Methods matter: a comparative review of health risk assessments for ambient air pollution in Switzerland

Objectives: Air pollution health risk assessments (AP-HRAs) provide a method to quantify health effects for entire populations. In Switzerland, AP-HRAs are included in Swiss assessments for Transport Externalities (STEs), ordered by public authorities since the 1990s. This study aimed to describe the differences among national and international AP-HRAs for Switzerland. Methods: We compared input data, approaches and results across AP-HRAs over time. Results and input data for each AP-HRA were expressed as a ratio compared to the most recent STE (in most cases STE-2010). Results: Substantial variation across AP-HRAs was found. For all-cause adult mortality attributed to particulate matter (the most frequent outcome-pollutant pair), the ratio in HRAs oscillated from 0.40 to 2.09 (times the STE-2010 value). Regarding input data, the ratio ranged from 0.69 to 1.26 for population exposure, from 0 to 1.81 for counterfactual scenario, from 0.96 to 1.13 for concentration-response function and from 1.03 to 1.13 for baseline health data. Conclusion: This study demonstrates that methods matter for AP-HRAs. Transparent and possibly standardized reporting of key input data and assumptions should be promoted to facilitate comparison of AP-HRAs

Mortality attributable to ambient fine particulate matter and nitrogen dioxide in Switzerland in 2019: use of two-pollutant effect estimates

INTRODUCTION: Air pollution health risk assessments have traditionally used single-pollutant effect estimates for one proxy ambient air pollutant such as PM(2.5). Two-pollutant effect estimates, i.e. adjusted for another correlated pollutant, theoretically enable the aggregation of pollutant-specific health effects minimizing double-counting. Our study aimed at estimating the adult mortality in Switzerland in 2019 attributable to PM(2.5) from a single-pollutant effect estimate and to the sum of PM(2.5) and NO(2) from two-pollutant estimates; comparing the results with those from alternative global, European and Swiss effect estimates. METHODS: For the single-pollutant approach, we used a PM(2.5) summary estimate of European cohorts from the project ELAPSE, recommended by the European Respiratory Society and International Society for Environmental Epidemiology (ERS-ISEE). To derive the two-pollutant effect estimates, we applied ELAPSE-based conversion factors to ERS-ISEE PM(2.5) and NO(2) single-pollutant effect estimates. Additionally, we used World Health Organization 2021 Air Quality Guidelines as counterfactual scenario, exposure model data from 2019 and Swiss lifetables. RESULTS: The single-pollutant effect estimate for PM(2.5) (1.118 [1.060; 1.179] per 10 mug/m(3)) resulted in 2240 deaths (21,593 years of life lost). Using our derived two-pollutant effect estimates (1.023 [1.012; 1.035] per 10 mug/m(3) PM(2.5) adjusted for NO(2) and 1.040 [1.023; 1.058] per 10 mug/m(3) NO(2) adjusted for PM(2.5)), we found 1977 deaths (19,071 years of life lost) attributable to PM(2.5) and NO(2) together (23% from PM(2.5)). Deaths using alternative effect estimates ranged from 1042 to 5059. DISCUSSION: Estimated premature mortality attributable to PM(2.5) alone was higher than to both PM(2.5) and NO(2) combined. Furthermore, the proportion of deaths from PM(2.5) was lower than from NO(2) in the two-pollutant approach. These seemingly paradoxical results, also found in some alternative estimates, are due to statistical imprecisions of underlying correction methods. Therefore, using two-pollutant effect estimates can lead to interpretation challenges in terms of causality

A Navier-Stokes Solver for Compressible Turbulent Flows on Quadtree and Octree Based Cartesian Grids

