Circular economy, stock volatility, and resilence to the COVID-19 shock: evidence from European companies

Background. By decoupling economic growth from an intensive use of resources, preventing the impairment of natural capital, and enhancing resilience to system-wide shocks, Circular Economy (CE) is a powerful opportunity to hedge against “linear” risk factors. In fact, it helps shielding against the risk of assets becoming stranded, can generate fresh and non-speculative demand for investments, and can improve investment results at both individual and portfolio level. Problem. Therefore, equity investors into circular undertakings could benefit from (H1) reduced stock return volatility, as well as (H2) a greater ability to withstand exogenous negative events. Approach. For testing these hypotheses, we constructed a sample of 644 listed companies across EU-15 countries, plus Switzerland, and 17 different industries. We retrieved their market data in 2019-20, as well as their accounting fundamentals in 2018-19. By controlling for the latter, we investigated whether equity risk — either in total terms (i.e., the standard deviation of returns) or circumscribed to the systematic component thereof (i.e., the Beta against a European or global market index) — may be explained by a company’s degree of circularity, measured by the Circularity Score (CS). This is a novel indicator originally proposed by Zara and Ramkumar (2022), based on Refinitiv ESG data, the methodology whereof we significantly amended. As a core innovation, in weighting an entity’s performance on a CE framework, we assessed the latter’s ‘financial materiality’ (i.e., relevance to the company’s business) at sub-industry level, applying the SASB Materiality Maps. Via OLS estimation, we tested our hypotheses (i) over the whole-time horizon, in a panel model; (ii) on specific timeframes, in a standard cross-sectional model. The latter was applied to either the entire 2020 or subperiods thereof: namely, with respect to the COVID-19 outbreak, we distinguished between a pre-shock, a shock and a post-shock phase. Our quest was refined to conduct a deeper investigation into the Oil & Gas industry, which is intrinsically the most exposed to linear risks and, also, did experience the widest volatility in 2020. Findings. Both H1 and H2 received widespread confirmation. The CS was found to exert a negative, significant and robust effect on all the three risk measures, over the whole timespan as well as in subperiods (particularly the post-shock phase). Also, amplifying effects were recorded as of the Oil & Gas industry. Conclusions. Our results lend remarkable support to the idea that the CE is a powerful enabler of de-risking, also in case of a severe shock, with a view to mitigating the negative consequences and building back better. They call on firms and policymakers to foster the circular transition, thereby accelerating economic recovery in the aftermath of the pandemic crisis

Laparoscopy for relapsing paralytic ileus in multiple sclerosis: a video case report

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Calcitonin gene-related peptide antagonists in pregnancy: a disproportionality analysis in VigiBase®

Background Current evidence on the safety of calcitonin gene–related peptide antagonists (CGRP-A) in pregnancy for the treatment of both episodic and chronic migraine is scarce and does not yet provide definitive information. By querying VigiBase$^{®}$, the World Health Organization global pharmacovigilance database, this study aimed to detect differences in the reporting frequency between CGRP-A and triptans in relation to pregnancy. Methods Disproportionality analyses on de-duplicated safety reports collected in VigiBase$^{®}$ as of 31.05.2023 reporting exposure to CGRP-A in pregnancy with or without pregnancy outcomes. A Reporting Odds Ratio (ROR) with a 95% confidence interval (CI) was used as a measure of disproportionality and the threshold for the detection of a signal of disproportionate reporting was set with a 95% CI lower limit > 1. Findings Four hundred sixty-seven safety reports reported exposure to CGRP-A in pregnancy, mostly originating from the United States of America (360/467, 77%), more frequently reported by patients (225/467, 48%), who were mainly females (431/467, 92%), and more frequently reported exposure to CGRP-A during pregnancy (400/467, 86%). Compared to triptans, no signals of disproportionate reporting were detected with CGRP-A either for the overall reporting of pregnancy-related safety reports (ROR 0.91, 95% CI 0.78–1.06), for the reporting of pregnancy outcomes (maternal and/or foetal/neonatal, ROR 0.54, 95% CI 0.45–0.66), or for the reporting of foetal/neonatal outcomes (ROR 0.53, 95% CI 0.41–0.68). Conclusions This study showed that, to date, there are no signals of increased reporting with CGRP-A compared to triptans in relation to pregnancy in VigiBase$^{®}$. Future pharmacovigilance studies are needed to confirm these findings

