Financial Burden of Transcatheter Aortic Valve Implantation.

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.

Mortality Rate in Breast Implant Surgery: Is an Additional Procedure Worthwhile to Mitigate BIA-ALCL Risk?

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 .

Comparison of 3 Randomized Clinical Trials of Frontline Therapies for Malignant Pleural Mesothelioma.

Importance: 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. Objective: To directly compare and analyze the statistical robustness of the 3 randomized clinical trials (RCTs) of frontline therapies recommended for MPM since 2003. Design, Setting, and Participants: 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. Main Outcomes and Measures: Patient selection criteria, superiority of the intervention groups, survival-inferred fragility index, and censoring patterns in each RCT. Results: 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). Conclusions and Relevance: 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.

One-Year Outcomes and Trends over Two Eras of Transcatheter Aortic Valve Implantation in Real-World Practice.

BACKGROUND: Data reflecting the benefit of procedural improvements in real-world transcatheter aortic valve implantation (TAVI) practice are sparse. AIMS: To compare outcomes and trends of two TAVI eras from real Italian practice. METHODS: A total of 1811 and 2939 TAVI patients enrolled in the national, prospective OBSERVANT and OBSERVANT II studies in 2010-2012 and 2016-2018, respectively, were compared in a cohort study. Outcomes were adjusted using inverse propensity of treatment weighting and propensity score matching. RESULTS: The median age (83.0 (79.0-86.0) vs. 83.0 (79.0-86.0)) and EuroSCORE II (5.2 (3.2-7.7) vs. 5.1 (3.1-8.1)) of OBSERVANT and OBSERVANT II patients were similar. At 1 year, patients of the OBSERVANT II study had a significantly lower risk of all-cause death (10.6% vs. 16.3%, Hazard Ratio (HR) 0.63 (95% Confidence Interval (CI) 0.52-0.76)) and rehospitalization for heart failure (HF) (14.3% vs. 19.5%, Sub-distribution HR 0.71 (95%CI 0.60-0.84)), whereas rates of stroke (3.1% vs. 3.6%) and permanent pacemaker implantation (PPI) (16.6% vs. 18.0%) were comparable between study groups. CONCLUSIONS: Age and risk profile among patients undergoing TAVI in Italy remained substantially unchanged between the 2010-2012 and 2016-2018 time periods. After adjustment, patients undergoing TAVI in the most recent era had lower risk of all-cause death and rehospitalization for HF at 1 year, whereas rates of stroke and PPI did not differ significantly.

[Relationship between hospital volumes and health outcomes: epidemiological evidence supporting the revision process of the Ministry of Health Decree no. 70 of 2 April 2015.] / Relazione tra volumi di attività ed esiti dell'assistenza ospedaliera: evidenze epidemiologiche a supporto del processo di revisione del Decreto del Ministero della Salute n. 70 del 2 aprile 2015.

Since its enactment on 2 April 2015, the Decree of the Ministry of Health no.70 has provided a key framework for the reorganization of services to enhance the quality and safety of care. This decree presents the volume thresholds for a series of nosological areas and diagnostic-therapeutic procedures, aiming to improve healthcare outcomes. These thresholds are expected to be periodically updated based on the most recent scientific developments. AIM: In this perspective, this work intends to establish whether statistical correlations exist between volumes of activity and outcomes of hospital care. The scope is limited to several clinical conditions and therapeutic procedures for which specific indicators are provided by the National Healthcare Outcomes Programme (Programma Nazionale Esiti - PNE). METHODS: For each condition or procedure, the analysis shows the volume-outcome relationship by hospital centre by means of the Levenberg-Marquardt algorithm (software: XLSTAT). The existence of breakpoints is assessed through the use of segmented models (software: "segmented" R-Package). RESULTS: The results show a statistical correlation for the following: acute myocardial infarction (breakpoint: 91 hospitalizations per year; 95% CI: 81-101; p<0.0001); repair of an unruptured abdominal aortic aneurysm (breakpoint: 69 procedures per year; 95% CI: 52-86; p=0.146); lung cancer (breakpoint: 96 procedures per year; 95% CI: 60-132; p<0.01); knee arthroplasty (breakpoint: 91 procedures per year; 95% CI: 51-131; p=0.484). Conversely, the statistical analysis did not allow to accurately highlight a breakpoint for the isolated aorto-coronary bypass, percutaneous transluminal coronary angioplasty and hip arthroplasty. CONCLUSIONS: These results represent a useful knowledge contribution to support the revision process of the above-mentioned Decree. As regards the procedures that may not be currently assessed through this statistical analysis method, literature data is referred to that confirm that the current regulatory thresholds are in the safe range.

Impact of age, gender and heart failure on mortality trends after acute myocardial infarction in Italy.

