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Disproportionality analyses are the most-commonly used study design used in the post-marketing phase to detect suspected adverse drug reactions in individual case safety reports. Recent years have witnessed an exponential increase in published articles on disproportionality analyses, thanks to publicly accessible databases. Unfortunately, this trend was accompanied by concerns on lack of transparency and misinterpretation of results, both generating unjustified alarm and diluting true signals into overwhelming noise. The READUS-PV guideline for reporting disproportionality analysis was developed to tackle this emerging issue. In this perspective article, we describe the rationale behind the development of the READUS-PV guideline, the first collaborative initiative to harmonize the reporting of disproportionality analyses. The adoption of the checklists will assist researchers, regulators, and reviewers in the reporting, assessment, and publication of disproportionality analyses. Acknowledging the challenges ahead of effective implementation, we advocate for a global endorsement by Pharmacology Journals. A wide dissemination of the READUS-PV guideline is crucial to foster transparency and reproducibility of pharmacovigilance research, supporting an effective exploitation of disproportionality analysis among other irreplaceable post-marketing research tools to ensure drug safety.

Background To date, evidence on late-onset immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) is limited to a small number of clinical cases. This study aimed to identify drug- and patient-related characteristics potentially associated with the reporting of late-onset irAEs with ICIs in VigiBase, the WHO global database of individual case safety reports (ICSRs).Methods Observational study comparing deduplicated ICSRs with ICIs reporting late-onset irAEs (occurred >90 days after ICI discontinuation) versus ICSRs with ICIs not reporting late-onset irAEs, collected in VigiBase from 2011 to December 31, 2022. Logistic regression was used to model the relationship between drug-related and patient-related characteristics of ICSRs and the reporting of late-onset irAEs. Significance was determined for variables with the lower bound of the 95% CI of the reporting OR (ROR) higher than 1 and a p value

Key Clinical Message Symmetrical drug‐related intertriginous and flexural exanthema, commonly known as “baboon syndrome” due to its typical involvement of the gluteal area, is an erythematous symmetrical rash associated with systemic drug administration.

COVID-19 Acute Respiratory Distress Syndrome (CARDS) is the most serious complication of COVID-19. The SARS-CoV-2 outbreaks rapidly saturated intensive care unit (ICU), forcing the application of non-invasive respiratory support (NIRS) in respiratory intermediate care unit (RICU). The primary aim of this study is to compare the patients’ clinical characteristics and outcomes (Helmet-Continuous Positive Airway Pressure (H-CPAP) success/failure and survival/death). The secondary aim is to evaluate and detect the main predictors of H-CPAP success and survival/death. A total of 515 patients were enrolled in our observational prospective study based on CARDS developed in RICU during the three Italian pandemic waves. All selected patients were treated with H-CPAP. The worst ratio of arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) PaO2/FiO2 during H-CPAP stratified the subjects into mild, moderate and severe CARDS. H-CPAP success has increased during the three waves (62%, 69% and 77%, respectively) and the mortality rate has decreased (28%, 21% and 13%). H-CPAP success/failure and survival/death were related to the PaO2/FiO2 (worst score) ratio in H-CPAP and to steroids’ administration. D-dimer at admission, FiO2 and positive end expiratory pressure (PEEP) were also associated with H-CPAP success. Our study suggests good outcomes with H-CPAP in CARDS in RICU. A widespread use of steroids could play a role.

Introduction: This paper aims to explore the positive correlation between practicing yoga and meditation at school and an increase in academic performance with a reduction in states of anxiety and stress. Research Aim: The systematic review aims to confirm the theory that the practice of yoga and meditation is beneficial for children and can help them in the school context. Evidence-based Facts: Ten articles were carefully analyzed to find out which yoga and meditation techniques were most used and what benefits they brought in developmental age. Thanks to breathing techniques and meditation, studies indicate that children learn to recognize their emotions and strategies to manage them in the best way. Summary: Protocols demonstrate that there are positive correlations between practicing yoga and meditation at school and a decrease in stress levels and an increase in attention span and memory. These benefits help children improve their academic performance, develop greater balance and flexibility, and avoid bad postures.

Spontaneous reporting systems remain pivotal for post-marketing surveillance and disproportionality analysis (DA) represents a recognized approach for early signal detection. Although DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient, their role remain irreplaceable for rapid detection of rare and unpredictable adverse drug reactions with strong drug-attributable component (e.g., designated medical events), especially when developed by a multidisciplinary team and combined with a careful case-by-case analysis (individual inspection of reports for causality assessment or to uncover reporting patterns and clinical features). In the recent past, a remarkable increase in publications of pharmacovigilance studies using DAs was observed, albeit the quality was debated: several publications contained “spin”, namely, misinterpretation of results to infer causality, calculate incidence, or provide risk stratification, which may ultimately result in unjustified alarm. The development of dedicated Guidelines by the international READUS-PV project (https://readus-statement.org/) will allow reproducible and transparent publication of accurate DAs, thus supporting their real transferability and exploitation by regulators and clinicians. This review offered a perspective on methodological aspects (and understanding) of DAs, their rationale, design, reporting, and interpretation.