Safety profile of monoclonal antibodies targeting the calcitonin gene-related peptide system in pregnancy: Updated analysis in VigiBase®

Background: Safety data on the use of migraine preventive monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) system in pregnancy are limited. Methods: Updated pharmacovigilance assessment of the safety reports related to pregnancy associated with erenumab, galcanezumab, fremanezumab and eptinezumab, retrieved from VigiBase® as of 31 December 2021. As primary outcome, the whole group of monoclonal antibodies targeting the CGRP system was considered and sex and age subgroup disproportionality analyses using the reporting odds ratio (ROR) were conducted. Results: 286 safety reports were found: 116 (40.6%) on erenumab, 125 (43.7%) on galcanezumab, 39 (13.6%) on fremanezumab, 6 (2.1%) on eptinezumab. One hundred and forty-nine (52.1%) safety reports reported only drug exposure in relation to pregnancy while 137 (47.9%) also included ≥1 pregnancy outcomes: maternal outcomes (n = 64), spontaneous abortion (n = 63), foetal growth restriction (n = 1), prematurity (n = 8), neonatal outcomes (n = 13), and poor breastfeeding (n = 1). No specific patterns of maternal, foetal and neonatal toxicity were observed. Spontaneous abortion was not disproportionally more frequently reported with erenumab, galcanezumab, fremanezumab and eptinezumab compared with the entire database (ROR 1.1, 95% confidence interval, CI, 0.8–1.5), the entire database since 2018 (ROR 1.3, 95% CI 1.0–1.8), and triptans (ROR 1.2, 95% CI 0.8–1.9). Conclusions: This updated safety analysis on erenumab, galcanezumab, fremanezumab and eptinezumab in pregnancy showed no signals of foeto-maternal toxicity according to VigiBase® safety reports

New Approaches and Technologies to Improve Accuracy of Acute Otitis Media Diagnosis

: Several studies have shown that in recent years incidence of acute otitis media (AOM) has declined worldwide. However, related medical, social, and economic problems for patients, their families, and society remain very high. Better knowledge of potential risk factors for AOM development and more effective preventive interventions, particularly in AOM-prone children, can further reduce disease incidence. However, a more accurate AOM diagnosis seems essential to achieve this goal. Diagnostic uncertainty is common, and to avoid risks related to a disease caused mainly by bacteria, several children without AOM are treated with antibiotics and followed as true AOM cases. The main objective of this manuscript is to discuss the most common difficulties that presently limit accurate AOM diagnosis and the new approaches and technologies that have been proposed to improve disease detection. We showed that misdiagnosis can be dangerous or lead to relevant therapeutic mistakes. The need to improve AOM diagnosis has allowed the identification of a long list of technologies to visualize and evaluate the tympanic membrane and to assess middle-ear effusion. Most of the new instruments, including light field otoscopy, optical coherence tomography, low-coherence interferometry, and Raman spectroscopy, are far from being introduced in clinical practice. Video-otoscopy can be effective, especially when it is used in association with telemedicine, parents' cooperation, and artificial intelligence. Introduction of otologic telemedicine and use of artificial intelligence among pediatricians and ENT specialists must be strongly promoted in order to reduce mistakes in AOM diagnosis

Fatigue, sleepiness and depression in multiple sclerosis: defining the overlaps for a better phenotyping.