Cartesian grids represent a special extent in unstructured grid literature. They employ chiefly created algorithms to produce automatic meshing while simulating flows around complex geometries without considering shape of the bodies. In this article, firstly, it is intended to produce regionally developed Cartesian meshes for two dimensional and three dimensional, disordered geometries to provide solutions hierarchically. Secondly, accurate results for turbulent flows are developed by finite volume solver (GeULER-NaTURe) with both geometric and solution adaptations. As a result, a “hands-off” flow solver based on Cartesian grids as the preprocessor is performed using object-oriented programming. Spalart-Allmaras turbulence model added Reynolds Averaged Navier Stokes equations are solved for the flows around airfoils and wings. The solutions are validated and verified by one two dimensional and one three dimensional turbulent flow common test cases in literature. Both case studies disclose the efficaciousness of the developed codes and qualify in convergence and accuracy

Sickle cell trait in association with HB H : a new patient from the Mediterranean region

Only five Hb S heterozygotes with an associated Hb H Disease i.e. the ASH condition or AS: --/-α have been defined in molecular detail. These had ancestries of Saudi-Arabian, Black or mixed Black and Chinese origin. We have studied a sixth patient who was from Turkey. The propositus was detected at birth with Hb Bart's at 27.6%. This declined to 1.6% at nine months, while the proportion of Hb S which was 5.1% at one month increased to 18.0% at one year.peer-reviewe

Long-term exposure to traffic-related air pollution and stroke: a systematic review and meta-analysis

Background Stroke remains the second cause of death worldwide. The mechanisms underlying the adverse association of exposure to traffic-related air pollution (TRAP) with overall cardiovascular disease may also apply to stroke. Our objective was to systematically evaluate the epidemiological evidence regarding the associations of long-term exposure to TRAP with stroke. Methods PubMed and LUDOK electronic databases were searched systematically for observational epidemiological studies from 1980 through 2019 on long-term exposure to TRAP and stroke with an update in January 2022. TRAP was defined according to a comprehensive protocol based on pollutant and exposure assessment methods or proximity metrics. Study selection, data extraction, risk of bias (RoB) and confidence assessments were conducted according to standardized protocols. We performed meta-analyses using random effects models; sensitivity analyses were assessed by geographic area, RoB, fatality, traffic specificity and new studies. Results Nineteen studies were included. The meta-analytic relative risks (and 95% confidence intervals) were: 1.03 (0.98-1.09) per 1 μg/m3 EC, 1.09 (0.96-1.23) per 10 μg/m3 PM10, 1.08 (0.89-1.32) per 5 μg/m3 PM2.5, 0.98 (0.92; 1.05) per 10 μg/m3 NO2 and 0.99 (0.94; 1.04) per 20 μg/m3 NOx with little to moderate heterogeneity based on 6, 5, 4, 7 and 8 studies, respectively. The confidence assessments regarding the quality of the body of evidence and separately regarding the presence of an association of TRAP with stroke considering all available evidence were rated low and moderate, respectively. Conclusion The available literature provides low to moderate evidence for an association of TRAP with stroke

Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease

The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell–cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell–related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease

Genetic risk factors for cerebrovascular disease in children with sickle cell disease: design of a case-control association study and genomewide screen

