Fully aware of the unusual timing of submitting a commentary 30 years later, we want to reflect on the June edition of the British Journal of Clinical Pharmacology (BJCP) (1993), which featured four research articles on education in clinical pharmacology and therapeutics (CPT) written by our former professor, Theo de Vries, and an editorial highlighting the imperative to improve CPT education, specifically by paying more attention to rational drug prescribing for common diseases.1–5 This plea was illustrated by five cartoons (Figure 1) and formed the basis for the World Health Organization's (WHO) Guide to Good Prescribing and its 6-step. The first four cartoons portrayed the suboptimal state of CPT education as a metaphorical ‘Clinical Pharmacology Continent’ (CPC) and a ‘General Practitioners Island’ (GPI), with a large gap between them. While clinical pharmacologists investigated new drug therapies, general practitioners frequently found themselves unprepared when making rational treatment decisions.1 The final cartoon introduced a solution: problembased learning education, depicted as a bridge connecting the continent and the island. Over the past 30 years, considerable progress has been achieved in bridging the gap. Therefore, we intend to illustrate this transformation with a similar cartoon (Figure 2).
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The Junior Adverse Drug Event Manager (J-ADEM) team is a multifaceted intervention focusing on real-life education for medical students that has been shown to assist healthcare professionals in managing and reporting suspected adverse drug reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb. The aim of this study was to quantify and describe the ADRs reported by the J-ADEM team and to determine the clinical potential of this approach. The J-ADEM team consisted of medical students tasked with managing and reporting ADRs in hospitalized patients. All ADRs screened and reported by J-ADEM team were recorded anonymously, and categorized and analysed descriptively. From August 2018 through January 2020, 209 patients on two wards in an academic hospital were screened for ADR events. The J-ADEM team reported 101 ADRs. Although most ADRs (67%) were first identified by healthcare professionals and then reported by the J-ADEM team, the team also reported an additional 33 not previously identified serious ADRs. In 10% of all reported ADRs, the J-ADEM team helped optimize ADR treatment. The ADR reports were largely well-documented (78%), and ADRs were classified as type A (66%), had a moderate or severe severity (85%) and were predominantly avoidable reactions (69%). This study shows that medical students are able to screen patients for ADRs, can identify previously undetected ADRs and can help optimize ADR management. They significantly increased (by 300%) the number of ADR reports submitted, showing that the J-ADEM team can make a valuable clinical contribution to hospital care.
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Abstract Specialist oncology nurses (SONs) have the potential to play a major role in monitoring and reporting adverse drug reactions (ADRs); and reduce the level of underreporting by current healthcare professionals. The aim of this study was to investigate the long term clinical and educational efects of real-life pharmacovigilance education intervention for SONs on ADR reporting. This prospective cohort study, with a 2-year follow-up, was carried out in the three postgraduate schools in the Netherlands. In one of the schools, the prescribing qualifcation course was expanded to include a lecture on pharmacovigilance, an ADR reporting assignment, and group discussion of self-reported ADRs (intervention). The clinical value of the intervention was assessed by analyzing the quantity and quality of ADR-reports sent to the Netherlands Pharmacovigilance Center Lareb, up to 2 years after the course and by evaluating the competences regarding pharmacovigilance of SONs annually. Eighty-eight SONs (78% of all SONs with a prescribing qualifcation in the Netherlands) were included. During the study, 82 ADRs were reported by the intervention group and 0 by the control group. This made the intervention group 105 times more likely to report an ADR after the course than an average nurse in the Netherlands. This is the frst study to show a signifcant and relevant increase in the number of well-documented ADR reports after a single educational intervention. The real-life pharmacovigilance educational intervention also resulted in a long-term increase in pharmacovigilance competence. We recommend implementing real-life, context- and problem-based pharmacovigilance learning assignments in all healthcare curricula.
