Quantitative EEG analysis of brivaracetam in drug-resistant epilepsy: A pharmaco-EEG study.

OBJECTIVE: Brivaracetam (BRV) is a recent antiseizure medication (ASM) approved as an add-on therapy for people with focal epilepsy. BRV has a good efficacy and safety profile compared to other ASMs. However, its specific effects on resting-state EEG activity and connectivity are unknown. The aim of this study is to evaluate quantitative EEG changes induced by BRV therapy in a population of adult people with drug-resistant epilepsy (PwE) compared to healthy controls (HC). METHODS: We performed a longitudinal, retrospective, pharmaco-EEG study on a population of 23 PwE and a group of 25 HC. Clinical outcome was dichotomized into drug-responders (i.e., >50% reduction in seizures' frequency; RES) and non-responders (N-RES) after two years of BRV. EEG parameters were compared between PwE and HC at baseline (pre-BRV) and after three months of BRV therapy (post-BRV). We investigated BRV-related variations in EEG connectivity using the phase locking value (PLV). RESULTS: BRV therapy did not induce modifications in power spectrum density across different frequency bands. PwE presented lower PLV connectivity values compared to HC in all frequency bands. RES exhibited lower theta PLV connectivity compared to HC before initiating BRV and experienced an increase after BRV, eliminating the significant difference from HC. CONCLUSIONS: This study shows that BRV does not alter the EEG power spectrum in PwE, supporting its favourable neuropsychiatric side-effect profile, and induces the disappearance of EEG connectivity differences between PwE and HC. SIGNIFICANCE: The integration of EEG quantitative analysis in epilepsy can provide insights into the efficacy, mechanism of action, and side effects of ASMs.

Causal impact evaluation of occupational safety policies on firms' default using machine learning uplift modelling.

It is often undermined that occupational safety policies do not only displace a direct effect on work well-being, but also an indirect effect on firms' economic performances. In such context, econometric models dominated the scenes of causality until recently while Machine Learning models were seen with skepticism. With the rise of complex datasets, an ever-increasing need for automated algorithms capable to handle complex non-linear relationships between variables has brought to uncover the power of Machine Learning for causality. In this paper, we carry out an evaluation of a public aid-scheme implemented in Italy and oriented to support investment of small and medium enterprises (SMEs) in occupational safety and health (OSH) for assessing the impact on the survival of corporations. A comparison of thirteen models is performed and the Individual Treatment Effect (ITE) estimated and validated based on the AUUC and Qini score for which best values of 0.064 and 0.407, respectively, are obtained based on the Light Gradient Boosting Machine (LightGBM). An additional in-depth statistical analysis also revealed that the best beneficiaries of the policy intervention are those firms that experience performance issues in the period just before the interventions and for which the increased liquidity brought by the policy may have prevented default.

Ten-year outcomes after off-pump and on-pump coronary artery bypass grafting: an inverse probability of treatment weighting comparative study.

AIMS: The debate on the advantages and limitations of off-pump myocardial revascularization (OPCAB) on long-term outcomes has not still arrived to a conclusion. This study was designed to compare the impact of OPCAB vs, on-pump coronary artery bypass grafting (CABG) on long-term mortality and major adverse cardiac and cerebrovascular events (MACCEs). METHODS: The PRIORITY project was designed to evaluate the long-term outcomes of two large prospective multicenter cohort studies on CABG. Data on isolated CABG were linked to two administrative datasets. The inverse probability of treatment weight was employed to balance the treatment groups. Time-to-event methods were employed to analyze endpoints. RESULTS: The cohort consisted of 10 988 patients who underwent isolated CABG (27.2% OPCAB). The median follow-up time was 7.9 years and was 100% complete. Unadjusted long-term survival was significantly worst for OPCAB, confirmed by weighted models (hazard ratio 1.08, 95% confidence interval (CI) 1.01-1.14, P = 0.01). OPCAB was associated to an increased risk of MACCE at 10 years (weighted hazard ratio 1.18, 95% CI 1.12-1.23, P < 0.001). Inside the MACCEs, OPCAB was significantly related to increased incidence of repeat revascularization (hazard ratio 2.27, 95% CI 1.39-3.85, P < 0.001, in the first 6 months, hazard ratio 1.19, 95% CI 1.09-1.32, P < 0.001 afterward) and stroke (hazard ratio 1.22, 95% CI 1.10-1.35, P < 0.001). CONCLUSION: The results of this study suggest that OPCAB was associated with an increased risk of mortality, repeat myocardial revascularization and stroke at 10 years compared with on-pump CABG.