BACKGROUND: The phenotypic heterogeneity of sickle cell disease is likely the result of multiple genetic factors and their interaction with the sickle mutation. High transcranial doppler (TCD) velocities define a subgroup of children with sickle cell disease who are at increased risk for developing ischemic stroke. The genetic factors leading to the development of a high TCD velocity (i.e. cerebrovascular disease) and ultimately to stroke are not well characterized. METHODS: We have designed a case-control association study to elucidate the role of genetic polymorphisms as risk factors for cerebrovascular disease as measured by a high TCD velocity in children with sickle cell disease. The study will consist of two parts: a candidate gene study and a genomewide screen and will be performed in 230 cases and 400 controls. Cases will include 130 patients (TCD ≥ 200 cm/s) randomized in the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study as well as 100 other patients found to have high TCD in STOP II screening. Four hundred sickle cell disease patients with a normal TCD velocity (TCD < 170 cm/s) will be controls. The candidate gene study will involve the analysis of 28 genetic polymorphisms in 20 candidate genes. The polymorphisms include mutations in coagulation factor genes (Factor V, Prothrombin, Fibrinogen, Factor VII, Factor XIII, PAI-1), platelet activation/function (GpIIb/IIIa, GpIb IX-V, GpIa/IIa), vascular reactivity (ACE), endothelial cell function (MTHFR, thrombomodulin, VCAM-1, E-Selectin, L-Selectin, P-Selectin, ICAM-1), inflammation (TNFα), lipid metabolism (Apo A1, Apo E), and cell adhesion (VCAM-1, E-Selectin, L-Selectin, P-Selectin, ICAM-1). We will perform a genomewide screen of validated single nucleotide polymorphisms (SNPs) in pooled DNA samples from 230 cases and 400 controls to study the possible association of additional polymorphisms with the high-risk phenotype. High-throughput SNP genotyping will be performed through MALDI-TOF technology using Sequenom's MassARRAY™ system. DISCUSSION: It is expected that this study will yield important information on genetic risk factors for the cerebrovascular disease phenotype in sickle cell disease by clarifying the role of candidate genes in the development of high TCD. The genomewide screen for a large number of SNPs may uncover the association of novel polymorphisms with cerebrovascular disease and stroke in sickle cell disease

A Multilevel Mhealth intervention Boosts adherence to Hydroxyurea in individuals With Sickle Cell Disease

Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval. We enrolled 293 patients (51% male; median age 27.5 years, 86.8% HbSS/HbSβ0-thalassemia). The mean change in PDC among 235 evaluable subjects increased (39.7% to 56.0%; P \u3c 0.001) and sustained (39.7% to 51.4%, P \u3c 0.001). Mean HbF increased (10.95% to 12.78%; P = 0.03). Self-reported pain frequency reduced (3.54 to 3.35 events/year; P = 0.041). InCharge Health was used ≥1 day by 199 of 235 participants (84.7% implementation; median usage: 17% study days; IQR: 4.8-45.8%). For individuals with ≥1 baseline admission for pain, admissions per 24 weeks declined from baseline through 24 weeks (1.97 to 1.48 events/patient, P = 0.0045) and weeks 25-36 (1.25 events/patient, P = 0.0015). PDC increased with app use (P \u3c 0.001), with the greatest effect in those with private insurance (P = 0.0078), older subjects (P = 0.033), and those with lower pain interference (P = 0.0012). Of the 89 providers (49 hematologists, 36 advanced care providers, 4 unreported), only 11.2% used HU toolbox ≥1/month on average. This use did not affect change in PDC. Tailoring mHealth solutions to address barriers to hydroxyurea adherence can potentially improve adherence and provide clinical benefits. A definitive randomized study is warranted. This trial was registered at www.clinicaltrials.gov as #NCT04080167

Changes in Serum Adenosine Deaminase Activity during Normal Pregnancy

Adenosine deaminase (ADA), an enzyme essential for the differentiation of lymphoid cells, has been used for monitoring diseases with altered immunity. The purpose of this study was to investigate the changes in serum ADA activity throughout normal pregnancy. We measured the catalytic values of serum ADA from 202 normal pregnant women using a commercial kit. Subjects were divided into four groups according to the gestational age in weeks (Gwks) (Group I: 5-9 Gwks [n=58]; Group II: 15-20 Gwks [n= 63]; Group III: 24-30 Gwks [n=34]; Group IV: 30-39 Gwks [n=47]). The serum ADA levels for the Groups I, II, III, and IV were as follows: 20.1±6.9 IU/L, 20.0±7.6 IU/L, 37.9±19.9 IU/L, and 24.5±8.6 IU/L, respectively. The serum ADA activity of group III was significantly higher than the other groups (p<0.05). However, there was no significant correlation between the Gwks and the serum ADA activity. Furthermore, other parameters, such as maternal age (p=0.29), gestational age at delivery (p=0.07), delivery mode (p=0.39), and birth weight (p=0.59) had no correlation with ADA activity. Reference values of serum ADA in normal pregnancy may provide important database for making clinical decisions in pregnancies complicated by conditions where cellular immunity has been altered