environment and Health Study (FLEHS IV, 2017-2018), we measured 40 known and suspected EDCs and assessed metabolic outcomes, including body mass index z-score (zBMI), abdominal obesity (AO), total cholesterol (TC), and triglycerides (TG). We applied Bayesian kernel machine regression (BKMR) and Bayesian penalized horseshoe regression for variable selection and then built multivariate generalized propensity score (mvGPS) models to provide an overview of the effects of selected EDCs on metabolic outcomes. As a result, BKMR and horseshoe together identified five EDCs associated with zBMI, three with AO, three with TC, and five with TG. Through mvGPS analysis, monoiso-butyl phthalate (MIBP), polychlorinated biphenyl (PCB-170), and hexachlorobenzene (HCB) each showed an inverse association with zBMI, as did PCB-170 with AO. Copper (Cu) was associated with higher TC and TG, except in boys where it was linked to lower TG. Additionally, monoethyl phthalate (MEP) and monobenzyl phthalate (MBzP) were associated with higher TG. To conclude, our findings support the association between certain chemicals (Cu, MEP, and MBzP) and elevated lipid levels, aligning with prior studies. Further investigation is needed for sex-specific effects.

Association of air pollution and green space with all-cause general practitioner and emergency room visits: A cross-sectional study of young people and adults living in Belgium.

BACKGROUND: Residing in areas with lower levels of air pollution and higher green space is beneficial to physical and mental health. We investigated associations of PM2.5, tree cover and grass cover with in-hours and out-of-hours GP visits and ER visits, for young people and adults. We estimated potential cost savings of GP visits attributable to high PM2.5. METHODS: We linked individual-level health insurance claims data of 315,123 young people (10-24 years) and 885,988 adults (25-64 years) with census tract-level PM2.5, tree cover and grass cover. Deploying negative binomial generalized linear mixed models, we estimated associations between quartile exposures and the three outcome measures. RESULTS: For in-hours and out-of-hours GP visits, among young people as well as adults, statistically significant pairwise differences between quartiles suggested increasing beneficial effects with lower PM2.5. The same outcomes were statistically significantly less frequent in quartiles with highest tree cover (>30.00%) compared to quartiles with lower tree cover, but otherwise pairwise differences were not statistically significant. These associations largely persisted in rural and urban areas. Among adults living in urban areas lower grass cover was associated with increased in-hours GP visits and ER visits. Assuming causality, reducing PM2.5 levels to the lowest quartile (4.91-7.49 µg/m³), among adults, 195,964 in-hours and 74,042 out-of-hours GP visits could be avoided annually. Among young people, 27,457 in-hours and 22,423 out-of-hours GP visits could be avoided annually. Nationally, this amounts to an annual potential cost saving of €43 million (€5.7 million in out-of-pocket payments and €37.2 million in compulsory health insurance). CONCLUSION: Higher ambient PM2.5 and lower tree cover show associations with higher non-urgent and urgent medical care utilization. These findings confirm the importance of reducing air pollution and fostering green zones, and that such policies may contribute positively to economic growth.

A Breakthrough Improvement Collaborative Significantly Reduces Hospital Stay After Elective Colectomy for Cancer Across a Healthcare System.

OBJECTIVE: This multicenter study aimed to assess (1) the effect of an improvement collaborative on enhanced recovery after surgery (ERAS) protocol adherence after elective colectomy and (2) the association between adherence and patient outcomes. BACKGROUND: ERAS pathways provide a framework to standardize care processes and improve postoperative outcomes in patients after colon surgery. Despite growing evidence of its effectiveness, adherence to these guidelines remains a challenge. METHODS: This prospective, multicenter collaborative was initiated throughout 11 hospitals in Flanders, Belgium. A structured audit tool was used to study patient outcomes and adherence to 12 ERAS components, defined by the collaborative. Three retrospective audits (based on patient record analysis) were conducted in 2017, 2019, and 2021, respectively. RESULTS: Overall, 740 patients were included (45.4% female; mean±SD age, 71±12 years). The overall adherence increased from 42.8% in 2017 to 58.4% in 2019 and 69.2% in 2021. Compared with low adherence, length of stay was increasingly reduced by 1.3 days for medium [95% confidence interval (95% CI): -2.5; 0.0], 3.6 days for high (95% CI: -4.9; -2.2), and up to 4.4 days for very high adherence (95% CI: -6.1; -2.7). Corresponding odds ratios for postoperative complications were 0.62 (95% CI: 0.33; 1.17), 0.19 (95% CI: 0.09; 0.43), and 0.14 (95% CI: 0.05; 0.39), respectively. No increase in 30-day readmissions was observed. CONCLUSIONS: A peer-constructed improvement collaborative effectively increases adherence to an ERAS protocol in individual hospitals. Across time, length of stay and postoperative complications decreased significantly, and a dose-response relationship was observed.