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS).Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–December 2022) were identified through the preferred term “pericarditis.” Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero.Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25–65 years.Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.

Abstract Background As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. Methods A retrospective, pharmacovigilance study of the FDA’s global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (

Abstract Background Lateral ankle sprain (LAS) is a common and burdensome injury. However, the quality of its management is scant. Nowadays, physiotherapy management of musculoskeletal diseases seems to be generally not based on research evidence. Studies that investigated the knowledge-to-practice gap in LAS management are yet to be carried out. Therefore, this research investigated physiotherapists’ knowledge of and adherence to LAS Clinical Practice Guidelines (CPGs) and recommendations. Methods A cross-sectional study based on an online survey structured in three sections. The first section collected demographic data. The second section showed two clinical cases (with positive and negative Ottawa Ankle Rules (OAR), respectively). The participants indicated which treatments they would adopt to manage them. Participants were classified as ‘following’, ‘partially following’, ‘partially not following’ and ‘not following’ the CPGs and recommendations. In the third section, participants expressed their agreement with different CPG and recommendation statements through a 1-5 Likert scale. Results In total, 483 physiotherapists (age: 34 ± 10; female 38%, male 61.5%, other 0.5%) answered the survey: 85% completed the first two sections, 76% completed all three sections. In a case of acute LAS with negative OAR, 4% of the participants were considered as ‘following’ recommended treatments, 68% as ‘partially following’, 23% as ‘partially not following’, and 5% as ‘not following’. In a case of acute LAS with positive OAR, 37% were considered ‘following’ recommended treatments, 35% as ‘partially following’, and 28% as ‘not following’. In the third section, the consensus was achieved for 73% of the statements. Conclusion This study showed that although there is a good knowledge about first-line recommended treatments, a better use of CPGs and recommendations should be fostered among physiotherapists. Our results identify an evidence-to-practice gap in LAS management, which may lead to non-evidence-based practice behaviors.

Safety data on MET inhibitors in patients with advanced NSCLC harboring MET exon 14 mutation and treated with frontline immune checkpoint inhibitors (ICIs) are still limited. Here, we describe clinical characteristics, liver biopsy features, and management of liver injury of two patients with a diagnosis of MET exon 14-mutant NSCLC receiving capmatinib after ICI failure. On the basis of histologic findings and exclusion of other potential causes, a diagnosis of drug-induced liver injury (DILI) associated with portal fibrosis was made in both cases. The use of hepatoprotective drugs, in addition to oral ursodeoxycholic acid, resulted in liver blood tests normalization. To provide a global safety perspective, we queried the Food and Drug Administration Adverse Event Reporting System and detected a robust disproportionality signal. Out of the 918 total reports with capmatinib from the Food and Drug Administration Adverse Event Reporting System database, DILI was recorded in 43 cases (4.7%), mostly serious (93.0%) with hospitalization and death recorded in 25.6% and 16.3% of the cases, respectively. The median time to onset was 42 days, with discontinuation and positive dechallenge documented in 41.9% and 39.5% of the cases, respectively. Anti–programmed cell death protein-1 agents were coreported in 11 DILI cases. Only two cases of DILI out of 105 reports were found for tepotinib. Our data support a potential association between capmatinib and DILI in patients who have also been previously exposed to immunotherapy. Considering the potential implications for sequence strategy and timing of ICI and MET inhibitor, further investigation is warranted.

Disproportionality analyses are the most-commonly used study design used in the post-marketing phase to detect suspected adverse drug reactions in individual case safety reports. Recent years have witnessed an exponential increase in published articles on disproportionality analyses, thanks to publicly accessible databases. Unfortunately, this trend was accompanied by concerns on lack of transparency and misinterpretation of results, both generating unjustified alarm and diluting true signals into overwhelming noise. The READUS-PV guideline for reporting disproportionality analysis was developed to tackle this emerging issue. In this perspective article, we describe the rationale behind the development of the READUS-PV guideline, the first collaborative initiative to harmonize the reporting of disproportionality analyses. The adoption of the checklists will assist researchers, regulators, and reviewers in the reporting, assessment, and publication of disproportionality analyses. Acknowledging the challenges ahead of effective implementation, we advocate for a global endorsement by Pharmacology Journals. A wide dissemination of the READUS-PV guideline is crucial to foster transparency and reproducibility of pharmacovigilance research, supporting an effective exploitation of disproportionality analysis among other irreplaceable post-marketing research tools to ensure drug safety. [ABSTRACT FROM AUTHOR]

