COVID-19 impact on the decision process of the Italian Medicine Agency: a quantitative assessment.

Background: Since the COVID-19 pandemic has placed more attention on drugs' approval process and the importance of rapid decision-making in the healthcare sector, it is crucial to assess how time to market (TTM) of drugs varied. Objective: To estimate the impact of the COVID-19 pandemic on TTM of drugs in Italy. Methods: An IQVIA database was used to retrieve information on drugs that obtained positive opinion from the Committee for Medicinal Products for Human Use between January 2015 and December 2021. The available observations were divided into three groups (Pre COVID, Partially COVID, and Fully COVID) according to the timing of their negotiation process. Differences in average TTM among the three groups were analyzed in three steps: (1) descriptive statistics; (2) univariate analysis; (3) multivariate analysis, using a matching estimator. Results: A total of 363 unique combinations of molecule and indication met the inclusion criteria: 174 in the Pre COVID group, 69 in the Partially COVID group, and 123 in the Fully COVID group. Descriptive statistics and univariate analysis found a statistically significant difference in TTM among the three periods, with average TTM increasing during the pandemic (+136 days, p = 0.00) and then decreasing afterward (-23 days, p = 0.09). In the matching analysis, results for the Partially COVID period were confirmed (+108 days, p = 0.00) while results for the Fully COVID period lost significance but maintained a negative sign. Conclusions: The results suggest that after an adjustment phase in the Partially COVID period, a return to the status quo was reached.

Incidence of ventricular arrhythmias related to COVID infection and vaccination in patients with Brugada syndrome: Insights from a large Italian multicenter registry based on continuous rhythm monitoring.

INTRODUCTION: Brugada syndrome (BrS) has a dynamic ECG pattern that might be revealed by certain conditions such as fever. We evaluated the incidence and management of ventricular arrhythmias (VAs) related to COVID-19 infection and vaccination among BrS patients carriers of an implantable loop recorder (ILR) or implantable cardioverter-defibrillator (ICD) and followed by remote monitoring. METHODS: This was a multicenter retrospective study. Patients were carriers of devices with remote monitoring follow-up. We recorded VAs 6 months before COVID-19 infection or vaccination, during infection, at each vaccination, and up to 6-month post-COVID-19 or 1 month after the last vaccination. In ICD carriers, we documented any device intervention. RESULTS: We included 326 patients, 202 with an ICD and 124 with an ILR. One hundred and nine patients (33.4%) had COVID-19, 55% of whom developed fever. Hospitalization rate due to COVID-19 infection was 2.76%. After infection, we recorded only two ventricular tachycardias (VTs). After the first, second, and third vaccines, the incidence of non-sustained ventricular tachycardia (NSVT) was 1.5%, 2%, and 1%, respectively. The incidence of VT was 1% after the second dose. Six-month post-COVID-19 healing or 1 month after the last vaccine, we documented NSVT in 3.4%, VT in 0.5%, and ventricular fibrillation in 0.5% of patients. Overall, one patient received anti-tachycardia pacing and one a shock. ILR carriers had no VAs. No differences were found in VT before and after infection and before and after each vaccination. CONCLUSIONS: From this large multicenter study conducted in BrS patients, followed by remote monitoring, the overall incidence of sustained VAs after COVID-19 infection and vaccination is relatively low.

Electrocardiographic Approach to Atrial Flutter: Classifications and Differential Diagnosis.

Atrial flutter (AFL) is a macro-reentrant arrhythmia characterized, in a 12 lead ECG, by the continuous oscillation of the isoelectric line in at least one lead. In the typical form of AFL, the oscillation is most obvious in the inferior leads, due to a macro-reentrant circuit localized in the right atrium, with the cavo-tricuspid isthmus as a critical zone.: This circuit can be activated in a counterclockwise or clockwise direction generating in II, III, and aVF leads, respectively, a slow descending/fast ascending F wave pattern (common form of typical AFL) or a balanced ascending/descending waveform (uncommon form of typical AFL). Atypical AFLs (scar-related) do not include the CTI in the circuit and show an extremely variable circuit location and ECG morphology.

Multivariate tools to investigate the spatial contaminant distribution in a highly anthropized area (Gulf of Naples, Italy).