High temperatures trigger suicide mortality in Brussels, Belgium: A case-crossover study (2002-2011).

BACKGROUND: Temperature may trigger the risk of suicide, however, the extent and shape of the associations show geographical variation. Here, we investigate the short-term effects of temperature on suicide deaths occurring in Brussels between January 1st, 2002 and December 31st, 2011. METHODS: We conducted a bidirectional time-stratified case-crossover study with cases being suicide deaths occurring among Brussels residents aged 5 years or older. Cases were matched by day of the week with control days from the same month and year. The exposure was the daily average temperature measured at the Uccle station (Brussels) and obtained from the Belgian Royal Meteorological Institute. We combined conditional logistic regression with distributed lag non-linear models (DLNM) to obtain one week (lag 0-6) cumulative risk ratios (RR) and their 95% confidence intervals (CI) for the effects of moderate and extreme cold (5th and 1st percentiles of temperature, respectively) and moderate and extreme heat (95th and 99th percentiles of temperature, respectively), relative to the median temperature. RESULTS: In total, 1891 suicide deaths were included. The median temperature was 11.6 °C, moderate and extreme cold temperatures were 0 and -3.1 °C, respectively, and moderate and extreme high temperatures were 20.9 and 24.4 °C, respectively. The cumulative risk of suicide mortality was almost twice higher among lags 0 to 6 for both moderate and extreme heat, relative to the period median temperature (e.g. moderate heat RR = 1.80 CI:1.27-2.54). No statistically significant associations were observed for cold temperatures. CONCLUSIONS: In Brussels, a western European city with temperate climate, high temperatures may trigger suicide deaths up to one week later. In the context of climate change, adaptation strategies must take into consideration the effects of temperature on mental health.

Lower iodine storage in the placenta is associated with gestational diabetes mellitus.

BACKGROUND: The micronutrient iodine is essential for a healthy intrauterine environment and is required for optimal fetal growth and neurodevelopment. Evidence linking urinary iodine concentrations, which mainly reflects short-term iodine intake, to gestational diabetes mellitus (GDM) is inconclusive. Although the placental concentrations would better reflect the long-term gestational iodine status, no studies to date have investigated the association between the placental iodine load and the risk at GDM. Moreover, evidence is lacking whether placental iodine could play a role in biomarkers of insulin resistance and ß-cell activity. METHODS: We assessed the incidence of GDM between weeks 24 and 28 of gestation for 471 mother-neonate pairs from the ENVIRONAGE birth cohort. In placentas, we determined the iodine concentrations. In maternal and cord blood, we measured the insulin concentrations, the Homeostasis Model Assessment (HOMA) for insulin resistance (IR) index, and ß-cell activity. Logistic regression was used to estimate the odds ratios (OR) of GDM, and the population attributable factor (PAF) was calculated. Generalized linear models estimated the changes in insulin, HOMA-IR, and ß-cell activity for a 5 µg/kg increase in placental iodine. RESULTS: Higher placental iodine concentrations decreased the risk at GDM (OR = 0.82; 95%CI 0.72 to 0.93; p = 0.003). According to the PAF, 54.2% (95%CI 11.4 to 82.3%; p = 0.0006) of the GDM cases could be prevented if the mothers of the lowest tertile of placental iodine would have placental iodine levels as those belonging to the highest tertile. In cord blood, the plasma insulin concentration was inversely associated with the placental iodine load (ß = - 4.8%; 95%CI - 8.9 to - 0.6%; p = 0.026). CONCLUSIONS: Higher concentrations of placental iodine are linked with a lower incidence of GDM. Moreover, a lower placental iodine load is associated with an altered plasma insulin concentration, HOMA-IR index, and ß-cell activity. These findings postulate that a mild-to-moderate iodine deficiency could be linked with subclinical and early-onset alterations in the normal insulin homeostasis in healthy pregnant women. Nevertheless, the functional link between gestational iodine status and GDM warrants further research.

