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Background Few studies have explored the role of air pollution in neurodegenerative processes, especially various types of dementia. Our aim was to evaluate the association between long-term exposure to air pollution and first hospitalization for dementia subtypes in a large administrative cohort. Methods We selected 350,844 subjects (free of dementia) aged 65–100 years at inclusion (21/10/2001) and followed them until 31/12/2013. We selected all subjects hospitalized for the first time with primary or secondary diagnoses of various forms of dementia. We estimated the exposure at residence using land use regression models for nitrogen oxides (NOx, NO 2 ) and particulate matter (PM) and a chemical transport model for ozone (O 3 ). We used Cox models to estimate the association between exposure and first hospitalization for dementia and its subtypes: vascular dementia (Vd), Alzheimer’s disease (Ad) and senile dementia (Sd). Results We selected 21,548 first hospitalizations for dementia (7497 for Vd, 7669 for Ad and 7833 for Sd). Overall, we observed a negative association between exposure to NO 2 (10 μg/m 3 ) and dementia hospitalizations (HR = 0.97; 95% CI: 0.96–0.99) and a positive association between exposure to O 3 , NOx and dementia hospitalizations, (O 3 : HR = 1.06; 95% CI: 1.04–1.09 per 10 μg/m 3 ; NOx: HR = 1.01; 95% CI: 1.00–1.02 per 20 μg/m 3 ).H. Exposure to NOx, NO 2 , PM 2.5 , and PM 10 was positively associated with Vd and negatively associated with Ad. Hospitalization for Sd was positively associated with exposure to O 3 (HR = 1.20; 95% CI: 1.15–1.24 per 10 μg/m 3 ). Conclusions Our results showed a positive association between exposure to NOx and O 3 and hospitalization for dementia and a negative association between NO 2 exposure and hospitalization for dementia. In the analysis by subtype, exposure to each pollutants (except O 3 ) demonstrated a positive association with vascular dementia, while O 3 exposure was associated with senile dementia. The results regarding vascular dementia are a clear indication that the brain effects of air pollution are linked with vascular damage.

Some recently proposed frontline therapies for malignant pleural mesothelioma (MPM) are very costly, yet their impact on quality of life and overall survival of these patients remains arguable. Given the high social toll of this aggressive occupational cancer, it is paramount to establish the real clinical benefit of these treatments. To directly compare and analyze the statistical robustness of the 3 randomized clinical trials (RCTs) of frontline therapies recommended for MPM since 2003. This comparative effectiveness study assessed the following phase 3 RCTs: the Mesothelioma Cisplatin Pemetrexed Study (MPS) of cisplatin plus pemetrexed vs cisplatin; the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) of cisplatin plus pemetrexed plus bevacizumab vs cisplatin plus pemetrexed; and the CheckMate743 (CM743) study of nivolumab plus ipilimumab vs cisplatin plus pemetrexed. Data collection dates for the RCTs ranged from April 1999 to April 2018. Data for this study were analyzed from February to October 2021. Patient selection criteria, superiority of the intervention groups, survival-inferred fragility index, and censoring patterns in each RCT. A total of 1501 patients were included in the analysis (1170 men [77.9%]; range of median age for treatment groups, 60 [IQR, 19-84] to 69 [IQR, 65-75] years). A virtual comparison of overall survival in MAPS vs the CM743 study showed no statistically significant difference (hazard ratio [HR], 0.97 [95% CI, 0.79-1.20]; P = .79), and the survival-inferred fragility index in the intention-to-treat (ITT) populations was as low as 0.22% of the total sample size in MPS, -0.45% of the total sample size in MAPS, and 0.99% of the total sample size in the CM743 trial. Moreover, reverse restricted mean survival time (RMST) analysis of overall survival using RMST-difference (RMST-D) demonstrated differential censoring in the ITT population of the CM743 trial favoring the control group (0.56 [95% CI, 0.18-0.94]; P = .004) and in the nonepithelioid group (reverse RMST-D, 0.90 [95% CI, 0.001-1.79]; P = .048). This comparative effectiveness study found no survival benefit in the CM743 trial over MAPS, despite the inclusion of patients with worse prognosis in the latter trial. Moreover, the statistical conclusions of all the examined trials were shown to be extremely fragile, and the findings of differential censoring in the CM743 trial and in the ITT nonepithelial subset raised additional areas of concern. These findings suggest that selection criteria, fragility, and censoring patterns may affect the original conclusions drawn for the respective trials, casting a shadow on the real benefit. This model of analysis lays a rigorous groundwork extendable to trials of all cancer treatments before their registration.

