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The pandemic subsequent to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus resulted, for the French institutional pharmacovigilance, in a "health crisis" in 2 phases: the coronavirus disease 2019 - "COVID-19" phase during which the missions of the Regional Pharmacovigilance Centres (RPVC) were to detect a possible impact of drugs on this disease, as whether existed a possible aggravating role of certain drugs, or the safety profile of drugs used for the management of COVID-19 could evolve. The second phase followed the availability of COVID-19 vaccines, during which the RPVCs' missions were to detect as early as possible any new serious adverse effect, source of a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two periods, signal detection remained the core business of the RPVCs. The RPVCs had to organize themselves to handle an historical surge of declarations and requests for advice, whereas the RPVCs in charge of monitoring vaccines had to deal with an extraordinary dense activity over a long period of time, in order to produce in real time and on a weekly basis, a summary of all the declarations and an analysis of safety signals. The national organization put in place made it possible to meet the challenge of real-time pharmacovigilance monitoring of 4 vaccines with conditional marketing authorizations. Short-circuit efficient exchanges with the French Regional Pharmacovigilance Centres Network was paramount for the French National Agency for medicines and health products (Agence nationale de sécurité du médicament et des produits de santé) to develop an optimal collaborative partnership. The RPVC network has shown agility and flexibility, has been able to adapt swiftly and demonstrated its effectiveness in the early detection of safety signals. This crisis confirmed the superiority of manual/human signal detection as the most effective and powerful tool to date, to rapidly detect a new adverse drug reaction and enable to elaborate rapid measures of risk reduction. In order to maintain the performance of French RPVCs in signal detection and to monitor all drugs as they should and as expected by our fellow citizens, a new funding model correcting the inadequacy of RPVCs' expertise resources in relation to the volume of reports should be considered.
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OBJECTIVES: Diabetes is a major public health problem in Canada and requires multifactorial, consistent clinical management. The COVID-19 pandemic has increased challenges in the management of many chronic ailments, including diabetes. Diabetes was associated with a higher risk of severe illness in the context of COVID-19. Pandemic restrictions also impacted diabetes care continuity, which may have contributed to an increased risk of diabetes-related complications and mortality. METHODS: This was a retrospective cross-sectional study of prescription patterns of antihyperglycemic medications claimed by individuals with type 2 diabetes (T2D) before and during the COVID-19 pandemic using the IQVIA Canada Longitudinal Prescription Claims database. The study period was from March 1, 2018, to February 28, 2021. The study outcomes are described on a monthly, quarterly, and yearly basis and overall, and by medication, medication class, and insurance coverage type. "New-to-molecule" patients were defined as those claiming a medication during the analysis period that they had no history of claiming in the database. Adults with at least 1 year of prescription history available and claiming their first prescription for an antihyperglycemic drug during the analysis period were classified as newly diagnosed with T2D. RESULTS: A similar number of people had at least 1 non-insulin antihyperglycemic prescription during the baseline, prepandemic, and pandemic periods in Canada (1,778,155, 1,822,403, and 1,797,272, respectively). However, the number of people initiating newer antihyperglycemic medications decreased at the beginning of the pandemic, in contrast to older medications, which remained consistent across the pandemic period. The number of people diagnosed with T2D decreased in the early months of the pandemic but recovered by October 2020. CONCLUSION: The COVID-19 epidemic in Canada impacted clinical care for at-risk Canadians, with fewer being prescribed newer antihyperglycemic drugs and a reduction in the number of diagnoses of T2D.