A decade of commitment to hospital quality of care: overview of and perceptions on multicomponent quality improvement policies involving accreditation, public reporting, inspection and pay-for-performance.

BACKGROUND: Quality improvement (QI) initiatives such as accreditation, public reporting, inspection and pay-for-performance are increasingly being implemented globally. In Flanders, Belgium, a government policy for acute-care hospitals incorporates aforementioned initiatives. Currently, questions are raised on the sustainability of the present policy. OBJECTIVE: First, to summarise the various initiatives hospitals have adopted under government encouragement between 2008 and 2019. Second, to study the perspectives of healthcare stakeholders on current government policy. METHODS: In this multi-method study, we collected data on QI initiative implementation from governmental and institutional sources and through an online survey among hospital quality managers. We compiled an overview of QI initiative implementation for all Flemish acute-care hospitals between 2008 (n = 62) and 2019 (n = 53 after hospital mergers). Stakeholder perspectives were assessed via a second survey available to all healthcare employees and a focus group with healthcare policy experts was consulted. Variation between professions was assessed. RESULTS: QI initiatives have been increasingly implemented, especially from 2016 onwards, with the majority (87%) of hospitals having obtained a first accreditation label and all hospitals publicly reporting performance indicators, receiving regular inspections and having entered the pay-for-performance initiative. On the topic of external international accreditation, overall attitudes within the survey were predominantly neutral (36.2%), while 34.5% expressed positive and 29.3% negative views towards accreditation. In examining specific professional groups in-depth, we learned 58% of doctors regarded accreditation negatively, while doctors were judged to be the largest contributors to quality according to the majority of respondents. CONCLUSIONS: Hospitals have demonstrated increased efforts into QI, especially since 2016, while perceptions on currently implemented QI initiatives among healthcare stakeholders are heterogeneous. To assure quality of care remains a top-priority for acute-care hospitals, we recommend a revision of the current multicomponent quality policy where the adoption of all initiatives is streamlined and co-created bottom-up.

Is a hospital quality policy based on a triad of accreditation, public reporting and inspection evidence-based? A narrative review.

BACKGROUND: Since 2009, hospital quality policy in Flanders, Belgium, is built around a quality-of-care triad, which encompasses accreditation, public reporting (PR) and inspection. Policy makers are currently reflecting on the added value of this triad. METHODS: We performed a narrative review of the literature published between 2009 and 2020 to examine the evidence base of the impact accreditation, PR and inspection, both individually and combined, has on patient processes and outcomes. The following patient outcomes were examined: mortality, length of stay, readmissions, patient satisfaction, adverse outcomes, failure to rescue, adherence to process measures and risk aversion. The impact of accreditation, PR and inspection on these outcomes was evaluated as either positive, neutral (i.e. no impact observed or mixed results reported) or negative. OBJECTIVES: To assess the current evidence base on the impact of accreditation, PR and inspection on patient processes and outcomes. RESULTS: We identified 69 studies, of which 40 were on accreditation, 24 on PR, three on inspection and two on accreditation and PR concomitantly. Identified studies reported primarily low-level evidence (level IV, n = 53) and were heterogeneous in terms of implemented programmes and patient populations (often narrow in PR research). Overall, a neutral categorization was determined in 30 articles for accreditation, 23 for PR and four for inspection. Ten of these recounted mixed results. For accreditation, a high number (n = 12) of positive research on adherence to process measures was discovered. CONCLUSION: The individual impact of accreditation, PR and inspection, the core of Flemish hospital quality, was found to be limited on patient outcomes. Future studies should investigate the combined effect of multiple quality improvement strategies.