BACKGROUND: The outcome of patients with acute myocardial infarction (AMI) may vary substantially based on baseline risk. We aimed at analyzing the impact of gender, age and heart failure (HF) on mortality trends, based on a nationwide, comprehensive and universal administrative database of AMI. METHODS: This is a nationwide cohort study of patients admitted with AMI from 2009 to 2018 in all Italian hospitals. In-hospital mortality rate (I-MR) and 1-year post-discharge mortality rate (1-Y-MR) were assessed. RESULTS: Among the 1,000,965 AMI events included in the analysis, 43.6% occurred in patients aged ≥75 years, 34.7% in females and 21.8% in AMI complicated by HF at the index hospitalization. Both I-MR and 1-Y-MR significantly decreased over time (from 8.87% to 6.72%; mean annual change -0.23%; confidence intervals (CI): - 0.26% to -0.20% and from 12.24% to 10.59%; mean annual change -0.18%; CI: - 0.24% to -0.13%, respectively). This trend was confirmed in younger and elderly AMI patients, in both sexes. In AMI patients complicated by HF, both I-MR and 1-Y-MR were markedly high, regardless of age and gender. CONCLUSIONS: This contemporary, nationwide study suggests that I-MR and 1-Y-MR are still elevated, albeit decreasing over time. Elderly patients and those with HF at the time of index admission, present a particularly high risk of fatal events, regardless of gender.

Long-term outcomes of self-expanding versus balloon-expandable transcatheter aortic valves: Insights from the OBSERVANT study.

OBJECTIVES: To compare clinical outcomes of balloon-expandable (BE) and self-expanding (SE) transcatheter aortic valves (TAVs) up to 5 years. BACKGROUND: To date, no robust, comparative data of BE and SE TAVs at long-term are available. METHODS: We considered a total of 1,440 patients enrolled in the multicenter OBSERVANT study and undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) with either supra-annular SE (n = 830, 57.6%) and intra-annular BE (n = 610, 42.4%) valves. Clinical outcomes of the two groups were compared after adjustment using inverse probability of treatment weighting (IPTW) and confirmed by sensitivity analysis with propensity score matching. RESULTS: Patients receiving SE valve showed a higher all-cause mortality at 5 years (Kaplan-Meier estimates 52.3% vs. 47.7%; Hazard ratio [HR] 1.18, 95% confidence interval [CI] 1.01-1.38, p = .04). Landmark analyses showed that there was a not statistically significant reversal of risk excess against the BE group starting from 3 years after TAVI (3-5 years HR 0.97, 95% CI 0.76-1.25, p = .86). Post-procedural, moderate/severe paravalvular regurgitation (PVR)(HR 1.46, 95% CI 1.14-1.87; p < .01) and acute kidney injury (AKI)(HR 3.89, 95% CI 2.47-6.38; p < .01) showed to be independent predictors of 5-year all-cause mortality in multivariable analysis. CONCLUSIONS: Considering the intrinsic limitations of the OBSERVANT study, we found that patients undergoing TF-TAVI with a supra-annular SE valve had a higher all-cause mortality compared to those receiving an intra-annular BE valve at 5 years. A late catch up phenomenon of patients receiving the BE valve was observed beyond 3 years. Post-procedural moderate/severe PVR seems to play a crucial role in determining this finding. Comparative studies of new generation devices with longer follow-up are needed to evaluate the benefit of each specific TAV type.

A novel, comprehensive tool for predicting 30-day mortality after surgical aortic valve replacement.

OBJECTIVES: We sought to develop and validate a novel risk assessment tool for the prediction of 30-day mortality after surgical aortic valve replacement incorporating a patient's frailty. METHODS: Overall, 4718 patients from the multicentre study OBSERVANT was divided into derivation (n = 3539) and validation (n = 1179) cohorts. A stepwise logistic regression procedure and a criterion based on Akaike information criteria index were used to select variables associated with 30-day mortality. The performance of the regression model was compared with that of European System for Cardiac Operative Risk Evaluation (EuroSCORE) II. RESULTS: At 30 days, 90 (2.54%) and 35 (2.97%) patients died in the development and validation data sets, respectively. Age, chronic obstructive pulmonary disease, concomitant coronary revascularization, frailty stratified according to the Geriatric Status Scale, urgent procedure and estimated glomerular filtration rate were independent predictors of 30-day mortality. The estimated OBS AVR score showed higher discrimination (area under curve 0.76 vs 0.70, P < 0.001) and calibration (Hosmer-Lemeshow P = 0.847 vs P = 0.130) than the EuroSCORE II. The higher performances of the OBS AVR score were confirmed by the decision curve, net reclassification index (0.46, P = 0.011) and integrated discrimination improvement (0.02, P < 0.001) analyses. Five-year mortality increased significantly along increasing deciles of the OBS AVR score (P < 0.001). CONCLUSIONS: The OBS AVR risk score showed high discrimination and calibration abilities in predicting 30-day mortality after surgical aortic valve replacement. The addition of a simplified frailty assessment into the model seems to contribute to an improved predictive ability over the EuroSCORE II. The OBS AVR risk score showed a significant association with long-term mortality.

