Unveiling the Burden of Drug-Induced Impulsivity: A Network Analysis of the FDA Adverse Event Reporting System.

INTRODUCTION: Impulsivity induced by dopaminergic agents, like pramipexole and aripiprazole, can lead to behavioral addictions that impact on social functioning and quality of life of patients and families (e.g., resulting in unemployment, marital problems, anxiety). These secondary effects, interconnected in networks of signs and symptoms, are usually overlooked by clinical trials, not reported in package inserts, and neglected in clinical practice. OBJECTIVE: This study explores the syndromic burden of impulsivity induced by pramipexole and aripiprazole, pinpointing key symptoms for targeted mitigation. METHODS: An event-event Information Component (IC) on the FDA Adverse Event Reporting System (FAERS) (January 2004 to March 2022) identified the syndrome of events disproportionally co-reported with impulsivity, separately for pramipexole and aripiprazole. A greedy-modularity clustering on composite network analyses (positive pointwise mutual information [PPMI], Ising, Φ) identified sub-syndromes. Bayesian network modeling highlighted possible precipitating events. RESULTS: Suspected drug-induced impulsivity was documented in 7.49% pramipexole and 4.50% aripiprazole recipients. The highest IC concerned obsessive-compulsive disorder (reporting rate = 26.77%; IC median = 3.47, 95% confidence interval [CI] = 3.33-3.57) and emotional distress (21.35%; 3.42, 3.26-3.54) for pramipexole, bankruptcy (10.58%; 4.43, 4.26-4.55) and divorce (7.59%; 4.38, 4.19-4.53) for aripiprazole. The network analysis identified delusional jealousy and dopamine dysregulation sub-syndromes for pramipexole, obesity-hypoventilation and social issues for aripiprazole. The Bayesian network highlighted anxiety and economic problems as potentially precipitating events. CONCLUSION: The under-explored consequences of drug-induced impulsivity significantly burden patients and families. Network analyses, exploring syndromic reactions and potential precipitating events, complement traditional techniques and clinical judgment. Characterizing the secondary impact of reactions will support informed patient-centered decision making.

Adopting STOPP/START Criteria Version 3 in Clinical Practice: A Q&A Guide for Healthcare Professionals.

The growing complexity of geriatric pharmacotherapy necessitates effective tools for mitigating the risks associated with polypharmacy. The Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP)/Screening Tool to Alert doctors to Right Treatment (START) criteria have been instrumental in optimizing medication management among older adults. Despite their large adoption for improving the reduction of potentially inappropriate medications (PIM) and patient outcomes, the implementation of STOPP/START criteria faces notable challenges. The extensive number of criteria in the latest version and time constraints in primary care pose practical difficulties, particularly in settings with a high number of older patients. This paper critically evaluates the challenges and evolving implications of applying the third version of the STOPP/START criteria across various clinical settings, focusing on the European healthcare context. Utilizing a "Questions & Answers" format, it examines the criteria's implementation and discusses relevant suitability and potential adaptations to address the diverse needs of different clinical environments. By emphasizing these aspects, this paper aims to contribute to the ongoing discourse on enhancing medication safety and efficacy in the geriatric population, and to promote more person-centred care in an aging society.

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). METHODS: We assessed clinical priority of AEs reported in FAERS (February 2013-March 2022) for trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG) by attributing a score to each AE disproportionally reported with ADCs. Four criteria were assessed: clinical relevance, reporting rate, reported case fatality rate, and stability of disproportionality signals (consistency of the reporting odds ratio across multiple analyses using three different comparators). RESULTS: We retained 6589 reports (77.4% referring to T-DM1 as suspect), and 572 AEs generated a disproportionality signal in at least one analysis. The majority of these AEs (62%) were classified as moderate clinical priorities (e.g., interstitial lung disease with T-DXd, thrombocytopenia, peripheral neuropathy with T-DM1, febrile neutropenia, and large intestine perforation with SG). Three AEs emerged as high clinical priorities (6 points): septic shock and neutropenic colitis with SG (N = 8 and 13, with median onset 13 and 10 days, respectively), without co-reported immunosuppressive agents; and pulmonary embolism with T-DM1 (N = 31, median onset 109 days, 52% with reported metastasis). CONCLUSION: The heterogeneous spectrum of post-marketing toxicities for ADCs used in breast cancer, as emerging from the FAERS, is largely in line with preapproval evidence. Although causality cannot be proved, we call for increased awareness by oncologists on potential serious unexpected reactions, including early onset of septic shock and neutropenic colitis with SG, and late emergence of pulmonary embolism with T-DM1.

Learning of clinical pharmacology by future prescribers in Bologna: Teachers' and students' reflections on the way forward.

AIMS: In this reflection paper, the authors, based on their experience as teachers and students of the courses of Pharmacology at the University of Bologna, reflect on their specific roles towards innovation in the teaching of Clinical Pharmacology. METHODS: Strengths, weaknesses and challenges are presented as identified during the teaching and learning experience in the currently evolving medical degree programmes of the University in light of current trends in medical education. RESULTS: Keeping in mind the identified challenges together with the features proposed for the model prescriber (knowledgeable, contemporary, communicative and safe), we indicate some ways to improve the students' experience and make sure they develop up-to-date skills in Clinical Pharmacology taking advantage of recent ongoing collaborations at European level. International collaboration is indeed necessary to adequately address the current challenges of teaching clinical pharmacology. CONCLUSION: Our shared conclusion is that empowering students with a scientifically sound method to retrieve relevant information and developing their skills to communicate in an interprofessional and, wherever possible, international environment is the key to prepare future prescribers and, ultimately, to improve patient safety.

Continuing medical education during pandemic waves of COVID-19: Consensus from medical faculties in Asia, Australia and Europe.

This article was migrated. The article was marked as recommended. Medical faculties have the responsibility to train tomorrow's doctors and in a crisis face the challenge of delivering students into the workforce promptly and safely. Worldwide, medical faculties have faced unprecedented disruptions from viral outbreaks and pandemics including SARS, Ebola, H1N1 and COVID-19 which bring unique challenges. Currently there is worldwide disruption to medical faculties and medical education due to COVID-19. Despite close links with clinical medicine and the known risks of pandemics, many medical faculties have been caught off guard without pandemic planning in place, to deal with an exponential rise in infections and deaths, overwhelmed health services and widespread community risk of transmission. Assessing transmission risk of COVID-19 in teaching, clinical and community attachments and continuing medical education is paramount as medical faculties face subsequent pandemics waves. Consensus statements based on best available evidence and international expertise from medical faculties in Asia, Australia and Europe were developed to help guide the protection of staff and students, priorities on teaching activities and further educational development. Infection prevention, infection control, contact tracing and medical surveillance are detailed to minimise transmission and to enhance safety. Recommendations on teaching activities planning can enhance responsiveness of medical faculties to tackle subsequent waves of COVID-19 infection. A global approach and dialogue are encouraged.