COVID-19 is having a destructive impact on health-care workers' mental well-being.

BACKGROUND: The coronavirus disease 2019 (COVID-19) may aggravate workplace conditions that impact health-care workers' mental health. However, it can also place other stresses on workers outside of their work. This study determines the effect of COVID-19 on symptoms of negative and positive mental health and the workforce's experience with various sources of support. Effect modification by demographic variables was also studied. METHODS: A cross-sectional survey study, conducted between 2 April and 4 May 2020 (two waves), led to a convenience sample of 4509 health-care workers in Flanders (Belgium), including paramedics (40.6%), nurses (33.4%), doctors (13.4%) and management staff (12.2%). About three in four were employed in university and acute hospitals (29.6%), primary care practices (25.7%), residential care centers (21.3%) or care sites for disabled and mental health care. In each of the two waves, participants were asked how frequently (on a scale of 0-10) they experienced positive and negative mental health symptoms during normal circumstances and during last week, referred to as before and during COVID-19, respectively. These symptoms were stress, hypervigilance, fatigue, difficulty sleeping, unable to relax, fear, irregular lifestyle, flashback, difficulty concentrating, feeling unhappy and dejected, failing to recognize their own emotional response, doubting knowledge and skills and feeling uncomfortable within the team. Associations between COVID-19 and mental health symptoms were estimated by cumulative logit models and reported as odds ratios. The needed support was our secondary outcome and was reported as the degree to which health-care workers relied on sources of support and how they experienced them. RESULTS: All symptoms were significantly more pronounced during versus before COVID-19. For hypervigilance, there was a 12-fold odds (odds ratio 12.24, 95% confidence interval 11.11-13.49) during versus before COVID-19. Positive professional symptoms such as the feeling that one can make a difference were less frequently experienced. The association between COVID-19 and mental health was generally strongest for the age group 30-49 years, females, nurses and residential care centers. Health-care workers reported to rely on support from relatives and peers. A considerable proportion, respectively, 18 and 27%, reported the need for professional guidance from psychologists and more support from their leadership. CONCLUSIONS: The toll of the crisis has been heavy on health-care workers. Those who carry leadership positions at an organizational or system level should take this opportunity to develop targeted strategies to mitigate key stressors of health-care workers' mental well-being.

An 18 year data-linkage study on the association between air pollution and acute limb ischaemia.

Background: There is limited information regarding the effects of air pollutants, such as nitrogen oxides (NOx), nitric oxide (NO2), nitrous oxide (NO) and particulate matter with a diameter smaller than 10 µm (PM10), on acute limb ischaemia (ALI), a peripheral arterial disease (PAD) often with a poor clinical outcome. Patients and methods: We conducted an 18-year retrospective cohort study using routinely collected healthcare records from Ninewells Hospital, Dundee, and Perth Royal Infirmary, in Tayside, Scotland, UK from 2000 to 2017. ALI hospitalisation events and deaths were linked to daily NOx, NO2, NO and PM10 levels extracted from publicly available data over this same time period. Distributed lag models were used to estimate risk ratios for ALI hospitalisation and for ALI mortality, adjusting for temperature, humidity, day of the week, month and public holiday. Results: 5,608 hospital admissions in 2,697 patients were identified over the study period (mean age 71.2 years, ±11.1). NOx and NO were associated with an increase of ALI hospital admissions on days of exposure to pollutant (p=.018), while PM10 was associated with a cumulative (lag 0-9 days) increase (p=.027) of ALI hospital admissions in our study. There was no increase of ALI mortality associated with pollution levels. Conclusions: ALI hospital admissions were positively associated with ambient NOx and NO on day of high measured pollution levels and a cumulative effect was seen with PM10.

Determinants of placental iodine concentrations in a mild-to-moderate iodine-deficient population: an ENVIRONAGE cohort study.