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The sacrosanct image that the prescriber and the public had of the Marketing Authorization (AMM) three or four decades ago has changed significantly in recent years, following the consideration – sometimes controversial – some of its shortcomings or weaknesses. The text of this article discusses some of the factors that may explain this change in mentality, which is harmful to patient safety. Among these factors, mention should be made of the quite understandable lag of certain MAs on the data acquired from science, a sometimes excessive and counterproductive formalism or even possible disagreements between the Agencies responsible for the registration of medicinal products. But it is especially necessary to retain certain fragile marketing authorizations, with a degraded image, prematurely granted on non-optimal levels of evidence with the aim of accelerating patients' access to new so-called "promising” drugs. Finally, the intervention of patients, now very important in the field, is a social phenomenon that should not be overlooked, either because they are wary of the drug and its evaluation or because they put pressure on the prescriber to obtain a prescription. off-label touted in social networks. The fact remains that MA remains the reference and benchmark to be respected for optimal, secure and responsible drug prescription. A positive point is that the pandemic due to COVID-19 will have enabled journalists to better master the notions of level of proof and balance between benefits and risks. At the same time, it will have enabled the public, for the most part, to understand what an MA is and to admit the need for it, despite the erosion of its confidence in scientific expertise and its suspicion towards to health institutions. If there is no reason to regret that more transparency and health democracy allow the citizen to appropriate the meaning and the determinants of MAID, there is reason, for evaluation specialists, to call for the maintenance of its rigor in the very interest of patients and for the health authorities to maintain it. © 2022 l'Académie nationale de médecine;L'image sacro-sainte que le prescripteur et le public se faisaient de l'Autorisation de mise sur le marché (AMM) il y a trois ou quatre décennies a notablement évolué depuis quelques années, suite à la prise en compte – parfois polémique – de certaines de ses insuffisances ou de ses faiblesses. Le texte de cet article évoque quelques-uns des facteurs pouvant expliquer cette évolution des mentalités, délétère pour la sécurité des patients. Parmi ces facteurs, on mentionnera le retard bien compréhensible de certaines AMM sur les données acquises de la science, un formalisme parfois excessif et contre-productif ou encore de possibles discordances d'avis entre Agences responsables de l'enregistrement des médicaments. Mais il faut surtout retenir certaines AMM fragiles, d'image dégradée, prématurément octroyées sur des niveaux de preuve non optimaux dans le but d'accélérer l'accès des malades aux nouveaux médicaments dits « prometteurs ». Enfin, l'intervention des patients, désormais très importante dans le domaine, est un phénomène de société à ne pas méconnaître, soit qu'ils se méfient du médicament et de son évaluation ou qu'ils fassent pression sur le prescripteur pour obtenir une prescription hors AMM vantée dans les réseaux sociaux. Il n'en demeure pas moins que l'AMM reste la référence et le repère à respecter pour une prescription médicamenteuse optimale, sécurisée et responsable. Un point positif est que la pandémie due au COVID-19 aura permis aux journalistes de mieux maîtriser les notions de niveau de preuve et de balance bénéfices/risques. Par la même occasion, elle aura permis au public, dans sa très grande majorité, de comprendre ce qu'est une AMM et d'en admettre la nécessité, malgré l'érosion de sa confiance dans l'expertise scientifique et sa suspicion vis-à-vis des institutions de santé. S'il n'y a pas lieu de regretter que davantage de trans arence et de démocratie sanitaire permettent au citoyen de s'approprier la signification et les déterminants de l'AMM, il y a lieu, pour les spécialistes de l'évaluation, d'appeler au maintien de sa rigueur dans l'intérêt même des patients et pour les autorités de santé de la maintenir. © 2022 l'Académie nationale de médecine
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INTRODUCTION: The use of electronic systems in prescription is considered as the final solution to overcome the many problems of the paper transcription process, especially with the outbreak of Coronavirus needs more attention than before. But despite the many advantages, its implementation faces many challenges and obstacles. Therefore, the present study was conducted to review the effectiveness of computerized physician order entry systems (CPOE) on relative risk reduction on medication error and adverse drug events (ADE). METHOD: This study is one of the systematic review studies that was conducted in 2021. In this study, searching for keywords such as E-Electronic Prescription, Patient safety, Medication Errors prescription, Drug Interactions, orginal