Spontaneous reporting systems remain pivotal for post-marketing surveillance and disproportionality analysis (DA) represents a recognized approach for early signal detection. Although DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient, their role remain irreplaceable for rapid detection of rare and unpredictable adverse drug reactions with strong drug-attributable component (e.g., designated medical events), especially when developed by a multidisciplinary team and combined with a careful case-by-case analysis (individual inspection of reports for causality assessment or to uncover reporting patterns and clinical features). In the recent past, a remarkable increase in publications of pharmacovigilance studies using DAs was observed, albeit the quality was debated: several publications contained "spin", namely, misinterpretation of results to infer causality, calculate incidence, or provide risk stratification, which may ultimately result in unjustified alarm. The development of dedicated Guidelines by the international READUS-PV project (https://readus-statement.org/) will allow reproducible and transparent publication of accurate DAs, thus supporting their real transferability and exploitation by regulators and clinicians. This review offered a perspective on methodological aspects (and understanding) of DAs, their rationale, design, reporting, and interpretation. [ABSTRACT FROM AUTHOR]

Introduction Antidepressant discontinuation may cause withdrawal syndrome in some cases. However, evidence on this syndrome related to individual antidepressants is limited, as well as about individual risk factors for severe reactions. Objectives To ascertain whether each individual antidepressant is associated with an increased reporting of withdrawal syndrome as compared with other medications, and to examine clinical risk factors for severe reactions. Methods We conducted a pharmacovigilance study, with a case/non-case design. We included reports of antidepressant-related withdrawal syndrome from the VigiBase, the WHO global database of individual case safety reports of suspected adverse drug reactions. We performed a disproportionality analysis (calculating reporting odds ratio (ROR) and the Bayesian information component (IC)) of reports of antidepressant-related withdrawal syndrome, comparing antidepressants to all other drugs and to buprenorphine (as a positive control). Antidepressants with significant disproportionate reporting were ranked in terms of clinical priority. We compared serious versus non-serious reactions to determine clinical risk factors for severe reactions. Results Based on 31,688 reports of antidepressant-related withdrawal syndrome, we detected a disproportionate reporting for 23 antidepressants. The ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95%CI:14.08-14.45), 17.01 for other antidepressants (95%CI:16.73-17.29), 13.65 for SSRIs (95%CI:13.41-13.90) and 2.8 for tricyclics (95%CI:2.59-3.02). Based on clinical priority ranking, the strongest signals were found for paroxetine, duloxetine, venlafaxine and desvenlafaxine (figure 1), being comparable to buprenorphine. Severe reactions were more frequently reported in males, adolescents, persons with multiple medications, and with longer treatment duration. Image: Conclusions Antidepressants are associated with increased reporting of withdrawal syndrome compared with other medications, with differences between individual antidepressants. Clinicians should be aware of such differences, when prescribing and discontinuing these drugs, as well as of the risk to experience more severe withdrawal symptoms in specific cases. Disclosure of InterestC. Gastaldon: None Declared, G. Schoretsanitis Consultant of: Dr. Schoretsanitis has served as a consultant for HLS Therapeutics, E. Arzenton : None Declared, E. Raschi : None Declared, D. Papola: None Declared, G. Ostuzzi: None Declared, U. Moretti: None Declared, E. Seifritz Grant / Research support from: Dr. Seifritz has received educational grants, consulting fees and lecture honoraria from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Ricordati, Vifor, Sunovion, Schwabe and Mepha, Consultant of: Dr. Seifritz has received educational grants, consulting fees and lecture honoraria from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Ricordati, Vifor, Sunovion, Schwabe and Mepha, J. Kane Shareolder of: LB Pharmaceuticals and Vanguard Research Group, Consultant of: Dr. Kane has been a consultant and/or advisor for or has received honoraria from Alkermes, Allergan, LB Pharmaceuticals, H. Lundbeck, Intracellular Therapies, Janssen Pharmaceuticals, Johnson and Johnson, Merck, Minerva, Neurocrine, Newron, Otsuka, Pierre Fabre, Reviva, Roche, Sumitomo Dainippon, Sunovion, Takeda, Teva and UpToDate, G. Trifirò Grant / Research support from: he was the scientific director of a Master program on pharmacovigilance, pharmacoepidemiology and real-world evidence which has received non-conditional grant from various pharmaceutical companies; he coordinated a pharmacoepidemiology team at the University of Messina until Oct 2020, which has received funding for conducting observational studies from various pharmaceutical companies (Boehringer Ingelheim, Daichii Sankyo, PTC Pharmaceuticals). He is also scientific coordinator of the academic spin-off “INSPIRE srl” which has received funding for conducting observational studies from contract research organizations (RTI Health Solutions, Pharmo Institute N.V.)., Consultant of: Dr. Trifirò has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen;, Speakers bureau of: Dr. Trifirò has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen;, C. Barbui: None Declared