[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 gender on 10-year outcome after coronary artery bypass grafting.

OBJECTIVES: Our goal was to evaluate the impact of gender on the 10-year outcome of patients after isolated coronary artery bypass grafting (CABG) included in the Italian nationwide PRedictIng long-term Outcomes afteR Isolated coronary arTery bypass surgery (PRIORITY) study. METHODS: The PRIORITY project was designed to evaluate the long-term outcomes of patients who underwent CABG and were included in 2 prospective multicentre cohort studies. The primary end point of this analysis was major adverse cardiac and cerebrovascular events. Baseline differences between the study groups were balanced with propensity score matching and inverse probability of treatment. Time to events was analysed using Cox regression and competing risk analysis. RESULTS: The study population comprised 10 989 patients who underwent isolated CABG (women 19.6%). Propensity score matching produced 1898 well-balanced pairs. The hazard of major adverse cardiac and cerebrovascular event was higher in women compared to men [adjusted hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.03-1.23; P = 0.009]. The incidence of major adverse cardiac and cerebrovascular event in women was significantly higher at 1 year (HR 1.31, 95% CI 1.11-1.55; P < 0.001) and after 1 year (HR 1.11, 95% CI 1.00-1.24; P = 0.05). Mortality at 10 years in the matched groups was comparable (HR 1.04, 95% CI 0.93-1.16; P = 0.531). Women have significantly a higher 10-year risk of myocardial infarction (adjusted HR 1.40, 95% CI 1.17-1.68; P = 0.002) and percutaneous coronary intervention (adjusted HR 1.32, 95% CI 1.10-1.59; P = 0.003). CONCLUSIONS: The present study documented an excess of non-fatal cardiac events after CABG among women despite comparable 10-year survival with men. These findings suggest that studies investigating measures of tertiary prevention are needed to decrease the risk of adverse cardiovascular events among women.

[The PRIORITY study - PRedictIng long term Outcomes afteR Isolated coronary arTery bypass surgerY]. / Lo studio PRIORITY - PRedictIng long term Outcomes afteR Isolated coronary arTery bypass surgerY.

The allocation of clinical and economic resources is an emerging issue in health management. A useful update necessarily depends on the evaluation of long-term outcomes of clinical and surgical resources that can permit emphasis on all amendable fields, improve quality of care, and reduce health costs. The PRIORITY (PRedictIng long term Outcomes afteR Isolated coronary arTery bypass surgerY) study represents the first innovative step toward the updating of health management in a selected field, surgery for coronary artery disease, which is one of the most prevalent diseases and requires allocation of high-cost resources, although information on long-term outcomes is limited. The aims of the PRIORITY study are the identification of preoperative risk factors for long-term outcomes and the development of clinical and administrative preoperative scores that can guide clinicians and the national health system to more appropriate actions for increasing quality of care and reducing costs.

The concept of species and the foundations of biology, a case study: the Callithrix jacchus group (Primates-Platyrrhini).

The axiomatic theory presented in Galleni and Forti [1999], being part of the foundational programme of Ennio De Giorgi, is based on the fundamental notions of quality, relation, operation and collection, and provides a very general axiomatization of the biological notions of living object, generation, species and speciation. Within this theoretical framework we consider here a difficult case of classification of species: the Callithrix jacchus group of the New World monkeys. Although the morphological analysis strongly suggests the individuation of six different species, nevertheless several experiments of crossing give evidence to fertility of hybrids. Since both the morphological and the hybridological criteria have shown to be of enormous importance in actual classification of species, this apparent contradiction seems very disappointing. Our axiomatization of speciation processes as operations acting in special time intervals permits to avoid the contradiction by allowing for individuals which, during such special periods, may belong to more than one species. Therefore we assume that one or more speciation processes are developing, starting from a unique protospecies and differentiating in six new ones. In order to obtain more evidence of these processes, new observations and suitable experiments are needed.