articles from 2000 to October-2020 in the valid databases such as ISI web of Science PubMed Embase, Scopus and search engines like google was done. The included studies were based on the main objectives of the study and based on the inclusion criteria after several stages of review and quality evaluation. In fact, the main criteria for selecting articles were studies that compared the rate of medication errors with or without assessing the associated harms (real or potential) before and after the implementation of EMS. RESULTS: Out of 110 selected studies after initial screening, only 16 articles were selected due to their relevance. Among the final studies, there was a significant heterogeneity. Only 6 studies were of good quality. Of the 10 studies prescribing error rates, 9 reported reductions, but variable denominators prevented meta-analysis. Twelve studies provided specific examples of systemic drug errors. 5 cases reported their occurrence slightly. Out of 9 cases that analyzed the effects on drug error rate, 7 cases showed a significant relative reduction between 13 and 99%. Four of the six studies that analyzed the effects on potential ADEs showed a significant relative reduction of between 35 and 98%. Two of the four studies that analyzed the effect of ADEs showed a relative reduction of between 30 and 84%. CONCLUSION: Finally, e-prescribing seems to reduce the risk of medication errors and ADE. However, the studies differed significantly in terms of setting, design, quality and results. More randomized controlled trials (RCTs) are needed to further improve the evidence of health informatics information.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Electronic Prescribing , Medical Order Entry Systems , Humans , Medication Errors/prevention & control , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Patient SafetyABSTRACT
PURPOSE: To evaluate changes in the medication adherence of glaucoma patients during the COVID-19 pandemic and the factors influencing medication adherence. MATERIALS AND METHODS: This cross-sectional study included a total of 197 glaucoma patients who were followed for at least six months in the Glaucoma Unit of the Ophthalmology Department of Inonu University, Faculty of Medicine. Patients were given a 28-item questionnaire, including the eight-item Morisky Medication Adherence Questionnaire, to evaluate medication adherence. Demographic and clinical data were recorded. P<0.05 was considered statistically significant. RESULTS: Interruption of glaucoma clinic visits during the pandemic was reported by 82 (41.6%) patients. Nonadherence was reported by 56 patients (28.4%) (95% confidence interval: 22.1-34.7). For these patients, the most common reasons for nonadherence were forgetfulness (50%), the inability to receive a prescription for the drug (10.7%) and being busy (10.7%). Factors influencing nonadherence were determined to be younger age, female gender, interruption of glaucoma clinic visits and high-income levels (PË0.05). CONCLUSION: Interruption of glaucoma clinic visits during the COVID-19 pandemic and the resulting inability to have medications prescribed resulted in patient nonadherence with medication use.
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The Covid-19 pandemic has shown France's exposure to drug supply difficulties and has thus highlighted the public health challenge represented by tensions and disruptions in the supply of drugs in an epidemic situation. France's exposure to drug unavailability has been the subject of several reports and legislative and regulatory provisions. If the law of January 26, 2016 on the modernization of our health system introduced provisions in response to the rapid increase in the frequency of shortages in the supply of health products, the law on the financing of social security for 2020 reinforced the system tackling drug shortages by introducing an obligation for marketing authorization holders to hold up to four months' stock for all drugs. The implementing decree of March 30, 2021, relating to the savety stock intended for the national market differentiated the quantities of stock according to the medicines for a period of one week to two months to cover needs. This last duration can be reduced or increased "without exceeding four months”. These quantities below what the law authorizes are analyzed regarding the principle of free movement of goods provided for by the Treaty on the Functioning of the European Union and the case law of the Court of Justice of the European Union. © 2022 l'Académie nationale de médecine La pandémie à la Covid-19 a montré l'exposition de la France à des difficultés d'approvisionnement en médicaments et a ainsi mis en lumière l'enjeu de santé publique que représentent les tensions et ruptures d'approvisionnement de médicaments en situation épidémique. L'exposition de la France à l'indisponibilité de médicaments a fait l'objet de plusieurs rapports et de dispositions législatives et règlementaires. Si la loi du 26 janvier 2016 de modernisation de notre système de santé a introduit des dispositions devant l'accroissement rapide de la fréquence des ruptures d'approvisionnement en produits