In Italy, few multicentre population-based studies on pregnancy outcomes are available. Therefore, we established a network of population-based birth cohorts in the cities of Turin, Reggio Emilia, Modena, Bologna, and Rome (northern and central Italy), to study the role of socioeconomic factors and air pollution exposure on term low birthweight, preterm births and the prevalence of small for gestational age. In this article, we will report the full methodology of the study and the first descriptive results. We linked 2007–2013 delivery certificates with municipal registry data and hospital records, and selected singleton livebirths from women who lived in the cities for the entire pregnancy, resulting in 211,853 births (63% from Rome, 21% from Turin and the remaining 16% from the three cities in Emilia-Romagna Region). We have observed that the association between socioeconomic characteristics and air pollution exposure varies by city and pollutant, suggesting a possible effect modification of both the city and the socioeconomic position on the impact of air pollution on pregnancy outcomes. This is the largest Italian population-based birth cohort, not distorted by selection mechanisms, which has also the advantage of being sustainable over time and easily transferable to other areas. Results from the ongoing multivariable analyses will provide more insight on the relative impact of different strands of risk factors and on their interaction, as well as on the modifying effect of the contextual characteristics. Useful recommendations for strategies to prevent adverse pregnancy outcomes may eventually derive from this study.

Living in areas with higher levels of surrounding greenness and access to urban green areas have been associated with beneficial health outcomes. Some studies suggested a beneficial influence on mortality, but the evidence is still controversial. We used longitudinal data from a large cohort to estimate associations of two measures of residential greenness exposure with cause-specific mortality and stroke incidence. We studied a population-based cohort of 1,263,721 residents in Rome aged [Formula: see text], followed from 2001 to 2013. As greenness exposure, we utilized the leaf area index (LAI), which expresses the tree canopy as the leaf area per unit ground surface area, and the normalized difference vegetation index (NDVI) within 300- and [Formula: see text] buffers around home addresses. We estimated the association between the two measures of residential greenness and the outcomes using Cox models, after controlling for relevant individual covariates and contextual characteristics, and explored potential mediation by air pollution [fine particulate matter with aerodynamic diameter [Formula: see text] [Formula: see text] and [Formula: see text]] and road traffic noise. We observed 198,704 deaths from nonaccidental causes, 81,269 from cardiovascular diseases [CVDs; 29,654 from ischemic heart disease (IHD)], 18,090 from cerebrovascular diseases, and 29,033 incident cases of stroke. Residential greenness, expressed as interquartile range (IQR) increase in LAI within [Formula: see text], was inversely associated with stroke incidence {hazard ratio (HR) 0.977 [95% confidence interval (CI): 0.961, 0.994]} and mortality for nonaccidental [HR 0.988 (95% CI: 0.981, 0.994)], cardiovascular [HR 0.984 (95% CI: 0.974, 0.994)] and cerebrovascular diseases [HR 0.964 (95% CI: 0.943, 0.985)]. Similar results were obtained using NDVI with 300- or [Formula: see text] buffers. Living in greener areas was associated with better health outcomes in our study, which could be partly due to reduced exposure to environmental hazards. Further research is required to understand the underlying mechanisms. https://doi.org/10.1289/EHP2854.

Background Because of poor knowledge of risks and benefits, prophylactic explantation of high BIA-ALCL risk breast implant (BI) is not indicated. Several surgical risks have been associated with BI surgery, with mortality being the most frightening. Primary aim of this study is to assess mortality rate in patients undergoing breast implant surgery for aesthetic or reconstructive indication. Materials and Methods In this retrospective observational cohort study, Breast Implant Surgery Mortality rate (BISM) was calculated as the perioperative mortality rate among 99,690 patients who underwent BI surgery for oncologic and non-oncologic indications. Mean age at first implant placement (A1P), implant lifespan (IL), and women’s life expectancy (WLE) were obtained from a literature review and population database. Results BISM rate was 0, and mean A1P was 34 years for breast augmentation, and 50 years for breast reconstruction. Regardless of indication, overall mean A1P can be presumed to be 39 years, while mean BIL was estimated as 9 years and WLE as 85 years. Conclusion This study first showed that the BISM risk is 0. This information, and the knowledge that BI patients will undergo one or more revisional procedures if not explantation during their lifetime, may help surgeons in the decision-making process of a pre-emptive substitution or explant in patients at high risk of BIA-ALCL. Our recommendation is that patients with existing macrotextured implants do have a relative indication for explantation and total capsulectomy. The final decision should be shared between patient and surgeon following an evaluation of benefits, surgical risks and comorbidities. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Given the increasing population eligible for transcatheter aortic valve implantation (TAVI), resource utilization has become an important focus in this setting. We aimed to estimate the change in the financial burden of TAVI therapy over 2 different periods. A probabilistic Markov model was developed to estimate the cost consequences of increased center experience and the introduction of newer-generation TAVI devices compared with an earlier TAVI period in a cohort of 6,000 patients. The transition probabilities and hospitalization costs were retrieved from the OBSERVANT (Observational Study of Effectiveness of AVR-TAVI procedures for severe Aortic steNosis Treatment) and OBSERVANT II (Observational Study of Effectiveness of TAVI with new generation deVices for severe Aortic stenosis Treatment) studies, including 1,898 patients treated with old-generation devices and 1,417 patients treated with new-generation devices. The propensity score matching resulted in 853 pairs, with well-balanced baseline risk factors. The mean EuroSCORE II (6.6% vs 6.8%, p = 0.76) and the mean age (82.0 vs 82.1 y, p = 0.62) of the early TAVI period and new TAVI period were comparable. The new TAVI period was associated with a significant reduction in rehospitalizations (−30.5% reintervention, −25.2% rehospitalization for major events, and −30.8% rehospitalization for minor events) and a 20% reduction in 1-year mortality. These reductions resulted in significant cost savings over a 1-year period (−€4.1 million in terms of direct costs and −€19.7 million considering the additional cost of the devices). The main cost reduction was estimated for rehospitalization, accounting for 79% of the overall cost reduction (not considering the costs of the devices). In conclusion, the introduction of new-generation TAVI devices, along with increased center experience, led to significant cost savings at 1-year compared with an earlier TAVI period, mainly because of the reduction in rehospitalization costs.