An Italian Network of Population-Based Birth Cohorts to Evaluate Social and Environmental Risk Factors on Pregnancy Outcomes: The LEAP Study.

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.

Long-term exposure to air pollution and hospitalization for dementia in the Rome longitudinal study.

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, NO2) and particulate matter (PM) and a chemical transport model for ozone (O3). 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 NO2 (10 µg/m3) and dementia hospitalizations (HR = 0.97; 95% CI: 0.96-0.99) and a positive association between exposure to O3, NOx and dementia hospitalizations, (O3: HR = 1.06; 95% CI: 1.04-1.09 per 10 µg/m3; NOx: HR = 1.01; 95% CI: 1.00-1.02 per 20 µg/m3).H. Exposure to NOx, NO2, PM2.5, and PM10 was positively associated with Vd and negatively associated with Ad. Hospitalization for Sd was positively associated with exposure to O3 (HR = 1.20; 95% CI: 1.15-1.24 per 10 µg/m3). CONCLUSIONS: Our results showed a positive association between exposure to NOx and O3 and hospitalization for dementia and a negative association between NO2 exposure and hospitalization for dementia. In the analysis by subtype, exposure to each pollutants (except O3) demonstrated a positive association with vascular dementia, while O3 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.

Exposure to Residential Greenness as a Predictor of Cause-Specific Mortality and Stroke Incidence in the Rome Longitudinal Study.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Air pollution and occurrence of type 2 diabetes in a large cohort study.

The few cohort studies that have investigated the association between exposure to air pollution and occurrence of diabetes have reported conflicting results. We aimed to evaluate the association of long-term exposure to particulate matter (PM), nitrogen oxides (NOx) and ozone (O3), with baseline prevalence and incidence of type 2 diabetes in a large administrative cohort in Rome, Italy. A total of 1,425,580 subjects aged 35+years (January 1st, 2008) were assessed and followed for six years. We estimated PM10, PM2.5-10, PM2.5, NO2, and NOx exposures at residence using land use regression models, and summer O3 exposure using dispersion modeling. To estimate the association between air pollutant exposures and prevalence and incidence of diabetes, we used logistic and Cox regression models, considering individual, environmental (noise and green areas), and contextual characteristics. We identified 106,387 prevalent cases at baseline and 65,955 incident cases during the follow-up period. We found positive associations between nitrogen oxides exposures and prevalence of diabetes with odds ratios (ORs) up to 1.010 (95% CI: 1.002, 1.017) and 1.015 (1.009, 1.021) for NO2 and NOx, respectively, per fixed increases (per 10µg/m3 and 20µg/m3, respectively). We also found some evidence of an association between NOx and O3 and incidence of diabetes, with hazard ratios (HRs) of 1.011 (95%CI: 1.003-1.019) and 1.015 (1.002-1.027) per 20 and 10µg/m3 increases, respectively. The association with O3 with incident diabetes was stronger in women than in men and among those aged <50years. In sum, long-term exposure to nitrogen oxides was associated with prevalent diabetes while NOx and O3 exposures were associated with incident diabetes.

Effects of long-term exposure to particulate matter and metal components on mortality in the Rome longitudinal study.

BACKGROUND: The effect of long-term exposure to metal components in particulate matter on mortality are still controversial. OBJECTIVES: To study the association between long-term exposure to PM10, PM2.5, PM2.5 absorbance, particulate matter components (copper, iron, zinc, sulfur, silicon, potassium, nickel, and vanadium) and non-accidental, cardiovascular (CVD), and ischemic heart disease (IHD) mortality. METHODS: All 30+ year olds from the Rome Longitudinal Study were followed for vital status from October 2001 until December 2010. We used land use regression models to estimate annual average concentrations at residences and Cox models to estimate the associations between pollutants and cause-specific mortality, adjusting for individual and contextual characteristics. Hazard ratios (HRs) were expressed per increments equal to the 5th-95th percentile range of each pollutant distribution. RESULTS: We analyzed 1,249,108 residents and found strong associations between all exposure indicators and mortality. We observed higher mortality risk with increasing exposure to PM2.5 absorbance (HR=1.05; 95% CI: 1.03-1.06) and to tracers of non-tailpipe traffic emissions such as tire and brake wear (Cu, Fe, and Zn); for PM2.5Zn, we found HR=1.06 (95% CI: 1.04-1.08) for non-accidental mortality, HR=1.07 (95% CI: 1.04-1.10) for CVD, and HR=1.11 (95% CI: 1.06-1.16) for IHD mortality. With increasing levels of nickel in PM10, we found HR=1.07 (95% CI: 1.05-1.09) for non-accidental mortality, HR=1.08 (95% CI: 1.05-1.11) for CVD, and HR=1.13 (95% CI: 1.08-1.18) for IHD mortality. Results were robust when we adjusted for PM mass and for cardiovascular mortality when we adjusted for NO2. CONCLUSIONS: In addition to vehicular exhaust pollutants, PM related to non-tailpipe emissions and mixed oil burning/industry plays an important role in mortality.