Introduction Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitors (SSRIs). Objectives To ascertain whether maternal antidepressant treatment may be associated with withdrawal syndrome in neonates, investigating the comparative reporting between individual antidepressants and classes. Methods We performed a case/non-case pharmacovigilance study, searching reports of withdrawal syndrome in newborns in the VigiBase, the WHO database of suspected adverse drug reactions. Disproportionality analysis was performed, estimating reporting odds ratio (ROR) and the Bayesian information component (IC). Antidepressants were compared to all other medications, to methadone, and within each class of antidepressants (SSRIs, tricyclics (TCA) and other antidepressants). Antidepressants were ranked in terms of clinical priority, based on a semiquantitative score. Results We retrieved 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants. Compared to all other drugs, disproportionate reporting was detected for antidepressants altogether (ROR: 6.18, 95%CI:5.45-7.01), for TCAs (10.55, 95%CI:8.02-13.88), other antidepressants (ROR: 5.90, 95%CI:4.74-7.36) and SSRIs (ROR: 4.68, 95%CI:4.04-5.42). All antidepressants showed a significant disproportionality, apart from bupropion (figure 1). We did not find any disproportionate reporting for any antidepressant compared to methadone. The clinical priority ranking showed moderate clinical priority for all antidepressants, with the exception four, that had a weak one (figure 1). Most frequently reported symptoms were respiratory symptoms (n=106), irritability/agitation (n=75), tremor (n=52) and feeding problems (n=40). Image: Conclusions Exposure to antidepressants in utero is associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome for most antidepressants. Clinicians should pay extra attention to neonates with antidepressant-treated mothers. Disclosure of InterestC. Gastaldon: None Declared, E. Arzenton : None Declared, E. Raschi: None Declared, O. Spigset: None Declared, D. Papola: None Declared, G. Ostuzzi: None Declared, U. Moretti: None Declared, G. Trifirò Grant / Research support from: he was the scientific director of a Master program on pharmacovigilance, pharmacoepidemiology and real-world evidence which has received non-conditional grant from various pharmaceutical companies; he coordinated a pharmacoepidemiology team at the University of Messina until Oct 2020, which has received funding for conducting observational studies from various pharmaceutical companies (Boehringer Ingelheim, Daichii Sankyo, PTC Pharmaceuticals). He is also scientific coordinator of the academic spin-off “INSPIRE srl” which has received funding for conducting observational studies from contract research organizations (RTI Health Solutions, Pharmo Institute N.V.)., Consultant of: has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen, Speakers bureau of: has served in the last three years on advisory boards/seminars funded by SANOFI, Eli Lilly, AstraZeneca, Abbvie, Servier, Mylan, Gilead, Amgen, C. Barbui: None Declared, G. Schoretsanitis Consultant of: Dr. Schoretsanitis has served as a consultant for HLS Therapeutics and Thermo Fisher Scientific.

Cultural heritage, in the educational and training sphere, is of great impact due to its multidimensional and multidisciplinary being. Promotes a relationship of knowledge and conscious identity with the territory; it offers ways of inter- acting with cultural resources, allowing the school to guarantee pupils well-being, educational success and above all operational autonomy, through creativity and productivity. In this way, students become “producers” of content - complex and structured - and digital architectures. The digital skills of students allow them to learn, participating in society, characterized by cultural diversity, with a critical and responsible spirit, developing emotions and enhancing places and cultures. The specific tools used are all open source platforms, which allow a transfer between the virtual world and the real world, through collaboration and sharing.

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Global warming events have coincided with turnover of plant species at intervals in Earth history. As mean global temperatures rise, the number, frequency and duration of heat-waves will increase. Ginkgo biloba was grown under controlled climatic conditions at two different day/night temperature regimes (25/20 °C and 35/30 °C) to investigate the impact of heat stress. Photosynthetic CO2-uptake and electron transport were reduced at the higher temperature, while rates of respiration were greater; suggesting that the carbon balance of the leaves was adversely affected. Stomatal conductance and the potential for evaporative cooling of the leaves was reduced at the higher temperature. Furthermore, the capacity of the leaves to dissipate excess energy was also reduced at 35/30 °C, indicating that photo-protective mechanisms were no longer functioning effectively. Leaf economics were adversely affected by heat stress, exhibiting an increase in leaf mass per area and leaf construction costs. This may be consistent with the selective pressures experienced by fossil Ginkgoales during intervals of global warming such as the Triassic - Jurassic boundary or Early Eocene Climatic Optimum. The physiological and morphological responses of the G. biloba leaves were closely interrelated; these relationships may be used to infer the leaf economics and photosynthetic/stress physiology of fossil plants.