BACKGROUND: Iodine is an essential trace element for the production of thyroid hormones, and plays a key role during the gestational period for optimal foetal growth and (neuro-)development. To this day, iodine deficiency remains a global burden. Previous studies indicate that the placenta can store iodine in a concentration-dependent manner and serve as a long-term storage supply, but studies on the determinants of long-term placental iodine load are limited. METHODS: The placental iodine concentrations were determined for 462 mother-neonate pairs from the ENVIRONAGE birth cohort (Limburg, Belgium). Sociodemographic and clinical variables were obtained from questionnaires and medical files. Determinants of placental iodine concentration were identified using stepwise multiple regression procedures (p value < 0.15). The biological significance of our findings was investigated by measuring the plasma thyroid hormones in maternal and cord blood of 378 participants. RESULTS: A higher pre-pregnancy BMI, higher gestational weight gain, and alcohol consumption during pregnancy were linked with lower placental iodine storage. Multi-vitamin supplementation during pregnancy and longer gestation were associated with higher levels of placental iodine. Children born during the winter period had on average higher placental iodine levels. Besides, we found a significant positive time trend for placental iodine load over the study period 2013 to 2017. Lastly, we observed positive associations of both the maternal and cord plasma thyroxine concentrations with placental iodine load, emphasizing their biological link. CONCLUSIONS: This study identified some determinants likely presenting a risk of reduced iodine storage during the gestational period of life. Future studies should elucidate the effects of lower placental iodine load on neonatal health, and health later in life.

DNA methylation of insulin-like growth factor 2 and H19 cluster in cord blood and prenatal air pollution exposure to fine particulate matter.

BACKGROUND: The IGF2 (insulin-like growth factor 2) and H19 gene cluster plays an important role during pregnancy as it promotes both foetal and placental growth. We investigated the association between cord blood DNA methylation status of the IGF2/H19 gene cluster and maternal fine particulate matter exposure during fetal life. To the best of our knowledge, this is the first study investigating the association between prenatal PM2.5 exposure and newborn DNA methylation of the IGF2/H19. METHODS: Cord blood DNA methylation status of IGF2/H19 cluster was measured in 189 mother-newborn pairs from the ENVIRONAGE birth cohort (Flanders, Belgium). We assessed the sex-specific association between residential PM2.5 exposure during pregnancy and the methylation level of CpG loci mapping to the IGF2/H19 cluster, and identified prenatal vulnerability by investigating susceptible time windows of exposure. We also addressed the biological functionality of DNA methylation level in the gene cluster. RESULTS: Prenatal PM2.5 exposure was found to have genetic region-specific significant association with IGF2 and H19 during specific gestational weeks. The association was found to be sex-specific in both gene regions. Functionality of the DNA methylation was annotated by the association to fetal growth and cellular pathways. CONCLUSIONS: The results of our study provided evidence that prenatal PM2.5 exposure is associated with DNA methylation in newborns' IGF2/H19. The consequences within the context of fetal development of future phenotyping should be addressed.

The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation: a case-crossover analysis.

In bronchiectasis, exacerbations are believed to be triggered by infectious agents, but often no pathogen can be identified. We hypothesised that acute air pollution exposure may be associated with bronchiectasis exacerbations.We combined a case-crossover design with distributed lag models in an observational record linkage study. Patients were recruited from a specialist bronchiectasis clinic at Ninewells Hospital, Dundee, UK.We recruited 432 patients with clinically confirmed bronchiectasis, as diagnosed by high-resolution computed tomography. After excluding days with missing air pollution data, the final model for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) was based on 6741 exacerbations from 430 patients and for nitrogen dioxide (NO2) it included 6248 exacerbations from 426 patients. For each 10 µg·m-³ increase in PM10 and NO2, the risk of having an exacerbation that same day increased significantly by 4.5% (95% CI 0.9-8.3) and 3.2% (95% CI 0.7-5.8) respectively. The overall (lag zero to four) increase in risk of exacerbation for a 10 µg·m-3 increase in air pollutant concentration was 11.2% (95% CI 6.0-16.8) for PM10 and 4.7% (95% CI 0.1-9.5) for NO2 Subanalysis showed higher relative risks during spring (PM10 1.198 (95% CI 1.102-1.303), NO2 1.146 (95% CI 1.035-1.268)) and summer (PM10 2.142 (95% CI 1.785-2.570), NO2 1.352 (95% CI 1.140-1.602)) when outdoor air pollution exposure would be expected to be highest.In conclusion, acute air pollution fluctuations are associated with increased exacerbation risk in bronchiectasis.

