Es el momento de revisar cómo se preparany administran los medicamentos inyectablesen los hospitales europeos / Time to review how injectable medicines are prepared and administered in European hospitals

Desde hace décadas se conoce que el uso de los medicamentos inyectables en los hospitales europeos se encuentra asociado a numerosos errores de medicación, algunos de los cuales provocan daños graves y muertes prevenibles. Se han publicado investigaciones e informes nacionales yeuropeos sobre la mejora de la seguridad del paciente que recomiendanuna mayor utilización de las unidades de preparación aséptica de los servicios de farmacia y la provisión de los medicamentos inyectables listos parasu administración, recomendaciones que apenas se han implementado.En Inglaterra, la experiencia de tratar a los pacientes con infecciónpor COVID-19 ha puesto de manifiesto otros beneficios que conlleva laampliación de las unidades de preparación aséptica de los servicios defarmacia. Estos beneficios incluyen ahorrar tiempo de enfermería, disponerde sistemas con mayor resiliencia y capacidad, reducir la variabilidad enla práctica, mejorar la satisfacción del personal clínico y del paciente, yfacilitar la administración de más medicamentos inyectables a los pacientesen sus domicilios. También se ha reconocido que se precisan actuacionesdirigidas a estandarizar las directrices y procedimientos de utilización delos medicamentos inyectables e implementar el uso de dispositivos de infusión inteligentes con software de reducción de errores de dosis, con el finde minimizar los errores en la administración de estos medicamentos. Los farmacéuticos de hospital tienen un papel clave en el desarrollo de estasactividades para que los servicios que prestan las farmacias hospitalarias europeas estén más en consonancia con los que se proporcionan en Norteamérica. (AU)

It has been known, for decades, that the use of injectable medicines inEuropean hospitals has been associated with frequent medication errors,some of which cause preventable severe harms and deaths. There havebeen national and European inquiries and reports concerning improvingpatient safety by recommending greater use of pharmacy aseptic preparation services and provision of ready-to administer injectables, which havenot been widely implemented.In England experience of treating patients with COVID-19 infectionshas brought into focus other benefits of significantly extending pharmacyaseptic preparation services. These benefits include saving nursing time,having systems in place which have resilience and capacity, reducingvariation in practice, improving clinical staff and patient experience, andenabling more injectable medicines to be administered to patients athome. It has also been recognised that more action is required to standardise policies and procedures for injectable medicines and implement theuse of smart infusion devices with dose error reduction software, to helpminimise drug administration errors.Hospital pharmacists have a key role in developing these servicesto bring European hospitals more in line with those provided by hospitalpharmacies in North America. (AU)

Time to review how injectable medicines are prepared and administered in European hospitals.

It has been known, for decades, that the use of injectable medicines in European hospitals has been associated with frequent medication errors, some of which cause preventable severe harms and deaths. There  have been national and European inquiries and reports concerning  improving patient safety by recommending greater use of pharmacy  aseptic preparation services and provision of ready-to administer  injectables, which have not been widely implemented.In England experience of treating patients with COVID-19 infections has  brought into focus other benefits of significantly extending pharmacy aseptic preparation services. These benefits include saving  nursing time, having systems in place which have resilience and capacity,  reducing variation in practice, improving clinical staff and patient  experience, and enabling more injectable medicines to be administered to  patients at home. It has also been recognised that more action is required  to standardise policies and procedures for injectable medicines and  mplement the use of smart infusion devices with dose error reduction  software, to help minimise drug administration errors.Hospital pharmacists have a key role in developing these services to bring  European hospitals more in line with those provided by hospital pharmacies in North America.

Desde hace décadas se conoce que el uso de los medicamentos  nyectables en los hospitales europeos se encuentra asociado a numerosos  errores de medicación, algunos de los cuales provocan daños graves y  muertes prevenibles. Se han publicado investigaciones e informes  nacionales y europeos sobre la mejora de la seguridad del paciente que  recomiendan una mayor utilización de las unidades de preparación  aséptica de los servicios de farmacia y la provisión de los medicamentos  inyectables listos para su administración, recomendaciones que apenas se  han implementado.En Inglaterra, la experiencia de tratar a los pacientes con infección por  COVID-19 ha puesto de manifiesto otros beneficios que conlleva la ampliación de las unidades de preparación aséptica de los servicios de farmacia. Estos beneficios incluyen ahorrar tiempo de enfermería,  disponer de sistemas con mayor resiliencia y capacidad, reducir la  variabilidad en la práctica, mejorar la satisfacción del personal clínico y del paciente, y facilitar la administración de más medicamentos inyectables a  los pacientes en sus domicilios. También se ha reconocido que se precisan  actuaciones dirigidas a estandarizar las directrices y procedimientos de  utilización de los medicamentos inyectables e implementar el uso de  dispositivos de infusión inteligentes con software de reducción de errores  de dosis, con el fin de minimizar los errores en la administración de estos  medicamentos. Los farmacéuticos de hospital tienen un papel clave en el desarrollo de  stas actividades para que los servicios que prestan las farmacias  hospitalarias europeas estén más en consonancia con los que se  proporcionan en Norteamérica.