de santé, la loi de financement de la sécurité sociale pour 2020 a renforcé le dispositif de lutte contre les pénuries de médicaments en instaurant une obligation pour les titulaires d'autorisation de mise sur le marché de constituer jusqu'à quatre mois de stock pour tous les médicaments. Le décret d'application du 30 mars 2021 relatif au stock de sécurité destiné au marché national a différencié les quantités de stock selon les médicaments pour une durée d'une semaine à deux mois de couverture des besoins. Cette dernière durée pouvant être diminuée ou augmentée « sans excéder quatre mois ». Ces quantités en deçà de ce que la loi autorise sont analysées au regard du principe de libre circulation des marchandises prévue par le Traité sur le fonctionnement de l'Union européenne et de la jurisprudence de la Cour de justice de l'Union européenne. © 2022 l'Académie nationale de médecine
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Résumé L'image sacro-sainte que le prescripteur et le public se faisaient de l'Autorisation de mise sur le marché (AMM) il y a trois ou quatre décennies a notablement évolué depuis quelques années, suite à la prise en compte – parfois polémique – de certaines de ses insuffisances ou de ses faiblesses. Le texte de cet article évoque quelques-uns des facteurs pouvant expliquer cette évolution des mentalités, délétère pour la sécurité des patients. Parmi ces facteurs, on mentionnera le retard bien compréhensible de certaines AMM sur les données acquises de la science, un formalisme parfois excessif et contre-productif ou encore de possibles discordances d'avis entre Agences responsables de l'enregistrement des médicaments. Mais il faut surtout retenir certaines AMM fragiles, d'image dégradée, prématurément octroyées sur des niveaux de preuve non optimaux dans le but d'accélérer l'accès des malades aux nouveaux médicaments dits « prometteurs ». Enfin, l'intervention des patients, désormais très importante dans le domaine, est un phénomène de société à ne pas méconnaître, soit qu'ils se méfient du médicament et de son évaluation ou qu'ils fassent pression sur le prescripteur pour obtenir une prescription hors AMM vantée dans les réseaux sociaux. Il n'en demeure pas moins que l'AMM reste la référence et le repère à respecter pour une prescription médicamenteuse optimale, sécurisée et responsable. Un point positif est que la pandémie due au COVID-19 aura permis aux journalistes de mieux maîtriser les notions de niveau de preuve et de balance bénéfices/risques. Par la même occasion, elle aura permis au public, dans sa très grande majorité, de comprendre ce qu'est une AMM et d'en admettre la nécessité, malgré l'érosion de sa confiance dans l'expertise scientifique et sa suspicion vis-à-vis des institutions de santé. S'il n'y a pas lieu de regretter que davantage de transparence et de démocratie sanitaire permettent au citoyen de s'approprier la signification et les déterminants de l'AMM, il y a lieu, pour les spécialistes de l'évaluation, d'appeler au maintien de sa rigueur dans l'intérêt même des patients et pour les autorités de santé de la maintenir. Summary The sacrosanct image that prescribers and the public had of Drug Marketing Authorization (AMM) three or four decades ago has changed significantly over the past few years, following the recognition, – sometimes controversial – of some of its shortcomings or weaknesses. The text of this article discusses some of the factors that may explain this change in mentality, which is harmful to patient safety. Among these factors, we can mention the understandable delay of some AMMs on the data acquired from science, a sometimes excessive and counterproductive formalism, or even possible disagreements between the Agencies responsible for the registration of medicinal products. But above all, it is necessary to retain that some AMMs are fragile, with a degraded image, prematurely granted on sub-optimal levels of evidence with the aim of accelerating patients' access to new, so-called "promising” drugs. Finally, the intervention of patients, now very important in this field, is a social phenomenon that should not be overlooked, either because they are wary of the drug and its evaluation or because they put pressure on the prescriber to obtain an off-label prescription touted in social networks. The fact remains that the AMM remains the reference and the benchmark to be respected for an optimal, secure and responsible drug prescription. A positive point is that the pandemic due to COVID-19 has enabled journalists to better master the notions of level of proof and benefit/risk balance. At the same time, it will have enabled the vast majority of the public to understand what AMM is and to accept, for the most part, the need for it, despite the erosion of their confidence in scientific expertise and their suspicion towards the health institutions. If there is no reason to regret that more transparenc and health democracy allow the citizen to appropriate the meaning and the determinants of AMM, there is reason, for the evaluation specialists to call for maintaining its rigor in the very interest of patients and for health authorities to maintain it.