Sex-specific associations between telomere length and candidate miRNA expression in placenta.

BACKGROUND: In the early-life environment, proper development of the placenta is essential for both fetal and maternal health. Telomere length at birth has been related to life expectancy. MicroRNAs (miRNAs) as potential epigenetic determinants of telomere length at birth have not been identified. In this study, we investigate whether placental miRNA expression is associated with placental telomere length at birth. METHODS: We measured the expression of seven candidate miRNAs (miR-16-5p, -20a-5p, -21-5p, -34a-5p, 146a-5p, -210-3p and -222-3p) in placental tissue at birth in 203 mother-newborn (51.7% girls) pairs from the ENVIRONAGE birth cohort. We selected miRNAs known to be involved in crucial cellular processes such as inflammation, oxidative stress, cellular senescence related to aging. Placental miRNA expression and relative average placental telomere length were measured using RT-qPCR. RESULTS: Both before and after adjustment for potential covariates including newborn's ethnicity, gestational age, paternal age, maternal smoking status, maternal educational status, parity, date of delivery and outdoor temperature during the 3rd trimester of pregnancy, placental miR-34a, miR-146a, miR-210 and miR-222 expression were significantly (p ≤ 0.03) and positively associated with placental relative telomere length in newborn girls. In newborn boys, only higher expression of placental miR-21 was weakly (p = 0.08) associated with shorter placental telomere length. Significant miRNAs explain around 6-8% of the telomere length variance at birth. CONCLUSIONS: Placental miR-21, miR-34a, miR-146a, miR-210 and miR-222 exhibit sex-specific associations with telomere length in placenta. Our results indicate miRNA expression in placental tissue could be an important determinant in the process of aging starting from early life onwards.

Relationships between aeroallergen levels and hospital admissions for asthma in the Brussels-Capital Region: a daily time series analysis.

BACKGROUND: Outdoor pollen grain and fungal spore concentrations have been associated with severe asthma exacerbations at the population level. The specific impact of each taxon and the concomitant effect of air pollution on these symptoms have, however, still to be better characterized. This study aimed to investigate the short-term associations between ambient concentrations of various aeroallergens and hospitalizations related to asthma in the Brussels-Capital Region (Belgium), an area recording especially high rates of admissions. METHODS: Based on administrative records of asthma hospitalizations and regular monitoring of 11 tree/herbaceous pollen taxa and 2 fungal spore taxa, daily time series analyses covering the 2008-2013 period were performed. Effects up to 6 days after exposure were captured by combining quasi-Poisson regression with distributed lag models, adjusting for seasonal and long-term trends, day of the week, public holidays, mean temperature and relative humidity. Effect modification by age and air pollution (PM, NO2, O3) was tested. RESULTS: A significant increase in asthma hospitalizations was observed for an interquartile range increase in grass (5.9%, 95% CI: 0.0, 12.0), birch (3.2%, 95% CI: 1.1, 5.3) and hornbeam (0.7%, 95% CI: 0.2, 1.3) pollen concentrations. For several taxa including grasses, an age modification effect was notable, the hospitalization risk tending to be higher in individuals younger than 60 years. Air pollutants impacted the relationships too: the risk appeared to be stronger for grass and birch pollen concentrations in case of high PM10 and O3 concentrations respectively. CONCLUSIONS: These findings suggest that airborne grass, birch and hornbeam pollen are associated with severe asthma exacerbations in the Brussels region. These compounds appear to act in synergy with air pollution and to more specifically affect young and intermediate age groups. Most of these life-threatening events could theoretically be prevented with improved disease diagnosis/management and targeted communication actions.

Does air pollution trigger suicide? A case-crossover analysis of suicide deaths over the life span.