[Injectable concentrated potassium concentrate, emblematic of the lack of safety of the drug use process in French hospitals]. / Le potassium injectable concentré, emblématique de l'insécurité médicamenteuse des hôpitaux français.

Despite its proven dangers, the ward stock drug distribution system predominates in French hospitals. This system allows 12 million injectable ampoules of concentrated potassium chloride to circulate uncontrolled each year. Such a situation is absurd for the following reasons : 1) injected by mistake, concentrated potassium kills within seconds ; 2) the true incidence of potassium-related fatalities and incidents is unknown ; 3) fatal intravenous injection of potassium produces no specific anatomical changes and subtle, if any, findings at autopsy ; 4) it is used for capital punishment by lethal injection in various countries ; and 5) healthcare worker serial killers benefit from the fact that potassium is not identifiable in post-mortem examinations and that investigations to find the murderer are complex and of uncertain outcome. Other medications classed as high-risk have similar characteristics to those of concentrated potassium solutions. Injectable potassium can therefore be regarded as emblematic of the lack of safety of the drug use process in French hospitals. The priority measure to protect patients from this deadly risk is to remove these drugs from uncontrolled ward stocks and to provide premixed potassium solutions. Evidence of the increased safety of the unit dose drug dispensing system should compel health policy makers to systematically implement it, thus bringing the drug use process into compliance with existing French and European regulations.

Le potassium injectable concentré, emblématique de l'insécurité médicamenteuse des hôpitaux français.

Despite its proven dangers, the ward stock drug distribution system predominates in French hospitals. This system allows 12 million injectable ampoules of concentrated potassium chloride to circulate uncontrolled each year. Such a situation is absurd for the following reasons : 1) injected by mistake, concentrated potassium kills within seconds ; 2) the true incidence of potassium-related fatalities and incidents is unknown ; 3) fatal intravenous injection of potassium produces no specific anatomical changes and subtle, if any, findings at autopsy ; 4) it is used for capital punishment by lethal injection in various countries ; and 5) healthcare worker serial killers benefit from the fact that potassium is not identifiable in post-mortem examinations and that investigations to find the murderer are complex and of uncertain outcome. Other medications classed as high-risk have similar characteristics to those of concentrated potassium solutions. Injectable potassium can therefore be regarded as emblematic of the lack of safety of the drug use process in French hospitals. The priority measure to protect patients from this deadly risk is to remove these drugs from uncontrolled ward stocks and to provide premixed potassium solutions. Evidence of the increased safety of the unit dose drug dispensing system should compel health policy makers to systematically implement it, thus bringing the drug use process into compliance with existing French and European regulations.

Synthesis of Mono- and Bis(fluoroalkyl)pyrimidines from FARs, Fluorinated Acetoacetates, and Malononitrile Provides Easy Access to Novel High-Value Pyrimidine Scaffolds.

A new strategy was developed using fluorinated acetoacetates, malononitrile, and fluoroalkyl amino reagents (FARs) to access unprecedented 4,6-bis(fluoroalkyl)pyrimidine-5-carboxylates, their carboxylic acid analogues, and 4-amino-6-(fluoroalkyl)pyrimidine-5-carbonitriles. An efficient cyclization step using suitable amidines was developed under microwave irradiation, providing the desired pyrimidines rapidly and efficiently. Standard saponification conditions were applied from carboxylate derivatives to access to the corresponding carboxylic acids. These new valuable building blocks, bearing either a single or two emergent fluorinated substituents, hold strong potential for medicinal and agrochemical research.

A fluorine scan of a tubulin polymerization inhibitor isocombretastatin A-4: Design, synthesis, molecular modelling, and biological evaluation.