BACKGROUND AND OBJECTIVES To define the boundaries and the overlaps between fatigue, sleepiness and depression in patients with multiple sclerosis (MS) by using different tools for each dimension, including instrumental sleep analysis. METHODS In this cross-sectional, observational study, 71 MS patients (males/females: 20/51; mean age: 48.9 ± 10.5 years) filled in clinical questionnaires and performed polysomnography followed by maintenance of wakefulness test (MWT). Frequency and reciprocal overlap of sleepiness, fatigue and depression in MS were expressed by Eulero-Venn diagrams; standard multiple regression was used to assess the ability of symptoms to predict each other. RESULTS There was a high percentage of fatigued (70%), somnolent (45%) and depressed (27%) patients. Fatigue had the strongest overlap and correlated with both depression (beta: 0.52, p < 0.001) and sleepiness (beta: 0.74, p < 0.001). Somnolence and depression were nearly always accompanied by fatigue and were well differentiated from each other by MWT. Four MS subgroups were identified that had: (1) fatigue only; (2) fatigue and sleepiness (3) fatigue and depression; (4) fatigue, sleepiness and depression. DISCUSSION The subjective and objective tools are not able to clearly distinguish fatigue from sleepiness and depression, while only a test of vigilance can be helpful in separating somnolence and depression from each other

Treatment satisfaction, adherence and behavioral assessment in patients de – escalating from natalizumab to interferon beta

Background: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a possible treatment option in multiple sclerosis (MS) patients interrupting NTZ because of increased risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to evaluate satisfaction and adherence to treatment, behavioral and fatigue changes in patients switched to IFN B 1B compared to continued NTZ treatment. Methods: A 1 year, prospective, randomized, rater-blinded, parallel-group study. Nineteen relapsing remitting (RR) MS patients, randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment, who had previously received NTZ for at least 12 months with disease stability and fearing or at risk for PML were included. Patients underwent behavioral and treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral assessment included measures of cognition, fatigue and quality of life. Treatment assessment included measures of satisfaction, persistence and adherence to treatment. Clinical-radiological disease activity and safety were also assessed. Results: Baseline characteristics of patients were similar between groups except for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04). Within-group comparisons at the three time points, as well as interaction analysis of treatment effect over time did not show any statistically significant differences in behavioral or treatment assessments, but a coherent trend favoring NTZ over IFN B 1B. Conclusions: De-escalating NTZ to IFN B 1B is feasible and associated with overall good patient related outcome and persistently stable behavioral measures

Interferon beta 1b following natalizumab discontinuation: one year, randomized, prospective, pilot trial

Background: Natalizumab (NTZ) discontinuation leads to multiple sclerosis reactivation. The objective of this study is to compare disease activity in MS patients who continued on NTZ treatment to those who were switched to subcutaneous interferon 1b (IFNB) treatment. Methods: 1-year randomized, rater-blinded, parallel-group, pilot study (ClinicalTrial.gov ID: NCT01144052). Relapsing remitting MS patients on NTZ for ≥12 months who had been free of disease activity on this therapy (no relapses and disability progression for ≥6 months, no gadolinium-enhancing lesions on baseline MRI) were randomized to NTZ or IFNB. Primary endpoint was time to first on-study relapse. Additional clinical, MRI and safety parameters were assessed. Analysis was based on intention to treat. Results: 19 patients (NTZ n=10; IFNB n=9) with similar baseline characteristics were included. 78% of IFNB treated patients remained relapse free (NTZ group: 100%), and 25% remained free of new T2 lesions (NTZ group: 62.5%). While time to first on-study relapse was not significantly different between groups (p=0.125), many secondary clinical and radiological endpoints (number of relapses, proportion of relapse free patients, number of new T2 lesions) showed a trend, or were significant (new T2 lesions at month 6) in favoring NTZ. Conclusions: De-escalation therapy from NTZ to IFNB over 1 year was associated with some clinical and radiological disease recurrence. Overall no major safety concerns were observed