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Résumé La pandémie à la Covid-19 a montré l'exposition de la France à des difficultés d'approvisionnement en médicaments et a ainsi mis en lumière l'enjeu de santé publique que représentent les tensions et ruptures d'approvisionnement de médicaments en situation épidémique. L'exposition de la France à l'indisponibilité de médicaments a fait l'objet de plusieurs rapports et de dispositions législatives et règlementaires. Si la loi du 26 janvier 2016 de modernisation de notre système de santé a introduit des dispositions devant l'accroissement rapide de la fréquence des ruptures d'approvisionnement en produits de santé, la loi de financement de la sécurité sociale pour 2020 a renforcé le dispositif de lutte contre les pénuries de médicaments en instaurant une obligation pour les titulaires d'autorisation de mise sur le marché de constituer jusqu'à quatre mois de stock pour tous les médicaments. Le décret d'application du 30 mars 2021 relatif au stock de sécurité destiné au marché national a différencié les quantités de stock selon les médicaments pour une durée d'une semaine à deux mois de couverture des besoins. Cette dernière durée pouvant être diminuée ou augmentée « sans excéder quatre mois ». Ces quantités en deçà de ce que la loi autorise sont analysées au regard du principe de libre circulation des marchandises prévue par le Traité sur le fonctionnement de l'Union européenne et de la jurisprudence de la Cour de justice de l'Union européenne. Summary The Covid-19 pandemic has shown France's exposure to drug supply difficulties and has thus highlighted the public health challenge represented by tensions and disruptions in the supply of drugs in an epidemic situation. France's exposure to drug unavailability has been the subject of several reports and legislative and regulatory provisions. If the law of January 26, 2016 on the modernization of our health system introduced provisions in response to the rapid increase in the frequency of shortages in the supply of health products, the law on the financing of social security for 2020 reinforced the system tackling drug shortages by introducing an obligation for marketing authorization holders to hold up to four months' stock for all drugs. The implementing decree of March 30, 2021, relating to the savety stock intended for the national market differentiated the quantities of stock according to the medicines for a period of one week to two months to cover needs. This last duration can be reduced or increased "without exceeding four months”. These quantities below what the law authorizes are analyzed regarding the principle of free movement of goods provided for by the Treaty on the Functioning of the European Union and the case law of the Court of Justice of the European Union.
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Since December 2019, the world is confronted with the outbreak of the respiratory disease COVID-19. At the beginning of 2020, the COVID-19 epidemic evolved into a pandemic, which continues to this day. Within many countries, several control strategies or combinations of them, like restrictions (e.g. lockdown actions), medical care (e.g. development of vaccine or medicaments) and medical prevention (e.g. hygiene concept), were established with the goal to control the pandemic. Depending on the chosen control strategy, the COVID-19 spreading behavior slowed down or approximately stopped for a defined time range. This phenomenon is called saturation effect and can be described by saturation models: E.g. a fundamental approach is Verhulst (1838). The model parameter allows the interpretation of the spreading speed (growth) and the saturation effect in a sound way. This paper shows results of a research study of the COVID-19 spreading behavior and saturation effects depending on different pandemic control strategies in different countries and time phases based on Johns Hopkins University data base (2020). The study contains the analyzing of saturation effects related to short time periods, e.g. possible caused by lockdown strategies, geographical influences and medical prevention activities. The research study is focusing on reference countries like Germany, Japan, Denmark, Iceland, Ireland and Israel. © ESREL 2021. Published by Research Publishing, Singapore.
