LETTER TO THE EDITOR: Many doctors take on prescribing responsibilities shortly after they graduate [1, 2], but fnal-year medical students not only feel insecure about prescribing, but also lack adequate knowledge and skills to prescribe rationally and safely [3, 4]. To address this public health concern, the European Association for Clinical Pharmacology and Therapeutics (EACPT) recommended that education in clinical pharmacology and therapeutics (CP&T) in Europe should be modernized and harmonized [5]. The frst step towards harmonization was taken in 2018 when CP&T experts reached consensus on the key learning outcomes for CP&T education in Europe [6]. The next step was to assess these outcomes in a uniform examination during undergraduate medical training [7–9]. The Prescribing Safety Assessment (United Kingdom) and the Dutch National Pharmacotherapy Assessment (The Netherlands) are currently the only national CP&T examinations [10–13]. Implementing these examinations in other European countries is difcult because of related costs and diferences in available drugs and guidelines. Therefore, in 2019, together with nine European universities, the EACPT, and the World Health Organization Europe, we started a 3-year Erasmus+-project (2019–1-NL01-KA203-060,492) to develop, test and implement an online examination on safe prescribing for medical schools in Europe: “The European Prescribing Exam” (EuroPE+, https://www.prescribingeducation.eu/). The aim of The European Prescribing Exam is to ensure that medical students in Europe graduate with prescribing competencies for safe and efective clinical practice. During the frst stage of the project, we established that EuroPE+ should focus not only on safe prescribing (e.g. contraindications, interactions) but also on broader aspects of CP&T (e.g. deprescribing, communication, personalized medicine). We identifed 43 main learning objectives and 299 attainment targets, based on previous European studies of CP&T education and the Dutch National Pharmacotherapy Assessment [6, 14, 15]. The attainment targets concern eight drug groups that junior doctors should be confdent about prescribing because these drugs are commonly prescribed or are a major cause of adverse events [16]
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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).
Rational prescribing is essential for the quality of health care. However, many final-year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely accessible in Europe. For this, we used a modified Delphi study method consisting of three parts. In part one, we created an initial list based on a literature search. In part two, a group of 64 coordinators in CPT education, selected via the Network of Teachers in Pharmacotherapy of the European Association for Clinical Pharmacology and Therapeutics, evaluated the accessibility of each medicine in his or her country, and provided a diverse group of experts willing to participate in the Delphi part. In part three, 463 experts from 24 European countries were invited to participate in a 2-round Delphi study. In total, 187 experts (40%) from 24 countries completed both rounds and evaluated 416 medicines, 98 of which were included in the final list. The top three Anatomical Therapeutic Chemical code groups were (1) cardiovascular system (n = 23), (2) anti-infective (n = 21), and (3) musculoskeletal system (n = 11). This European List of Key Medicines for Medical Education could be a starting point for country-specific lists and could be used for the training and assessment of CPT.
Door de vergrijzing neemt het aantal ouderen met complexe revalidatievragen sterk toe. Deze revalidatie vindt toenemend plaats in een ambulant traject. Therapeuten in de geriatrische revalidatiezorg geven aan dat het daardoor steeds moeilijker wordt om zicht te krijgen op de voortgang van de revalidatie. In een samenwerking tussen de Hogeschool van Amsterdam (HvA) en het Amsterdam UMC is Hipper ontwikkeld, een combinatie van een behandelprotocol en technologie om op afstand de activiteit van revalidanten thuis te meten. Via een dashboard kunnen de therapeuten de data bekijken en hun behandeling bijstellen. De B.V. Hipper Therapeutics (HipperTx) exploiteert de dienst en levert momenteel aan een aantal zorginstellingen. De zorginstellingen willen weten of ze door het inzetten van eHealth toepassingen zoals Hipper ook daadwerkelijk hun kosten kunnen verlagen in het huidige zorgstelsel. Technologieleveranciers – die Hipper en andere eHealth toepassingen willen implementeren – hebben vragen over hoe deze kunnen voldoen aan de richtlijnen voor informatiebeveiliging in de zorg: zijn de vereiste certificeringen haalbaar? In het voorliggende voorstel schetsen wij een project waarbij het Amsterdam UMC samen met de betrokken zorginstellingen een business case voor de zorg maakt en waarbij de HvA i.s.m. de technologieleveranciers de informatieprocessen in de dienst in kaart brengt voor een adequate certificering. Aan het eind van het project zal er een whitepaper geschreven zijn waarin de business case beschreven staat en zullen de voorbereidende werkzaamheden voor een NEN7150 certificering zijn uitgevoerd. Het whitepaper zal openbaar zijn en zal kunnen dienen als een voorbeeld case voor vergelijkbare implementaties. Het project draagt bij aan het Missiegedreven Innovatiebeleid, meer specifiek de missie ‘In 2030 wordt zorg 50% meer (of vaker) in de eigen leefomgeving georganiseerd, in plaats van in zorginstelling’. Daarnaast kan op basis van de uitkomsten van dit voorstel een onderzoeksaanvraag rondom doelmatigheid van ambulante revalidatie gedaan worden.