In addition to underlying health disorders and socio-economic or community factors, air pollution may trigger suicide mortality. This study evaluates the association between short-term variation in air pollution and 10 years of suicide mortality in Belgium. In a bidirectional time-stratified case-crossover design, 20,533 suicide deaths registered between January 1st 2002 and December 31st 2011 were matched by temperature with control days from the same month and year. We used municipality-level air pollution [particulate matter (PM10) and O3 concentrations] data and meteorology data. We applied conditional logistic regression models adjusted for duration of sunshine and day of the week to obtain odds ratios (OR) and their 95% CI for an increase of 10 µg/m3 in pollutant concentrations over different lag periods (lag 0, 0-1, 0-2, 0-3, 0-4, 0-5, and 0-6 days). Effect modification by season and age was investigated by including interaction terms. We observed significant associations of PM10 and O3 with suicide during summer (OR ranging from 1.02 to 1.07, p-values <0.05). For O3, significant associations were also observed during spring and autumn. Age significantly modified the associations with PM10, with statistically significant associations observed only among 5-14 year old children (lag 0-6: OR = 1.45; 95% CI: 1.03-2.04) and ≥85 years old (e.g. lag 0-4: OR = 1.17; 95% CI: 1.06-1.29). Recent increases in outdoor air pollutants such as PM10 or O3 can trigger suicide, particularly during warm periods, even at concentrations below the European thresholds. Furthermore, PM10 may have strong trigger effects among children and elderly population.

Short-term air pollution exposure decreases lung function: a repeated measures study in healthy adults.

BACKGROUND: Daily changes in ambient concentrations of particulate matter, nitrogen oxides and ozone are associated with increased cardiopulmonary morbidity and mortality, with the lungs and their function being a vulnerable target. METHODS: To evaluate the association between daily changes in air pollution and lung function in healthy adults we obtained annual lung function measurements from a routine worker health surveillance program not designed for research purposes. Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), FEV1/FVC and Peak Expiratory flow (PEF) from a cohort of 2449 employees were associated with daily measurements of PM10, NO2 and ozone at a nearby monitoring station in the North of Belgium. Repeated measures were available for the period 2011-2015. RESULTS: The mean (SD) PM10 concentration on the day of the lung function test was 24.9 (15.5) µg/m3. A 10 µg PM10/m3 increase on the day of the clinical examination was associated with a 18.9 ml lower FVC (95% CI: -27.5 to -10.3, p < 0.0001), 12.8 ml lower FEV1 (-19.1 to -6.5; p < 0.0001), and a 51.4 ml/s lower PEF (-75.0 to -27.0; p < 0.0001). The FEV1/FVC-ratio showed no associations. An increase of 10 µgNO2/m3 was associated with a reduction in PEF (-66.1 ml/s (-106.6 to -25.6; p < 0.001)) on the day of the examination. CONCLUSIONS: We found negative associations between daily variations in ambient air pollution and FVC, FEV1 and PEF in healthy adults.

Ambient Air Pollution-related Mortality in Dairy Cattle: Does It Corroborate Human Findings?

BACKGROUND: Despite insights for humans, short-term associations of air pollution with mortality to our knowledge have never been studied in animals. We investigated the association between ambient air pollution and risk of mortality in dairy cows and assessed effect modification by season. METHODS: We collected ozone (O3), particulate matter (PM10), and nitrogen dioxide (NO2) concentrations at the municipality level for 87,108 dairy cow deaths in Belgium from 2006 to 2009. We combined a case-crossover design with time-varying distributed lag models. RESULTS: We found acute and delayed associations between air pollution and dairy cattle mortality during the warm season. The increase in mortality for a 10 µg/m increase in 2-day (lag 0-1) O3 was 1.2% (95% confidence interval [CI] = 0.3%, 2.1%), and the corresponding estimates for a 10 µg/m increase in same-day (lag 0) PM10 and NO2 were 1.6% (95% CI = 0.0%, 3.1%) and 9.2% (95% CI = 6.3%, 12%), respectively. Compared with the acute increases, the cumulative 26-day (lag 0-25) estimates were considerably larger for O3 (3.0%; 95% CI = 0.2%, 6.0%) and PM10 (3.2%; 95% CI = -0.6%, 7.2%), but not for NO2 (1.4%; 95% CI = -4.9%, 8.2%). In the cold season, we only observed increased mortality risks associated with same-day (lag 0) exposure to NO2 (1.4%; 95% CI = -0.1%, 3.1%) and with 26-day (lag 0-25) exposure to O3 (4.6%; 95% CI = 2.2%, 7.0%). CONCLUSIONS: Our study adds to the epidemiologic findings in humans and reinforces the evidence on the plausibility of causal effects. Furthermore, our results indicate that air pollution associations go beyond short-term mortality displacement. (See video abstract at http://links.lww.com/EDE/B105.).

miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure.