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OBJECTIVES: The aim of the study is to provide an overview of Drug-drug Interactions (DDIs) and adverse effects caused by drugs used in SARS-CoV-2 infection during the first epidemic wave. METHODS: We retrospectively analyzed patients treated by drugs used in SARS-CoV-2 infection (Azithromycin, Hydroxychloroquine and/or Lopinavir/ritonavir) between 15th March 2020 to 17th April 2020. A review of adverse events and DDI-risky drug association on medical record was conducted for each patient. Each adverse events was analyzed by the Centre régional de pharmacovigilance (CRPV) to assess causality of drugs used in SARS-CoV-2 infection. RESULTS: A total of 312 precriptions were analyzed during the period, of which 110 prescriptions had 157 drug association at risk of DDIs; 26 adverse events were reported. Causality assessment by CRPV concluded that 10 (35,7 %) adverse effects were possibly related to SARS-CoV-2 drugs with only 2 (7,1 %) related to DDIs. CONCLUSIONS: Despite risk of adverse drug reactions and DDIs related to drugs used in SARS-CoV-2 infection, few iatrogenics diseases were found.
Subject(s)
COVID-19 Drug Treatment , Antiviral Agents/adverse effects , Drug Interactions , Humans , Hydroxychloroquine/adverse effects , Retrospective Studies , Ritonavir/adverse effects , SARS-CoV-2ABSTRACT
This COVID-19 pandemic is impacting the world in health and economic terms since 2020 with more than 200 million confirmed infected people and more than 4 million deaths across 190 countries. Treatment used against COVID-19 disease has initially been based on the combination of several medicaments, such as hydroxychloroquine/chloroquine, azithromycin and kaletra, each of which can individually delay the ventricular depolarization and repolarization processes through morphological changes in the patient's electrocardiogram. These changes can produce serious arrhythmias that lead to the sudden death of the patient.This paper presents an interpretable fuzzy rule-based system for fatal ventricular arrhythmia risk level estimation due to COVID-19 treatment, whose decisions are made on the basis of the evolution of electrocardiogram morphology and certain patient's clinical information. For the risk level estimation, the proposed fuzzy rule-based system considers three different risk levels (High, Moderate and Low) which are indicated by means of three different colors (Red, Orange and Green). Decisions made by the fuzzy rule-based system present a reliable behavior in comparison with cardiologist's decision. To be precise, the obtained accuracy, when comparing both decisions, reaches the 96.43%, which, joint to the high measured interpretability of the decision making system, result in a powerful tool in order to avoid death in patients, even in health centers without specialized clinical staff, and to reduce the stress in medical centers by reducing reaction times in critical patient situations. © 2021 IEEE.