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Inhalation therapy is essential for the management of respiratory conditions such as asthma and chronic obstructive pulmonary disease. However, current inhalation systems face limitations, including polydisperse aerosols that reduce drug delivery efficiency and complex treatment regimens that affect patient adherence. To improve drug targeting and efficacy, Gilbert Innovation B.V. is developing a next-generation soft-mist inhaler based on electrohydrodynamic atomization (EHDA), which produces uniform micrometer sized droplets. Effective drug delivery requires high flow rates and precise aerosol discharge to ensure deep lung deposition while minimizing losses to the device and oropharynx. To achieve this, the device employs a multi-nozzle system for increased flow and corona discharge needles for charge neutralization. However, ensuring uniform neutralization across multiple nozzles and maintaining stable electrospray operation remain key challenges. COSMIC aims to increase system robustness by optimizing neutralization efficiency, refining material selection, and controlling electrospray stability under varying conditions. The electrospray control system will incorporate advanced strategies leveraging computer vision, machine learning and big data analytics. These innovations will increase efficiency, accessibility and patient comfort in inhalation therapy.
Every year in the Netherlands around 10.000 people are diagnosed with non-small cell lung cancer, commonly at advanced stages. In 1 to 2% of patients, a chromosomal translocation of the ROS1 gene drives oncogenesis. Since a few years, ROS1+ cancer can be treated effectively by targeted therapy with the tyrosine kinase inhibitor (TKI) crizotinib, which binds to the ROS1 protein, impairs the kinase activity and thereby inhibits tumor growth. Despite the successful treatment with crizotinib, most patients eventually show disease progression due to development of resistance. The available TKI-drugs for ROS1+ lung cancer make it possible to sequentially change medication as the disease progresses, but this is largely a ‘trial and error’ approach. Patients and their doctors ask for better prediction which TKI will work best after resistance occurs. The ROS1 patient foundation ‘Stichting Merels Wereld’ raises awareness and brings researchers together to close the knowledge gap on ROS1-driven oncogenesis and increase the options for treatment. As ROS1+ lung cancer is rare, research into resistance mechanisms and the availability of cell line models are limited. Medical Life Sciences & Diagnostics can help to improve treatment by developing new models which mimic the situation in resistant tumor cells. In the current proposal we will develop novel TKI-resistant cell lines that allow screening for improved personalized treatment with TKIs. Knowledge of specific mutations occurring after resistance will help to predict more accurately what the next step in patient treatment could be. This project is part of a long-term collaboration between the ROS1 patient foundation ‘Stichting Merels Wereld’, the departments of Pulmonary Oncology and Pathology of the UMCG and the Institute for Life Science & Technology of the Hanzehogeschool. The company Vivomicx will join our consortium, adding expertise on drug screening in complex cell systems.
How does a specific lung cancer become resistant towards medication.The occurrence of a chromosomal translocation resulting in a ROS1 gene fusion in lung cancer is relatively rare with around 1-2% of all cases. Both Dutch (Stichting Merels Wereld) and world-wide (ROS1ders) patient advocacy groups work hard to raise awareness and bring researchers together to close the knowledge gap on ROS1 driven oncogenesis and increase the optionsfor treatment. A notorious hurdle is to achieve durable responses due to development of resistance.Ongoing mutations occurring in tumour cells lead to a heterogeneous genomic landscape and will result in outgrowth of the fastest growing tumour cell population resistant to the applied drug. The currently known resistance mechanisms can be divided in on-target (i.e. mutations in the kinasedomain of ROS1) and off-target (providing ROS1 independent growth support) mechanisms. The currently available drugs target the ROS1-fusion gene positive lung cancer cells. In addition, some of the drugs also target cancer cells with specific ROS1 resistance mutations allowing effective sequentialtreatment upon disease progression. Selection of the most optimal treatment is largely a ‘trial and error’ approach. Patients and their doctors ask for better prediction of the most effective follow-up treatment upon development of resistance. Medical Life Science & Diagnostics can help to improvetreatment by developing cell culture models which mimic the situation in resistant tumour cells.Understanding the impact of specific mutations on disease behaviour will aid in the development of patient-tailored therapeutic approaches, ultimately improving patient outcomes.