INTRODUCTION: Air pollution, a risk factor for cardiovascular diseases, can exert its effects through the microcirculation. Retinal blood vessel width is considered a marker for microvascular health and is associated with short-term PM10 exposure. microRNAs are key regulators of complex biological processes in cardiovascular health and disease and miRNA expression can be affected by air pollution exposure. Studies investigating the effect of ambient air pollution exposure on miRNA expression in combination with an assessment of the microvasculature do not exist. METHODS: 50 healthy adults (50% women, 23-58 years old) were examined once a month from December 2014 until April 2015 in Flanders (Belgium). Fundus photos and venous blood samples were collected during the study visits. PM10 data were obtained from a nearby monitoring station. Image analysis was used to calculate the width of retinal blood vessels, represented as the Central Retinal Arteriolar/Venular Equivalent (CRAE/CRVE). Total miRNA was isolated from blood and the expression of miR-21, -146a and, -222 were measured using quantitative real-time PCR. Mixed models were used for statistical analysis. RESULTS: Each short-term increase of 10µg/m(3) PM10 during the 24h preceding the study visit was associated with a 0.58µm decrease (95% CI: -1.16, -0.0005; p=0.056) in CRAE, a 0.99µm increase (95% CI: 0.18, 1.80; p=0.021) in CRVE, a 6.6% decrease (95% CI: -11.07, -2.17; p=0.0038) in miR-21 expression and a 6.7% decrease (95% CI: -10.70, -2.75; p=0.0012) in miR-222 expression. Each 10% increase in miR-21 was associated with a 0.14µm increase (95% CI: 0.0060, 0.24; p=0.046) in CRAE whereas a similar increase in miR-222 expression was associated with a 0.28µm decrease (95% CI: -0.50, -0.062; p=0.016) in CRVE. These associations were also found in exposure windows ranging from 2h to 1 week. Finally, we observed that the association between PM10 exposure and CRAE was mediated by miRNA-21 expression. CONCLUSION: PM10 exposure was associated with retinal arteriolar narrowing and venular widening. PM10 exposure affected miRNAs that are involved in inflammatory and oxidative stress pathways. We suggest that miRNA changes may be relevant to explain the association between PM10 and retinal vessel calibers.

Mortality related to cold and heat. What do we learn from dairy cattle?

Extreme temperatures are associated with increased mortality among humans. Because similar epidemiologic studies in animals may add to the existing evidence, we investigated the association between ambient temperature and the risk of mortality among dairy cattle. We used data on 87,108 dairy cow deaths in Belgium from 2006 to 2009, and we combined a case-crossover design with distributed lag non-linear models. Province-specific results were combined in a multivariate meta-analysis. Relative to the estimated minimum mortality temperature of 15.4°C (75th percentile), the pooled cumulative relative risks over lag 0-25 days were 1.26 (95% CI: 1.11, 1.42) for extreme cold (1st percentile, -3.5°C), 1.35 (95% CI: 1.19, 1.54) for moderate cold (5th percentile, -0.3°C), 1.09 (95% CI: 1.02, 1.17) for moderate heat (95th percentile, 19.7°C), and 1.26 (95% CI: 1.08; 1.48) for extreme heat (99th percentile, 22.6°C). The temporal pattern of the temperature-mortality association was similar to that observed in humans, i.e. acute effects of heat and delayed and prolonged effects of cold. Seasonal analyses suggested that most of the temperature-related mortality, including cold effects, occurred in the warm season. Our study reinforces the evidence on the plausibility of causal effects in humans.