The Gulf of Naples located in a high anthropized coastal area is subjected to an infrastructural intervention for the installation of a submarine power pipeline. In order to evaluate the distribution of contaminants in the seafloor sediments, a preliminary study has been conducted in the area using multivariate techniques. The statistic approach was performed to gain insights on the occurrence of organic and inorganic contaminants within the area, aiming to identify the relevant hot spots. Three geographical sub-areas influenced by different contaminant association were recognized: Torre Annunziata (TA), Capri (CA), and middle offshore (MO). TA and CA resulted marked by a severe contamination pattern due to anthropogenic pressures. In addition, the influence of the depositional basin in governing the contamination trend has been pointed out. The supervised technique PLS_DA resulted to be a powerful tool in addressing the complexity of the huge dataset acquired during the marine survey, highlighting the main trends in the variability of quality indicators, orienting thus the deeper investigations during follow-up monitoring activities.

Habitat heterogeneity: A confounding factor for the effect of pollutants on macrobenthic community in coastal waters.

Discrepancies were found between Ecological Status of sediments evaluated though the analysis of macrobenthic community and chemical analyses along a heavily trafficked and contaminated maritime seaway in Tyrrhenian Sea. Chemical analyses showed some sites highly contaminated by PAHs and metals with values exceeding thresholds for Good Chemical status and representing potential toxicological risk for benthic animals. Conversely, macrobenthic communities were highly rich and diverse, with Ecological Status (through M-AMBI) Good and High at each site. Sampling depth, total organic carbon, and total nitrogen were the major factors influencing biotic indices (AMBI, M-AMBI, S, H), even if concentrations of PAHs and metals (V, As, and Fe) contributed in explaining a part of indices variability. Habitat heterogeneity of sampled sites is likely acting as a confounding factor for two reasons: (1) high variability of environmental parameters leads to high richness and diversity, to which M-AMBI is sensitive, and (2) environmental parameters explained part of the variability of indices, together with contaminants. Our results suggested the importance of considering natural variability as a fundamental step of environmental impact assessment, for the correct interpretation of biotic indices.

Types, occurrence and distribution of microplastics in sediments from the northern Tyrrhenian Sea.

This is the first survey to investigate microplastic contamination in the Northern Tyrrhenian seafloor, along a 31 km-long transect from the port of Piombino (Tuscany) to the port of Portoferraio (Elba Island). Plastics extracted from 58 sediment samples were counted and identified by Fourier-transform infrared spectroscopy (FTIR). Plastic pollution occurred in sites closer to ports as well as in offshore stations. Microplastics (1-5 mm) accounted for over 80% of particles. For all samples, the dominant microplastic type was filaments, followed by fragments and films. Six polymers were identified: nylon, polyurethane, polyethylene, and polyethylene terephtalate were the most common. This part of the Tyrrhenian Sea is a busy shipping route connecting the mainland to the Elba Island, with thousands cargo and passenger ships passing by per year. Our data constitute a baseline for microplastic research in the Tyrrhenian seafloor.

Is the microplastic selective according to the habitat? Records in amphioxus sands, Mäerl bed habitats and Cymodocea nodosa habitats.

This study estimated for the first time the total loads of plastic litter (macro- meso- and micro-plastics) in sediments of different habitat types from the Northern Adriatic Sea. Samples were collected in March 2016. The sampling sites were settled in shoreline, on the C. nodosa bottoms, Amphioxus sands, and Mäerl bed habitats. Microplastics items were present in all sampling site and ranging within 137-703 items/kg d.w. from Mäerl bed habitat to the shoreline. In C. nodosa bottoms 170 items/kg d.w. were found, while in Amphioxus sands were recorded on average 194 items/kg d.w. Due to the absence of statistical associations among litter levels and abundance of B. lanceolatum in the study area, this research present the needs to develop a new method and more research to for the evaluation of how much the interrelation between sensible habitats and microplastic exist.

Small plastic debris in sediments from the Central Adriatic Sea: Types, occurrence and distribution.

This is the first survey to investigate the occurrence and extent of microplastic contamination in sediments collected along a coast-open sea 140km-long transect in the Central Adriatic Sea. Plastic debris extracted from 64 samples of sediments were counted, weighted and identified by Fourier-transform infrared spectroscopy (FT-IR). Several types of plastic particles were observed in 100% of the stations. Plastic particles ranged from 1 to 30mm in length. The primary shape types by number were filaments (69.3%), followed by fragments (16.4%), and film (14.3%). Microplastics (1-5mm) accounted for 65.1% of debris, mesoplastics (5-20mm) made up 30.3% of total amount, while macro debris (>20mm) accounted for 4.6% of total plastics collected. Identification through FT-IR spectroscopy evidenced the presence of 6 polymer types: the majority of plastic debris were nylon, polyethylene and ethylene vinyl alcohol copolymer. Our data are a baseline for microplastic research in the Adriatic Sea.