Clinically relevant survival outcomes, including cure fraction estimates, and long-term survival outcomes of paediatric CNS tumours from large-scale databases have not been reported for Europe. Moreover, various biases hinder direct geographical comparisons, thereby limiting the effective translation of population-based findings into cancer care, surveillance, and research. We aimed to estimate these survival outcomes across Europe through the EUROCARE database. In this population-based study, we analysed survival data from the EUROCARE-6 database from children younger than 15 years with a CNS tumour across 31 European countries. For the period 2008–13, we estimated observed survival via the actuarial method, and 5-year observed survival was reported at the European level and national level for four major CNS tumour groups. For the period 1998–2013, cure fraction was estimated through a mixture cure model assuming constant long-term mortality from other causes. Additionally, model-based 10-year and 15-year survival were estimated. For observed survival analyses, 13 782 tumour cases were included. 5-year observed survival was 72% (95% CI 68 to 75) for ependymomas, 92% (91 to 93) for low-grade gliomas, 47% (45 to 49) for high-grade gliomas, 24% (21 to 27) for high-grade gliomas excluding glioma not otherwise specified, and 64% (62 to 67) for medulloblastomas. A total of 30 392 children were included in the cure fraction analysis. During the study period, the largest absolute increase in cure fraction was observed for ependymomas from 65% (57 to 73) in 1998–2001 to 79% (69 to 89) in 2010–13, whereas low-grade gliomas increased from from 89% (85 to 94) to 95% (89 to 100), high-grade gliomas had a 6 percentage point change increase (2 to 10), and medulloblastomas increased from 52% (49 to 55) to 56% (51 to 60). The estimated 10-year and 15-year survival rates were highest for low-grade gliomas at 90·6% (89·4 to 91·7) at 10 years and 88·5% (87·2 to 89·8) at 15 years, whereas the lowest survival rates were observed for high-grade gliomas excluding glioma not otherwise specified at 20·5% (17·0 to 24·1) and 19·0% (15·6 to 22·5). This study is the first to report a comprehensive evaluation of survival parameters for paediatric CNS tumour patients in Europe. These outcomes are important to evaluate advances in care for children with a CNS tumour. Princess Máxima Center for Pediatric Oncology and Associazione Italiana per la Ricerca sul Cancro.

Few studies have explored the role of air pollution in neurodegenerative processes, especially various types of dementia. Our aim was to evaluate the association between long-term exposure to air pollution and first hospitalization for dementia subtypes in a large administrative cohort. We selected 350,844 subjects (free of dementia) aged 65-100 years at inclusion (21/10/2001) and followed them until 31/12/2013. We selected all subjects hospitalized for the first time with primary or secondary diagnoses of various forms of dementia. We estimated the exposure at residence using land use regression models for nitrogen oxides (NOx, NO.sub.2) and particulate matter (PM) and a chemical transport model for ozone (O.sub.3). We used Cox models to estimate the association between exposure and first hospitalization for dementia and its subtypes: vascular dementia (Vd), Alzheimer's disease (Ad) and senile dementia (Sd). We selected 21,548 first hospitalizations for dementia (7497 for Vd, 7669 for Ad and 7833 for Sd). Overall, we observed a negative association between exposure to NO.sub.2 (10 [mu]g/m.sup.3) and dementia hospitalizations (HR = 0.97; 95% CI: 0.96-0.99) and a positive association between exposure to O.sub.3, NOx and dementia hospitalizations, (O.sub.3: HR = 1.06; 95% CI: 1.04-1.09 per 10 [mu]g/m.sup.3; NOx: HR = 1.01; 95% CI: 1.00-1.02 per 20 [mu]g/m.sup.3).H. Exposure to NOx, NO.sub.2, PM.sub.2.5, and PM.sub.10 was positively associated with Vd and negatively associated with Ad. Hospitalization for Sd was positively associated with exposure to O.sub.3 (HR = 1.20; 95% CI: 1.15-1.24 per 10 [mu]g/m.sup.3). Our results showed a positive association between exposure to NOx and O.sub.3 and hospitalization for dementia and a negative association between NO.sub.2 exposure and hospitalization for dementia. In the analysis by subtype, exposure to each pollutants (except O.sub.3) demonstrated a positive association with vascular dementia, while O.sub.3 exposure was associated with senile dementia. The results regarding vascular dementia are a clear indication that the brain effects of air pollution are linked with vascular damage.