A novel series of tubulin polymerization inhibitors, based on fluorinated derivatives of isocombretastatin A-4 was synthesized with the goal of evaluating the effect of these compounds on the proliferative activity. The introduction of fluorine atom was performed on the phenyl ring or at the linker between the two aromatic rings. The modification of isoCA-4 by introduction of difluoromethoxy group at the para-position (3i) and substitution of the two protons of the linker by two fluorine atoms (3m), produced the most active compounds in the series, with IC50 values of 0.15-2.2 nM (3i) and 0.1-2 nM (3m) respectively, against a panel of six cancer cell lines. Compounds 3i and 3m had greater antiproliferative activity in comparison with references CA-4 or isoCA-4, the presence of fluorine group leads to a significant enhancement of the antiproliferative activity. Molecular docking studies indicated that compounds 3i and 3m occupy the colchicine binding site of tubulin. Evaluation of cytotoxicity in Human noncancer cells indicated that the compounds 3i and 3m were practically ineffective in quiescent peripheral blood lymphocytes, and may have a selective antiproliferative activity against cancer cells. Analyses of cell cycle distribution, and morphological microtubules organization showed that compound 3m induced G2/M phase arrest and, dramatically disrupted the microtubule network.

Fluoroalkyl Amino Reagents for the Introduction of the Fluoro(trifluoromethoxy)methyl Group onto Arenes and Heterocycles.

Fluoroalkyl amino reagents 1a and 2a have been developed from commercially available trifluoromethyl trifluorovinyl ether via a hydroamination reaction with diethylamine or dimethylamine. These reagents can be activated by treatment with a Lewis acid and subsequently used as a mono- or dielectrophile for the introduction of the fluoro(trifluoromethoxy)methyl group, either in Vilsmeier-type acylations of aromatic substrates or in the synthesis of fluorinated pyrazoles from CH-acidic substrates and of bis-fluorinated pyrazoles, all being important building blocks for medicinal and agricultural chemistry.

Fluoroalkyl Amino Reagents (FARs): A General Approach towards the Synthesis of Heterocyclic Compounds Bearing Emergent Fluorinated Substituents.

Fluorinated heterocycles are important building blocks in pharmaceutical, agrochemical and material sciences. Therefore, organofluorine chemistry has witnessed high interest in the development of efficient methods for the introduction of emergent fluorinated substituents (EFS) onto heterocycles. In this context, fluoroalkyl amino reagents (FARs)-a class of chemicals that was slightly forgotten over the last decades-has emerged again recently and proved to be a powerful tool for the introduction of various fluorinated groups onto (hetero)aromatic derivatives.

A Major Advance in the Synthesis of Fluoroalkyl Pyrazoles: Tuneable Regioselectivity and Broad Substitution Patterns.

A novel approach towards highly functionalized fluoroalkyl pyrazoles was developed by using fluoroalkyl amino reagents in combination with a variety of fluorinated ketimines. Tuneable introduction of fluoroalkyl groups in the 3- and 5-positions was possible by using vinamidinium intermediates or the corresponding enamino ketones after hydrolysis. These high-value building blocks can give rise to a large number of analogues for bioactivity screening and discovering new heterocyclic bioactive ingredients in various life science fields.

In Situ Generated Fluorinated Iminium Salts for Difluoromethylation and Difluoroacetylation.

The use of TFEDMA, a fluoroalkyl amino reagent, for the difluoromethylation and difluoroacylation of arenes, heteroarenes, and C-H acidic compounds is reported. This approach allows for an efficient access to difluoromethylated products of high added value in good to excellent yields and with scale-up possibilities.

[mediEVAL: a new evaluating tool for the medication-use system]. / mediEVAL : un nouvel outil d'évaluation de la prise en charge médicamenteuse.

PURPOSES: A new methodology to evaluate the medication-use system based on a risk cartography tool, has been developed. This work has been promoted by the Observatoire du médicament et des dispositifs médicaux stériles et de l'innovation thérapeutique (OMEDIT) from Provence-Alpes-Côte d'Azur (PACA)-Corse regions. METHODS: This new methodology has been developed with Excel (Microsoft(®)) and has led to the mediEVAL tool. It consists in two categories of Excel files: evaluating Excel files (1 for each job of the medication-use system) and synthesis Excel files which allow to compile a group of evaluating files for a defined area (department, hospital…). RESULTS AND CONCLUSION: mediEVAL is a new tool to evaluate quality and risk management of the entire medication-use system which has to be used by private or public hospitals of PACA and Corsica areas in their appropriate medication-use contract. Then, the OMEDIT can get data to provide an inventory of fixtures of the PACA-Corse area medication-use system situation.