The global market for the industrial manufacturing of recombinant proteins (RPS) is steadily increasing and demand will keep rising in years to come. Currently, RPs are already an integral part of disease therapeutics, agriculture and the chemical industry and RP manufacturing methods rely heavily on host systems such as prokaryotes and, to a lesser extent, mammalian, yeast and plant cells. When comparing these host systems, all have their specific strengths and weaknesses and numerous challenges remain to improve protein manufacturing on an industrial scale. In this project, GLO Biotics proposes an innovative plant-based RP expression platform with the potential of significantly reducing costs and process requirements compared to the current state-of-the-art systems. Specifically, this novel concept is based on the use of coconut water as a natural, cell-free ‘protein production factory’. Coconut water in nuts aged 4-6 months is composed of free-floating cell nuclei devoid of cell walls, and it has been demonstrated these nuclei can express foreign proteins. Compared to existing platforms, the relative ease of delivering foreign protein-coding genes into this system, as well as the ease of recovery of the produced protein, potentially offers an innovative platform with great commercial attractiveness. In summary, the aim of this project is to provide a proof-of-concept for coconut water as a novel and competitive RP production platform by demonstrating the production and recovery of several commercially available RPs. To this end, GLO Biotics intends to collaborate with Zuyd University of Applied Sciences (Zuyd) and the Aachen Maastricht Institute for Biobased Materials (AMIBM) in demonstrating the potential of the ‘GLO-Conuts’ expression system. As a consortium, Zuyd and GLO Biotics will utilize their shared experience in molecular engineering and DNA vector technology and AMIBM will bring their expertise in plant-based RP production and recovery.
Biotherapeutic medicines such as peptides, recombinant proteins, and monoclonal antibodies have successfully entered the market for treating or providing protection against chronic and life-threatening diseases. The number of relevant commercial products is rapidly increasing. Due to degradation in the gastro-intestinal tract, protein-based drugs cannot be taken orally but need to be administered via alternative routes. The parenteral injection is still the most widely applied administration route but therapy compliance of injection-based pharmacotherapies is a concern. Long-acting injectable (LAI) sustained release dosage forms such as microparticles allow less frequent injection to maintain plasma levels within their therapeutic window. Spider Silk Protein and Poly Lactic-co-Glycolic Acid (PLGA) have been attractive candidates to fabricate devices for drug delivery applications. However, conventional microencapsulation processes to manufacture microparticles encounter drawbacks such as protein activity loss, unacceptable residual organic solvents, complex processing, and difficult scale-up. Supercritical fluids (SCF), such as supercritical carbon dioxide (scCO2), have been used to produce protein-loaded microparticles and is advantageous over conventional methods regarding adjustable fluid properties, mild operating conditions, interfacial tensionless, cheap, non-toxicity, easy downstream processing and environment-friendly. Supercritical microfluidics (SCMF) depict the idea to combine strengths of process scale reduction with unique properties of SCF. Concerning the development of long-acting microparticles for biological therapeutics, SCMF processing offers several benefits over conventionally larger-scale systems such as enhanced control on fluid flow and other critical processing parameters such as pressure and temperature, easy modulation of product properties (such as particle size, morphology, and composition), cheaper equipment build-up, and convenient parallelization for high-throughput production. The objective of this project is to develop a mild microfluidic scCO2 based process for the production of long-acting injectable protein-loaded microparticles with, for example, Spider Silk Protein or PLGA as the encapsulating materials, and to evaluate the techno-economic potential of such SCMF technology for practical & industrial production.
