Assessing the environmental impact of medicines in Italy using data from the Italian Medicines Agency.

Aim: This study builds on the environmental risk analysis presented in the 2022 National Report on Medicines Use in Italy by the Italian Medicines Agency and aims to assess the environmental risk posed by medicines in Italy and its regions.

Methods: The analysis selected 90 medicines based on three criteria: high utilization, low predicted no effect concentration (PNEC), and inclusion or candidacy for the European Watch List. For each medicine, the environmental risk was computed as the ratio between the predicted environmental concentration (PEC) and the PNEC.

Are Causal Statements Reported in Pharmacovigilance Disproportionality Analyses Using Individual Case Safety Reports Exaggerated in Related Citations? A Meta-epidemiological Study.

Background: Previous meta-epidemiological surveys have found considerable misinterpretation of results of disproportionality analyses. We aim to explore the relationship between the strength of causal statements used in title and abstract conclusions of pharmacovigilance disproportionality analyses and the strength of causal language used in citing studies.

Methods: On March 30, 2022, we selected the 30 disproportionality studies with the highest Altmetric Attention Scores.

Environmental sustainability-an essential component of rational use of medicines.

Human-use medicines are introduced into surface water throughout their entire life cycle, from manufacturing and consumption to improper disposal, resulting in negative effects on aquatic flora and fauna. Sustainability approaches have addressed this issue, proposing frameworks like the One Health approach. A revised definition of the rational use of medicines has also been proposed, taking into account their environmental sustainability.

The reporting of disproportionality analysis in pharmacovigilance: spotlight on the READUS-PV guideline.

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 evolving role of disproportionality analysis in pharmacovigilance.

Introduction: From 2009 to 2015, the IMI PROTECT conducted rigorous studies addressing questions about optimal implementation and significance of disproportionality analyses, leading to the development of Good Signal Detection Practices. The ensuing period witnessed the independent exploration of research paths proposed by IMI PROTECT, accumulating valuable experience and insights that have yet to be seamlessly integrated.

Areas Covered: This state-of-the-art review integrates IMI PROTECT recommendations with recent acquisitions and evolving challenges.

Emerging Toxicities of Antibody-Drug Conjugates for Breast Cancer: Clinical Prioritization of Adverse Events from the FDA Adverse Event Reporting System.

Background: Antibody-drug conjugates (ADCs) are gaining widespread use in the treatment of breast cancer, although toxicity remains an underexplored issue in the real-world clinical setting. Individual case safety reports collected in large pharmacovigilance databases can advance our knowledge on their safety profile in routine clinical practice.

Objective: We prioritized adverse events (AEs) reported with ADCs approved for breast cancer using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Enhancing Transparency in Defining Studied Drugs: The Open-Source Living DiAna Dictionary for Standardizing Drug Names in the FAERS.

Introduction: In refining drug safety signals, defining the object of study is crucial. While research has explored the effect of different event definitions, drug definition is often overlooked. The US FDA Adverse Event Reporting System (FAERS) records drug names as free text, necessitating mapping to active ingredients.

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors.

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.

Identifying Medications Underlying Communication Atypicalities in Psychotic and Affective Disorders: A Pharmacovigilance Study Within the FDA Adverse Event Reporting System.

Purpose: Communication atypicalities are considered promising markers of a broad range of clinical conditions. However, little is known about the mechanisms and confounders underlying them. Medications might have a crucial, relatively unknown role both as potential confounders and offering an insight on the mechanisms at work.

Mapping Strategies to Assess and Increase the Validity of Published Disproportionality Signals: A Meta-Research Study.

Background And Aim: Disproportionality analysis is traditionally used in spontaneous reporting systems to generate working hypotheses about potential adverse drug reactions: the so-called disproportionality signals. We aim to map the methods used by researchers to assess and increase the validity of their published disproportionality signals.

Methods: From a systematic literature search of published disproportionality analyses up until 1 January 2020, we randomly selected and analyzed 100 studies.

Cardiovascular Toxicity of Immune Checkpoint Inhibitors: A Guide for Clinicians.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment and care of patients with cancer owing to unique features, including the occurrence of the so-called immune-related adverse events (irAEs). A multidisciplinary team, possibly including a cardio-oncology specialist, is warranted to achieve a favorable patient outcome. Cardiovascular toxicity, especially myocarditis, emerged as a life-threatening irAE in the real-word setting, and the European Society of Cardiology has recently published the first guideline on cardio-oncology to increase awareness and promote a standardized approach to tackle this complex multimodal issue, including diagnostic challenges, assessment, treatment, and surveillance of patients with cancer receiving ICIs.

The environmental impact of pharmaceuticals in Italy: Integrating healthcare and eco-toxicological data to assess and potentially mitigate their diffusion to water supplies.

Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country-specific environmental risks could drive regulatory actions towards eco-friendlier drug utilization and disposal practices.

Immune Checkpoint Inhibitors and Pregnancy: Analysis of the VigiBase Spontaneous Reporting System.

In pregnancy, immune checkpoint pathways are involved in the maintenance of fetomaternal immune tolerance. Preclinical studies have shown that immune checkpoint inhibitors (ICIs) increase the risk of fetal death. Despite the fact that using ICIs in pregnant women and women of childbearing potential is not recommended, some case reports of ICI exposure in pregnancy have been published showing favorable fetal outcomes.

Exploring the underlying mechanisms of drug-induced impulse control disorders: a pharmacovigilance-pharmacodynamic study.

Introduction: Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs.

Behavioral excess and disruptive conduct: A historical and taxonomic approach to the origin of the 'impulse control disorders' diagnostic construct.

Aims: Impulse control disorders (ICDs) are iatrogenic and idiopathic conditions with psychosocial and economic consequences for the affected individuals and their families (e.g. bankruptcy and divorce).