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Targeted protein degradation (TPD), discovered twenty years ago through the PROTAC technology, is rapidly developing thanks to the implication of many scientists from industry and academia. PROTAC chimeras are heterobifunctional molecules able to link simultaneously a protein to be degraded and an E3 ubiquitin ligase. This allows the protein ubiquitination and its degradation by 26S proteasome. PROTACs have evolved from small peptide molecules to small non-peptide and orally available molecules. It was shown that PROTACs are capable to degrade proteins considered as "undruggable" i.e. devoid of well-defined pockets and deep grooves possibly occupied by small molecules. Among these "hard to drug" proteins, several can be degraded by PROTACs: scaffold proteins, BAF complex, transcription factors, Ras family proteins. Two PROTACs are clinically tested for breast (ARV471) and prostate (ARV110) cancers. The protein degradation by proteasome is also induced by other types of molecules: molecular glues, hydrophobic tagging (HyT), HaloPROTACs and homo-PROTACs. Other cellular constituents are eligible to induced degradation: RNA-PROTACs for RNA binding proteins and RIBOTACs for degradation of RNA itself (SARS-CoV-2 RNA). TPD has recently moved beyond the proteasome with LYTACs (lysosome targeting chimeras) and MADTACs (macroautophagy degradation targeting chimeras). Several techniques such as screening platforms together with mathematical modeling and computational design are now used to improve the discovery of new efficient PROTACs.
TITLE: Dégradation induite des protéines par des molécules PROTAC et stratégies apparentées : développements à visée thérapeutique. ABSTRACT: Alors que, pour la plupart, les médicaments actuels sont de petites molécules inhibant l'action d'une protéine en bloquant un site d'interaction, la dégradation ciblée des protéines, découverte il y a une vingtaine d'années via les petites molécules PROTAC, connaît aujourd'hui un très grand développement, aussi bien au niveau universitaire qu'industriel. Cette dégradation ciblée permet de contrôler la concentration intracellulaire d'une protéine spécifique comme peuvent le faire les techniques basées sur les acides nucléiques (oligonucléotides antisens, ARNsi, CRISPR-Cas9). Les molécules PROTAC sont des chimères hétéro-bifonctionnelles capables de lier simultanément une protéine spécifique devant être dégradée et une E3 ubiquitine ligase. Les PROTAC sont donc capables de provoquer l'ubiquitinylation de la protéine ciblée et sa dégradation par le protéasome 26S. De nature peptidique, puis non peptidique, les PROTAC sont maintenant administrables par voie orale. Ce détournement du système ubiquitine protéasome permet aux molécules PROTAC d'élargir considérablement le champ des applications thérapeutiques puisque l'élimination de protéines dépourvues de poches ou de crevasses bien définies, dites difficiles à cibler, devient possible. Cette technologie versatile a conduit à la dégradation d'une grande variété de protéines comme des facteurs de transcription, des sérine/thréonine/tyrosine kinases, des protéines de structure, des protéines cytosoliques, des lecteurs épigénétiques. Certaines ligases telles que VHL, MDM2, cereblon et IAP sont couramment utilisées pour être recrutées par les PROTAC. Actuellement, le nombre de ligases pouvant être utilisées ainsi que la nature des protéines dégradées sont en constante augmentation. Deux PROTAC sont en étude clinique pour les cancers du sein (ARV471) et de la prostate (ARV110). La dégradation spécifique d'une protéine par le protéasome peut aussi être induite par d'autres types de molécules synthétiques : colles moléculaires, marqueurs hydrophobes, HaloPROTAC, homo-PROTAC. D'autres constituants cellulaires sont aussi éligibles à une dégradation induite : ARN-PROTAC pour les protéines se liant à l'ARN et RIBOTAC pour la dégradation de l'ARN lui-même comme celui du SARS-CoV-2. Des dégradations induites en dehors du protéasome sont aussi connues : LYTAC, pour des chimères détournant la dégradation de protéines extracellulaires vers les lysosomes, et MADTAC, pour des chimères détournant la dégradation par macroautophagie. Plusieurs techniques, en particulier des plates-formes de criblage, la modélisation mathématique et la conception computationnelle sont utilisées pour le développement de nouveaux PROTAC efficaces.
Subject(s)
COVID-19 Drug Treatment , Drug Design , Molecular Targeted Therapy/methods , Proteolysis , Recombinant Fusion Proteins/pharmacology , SARS-CoV-2/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Autophagy , Catalysis , Humans , Lysosomes/metabolism , Neoplasm Proteins/antagonists & inhibitors , Neoplasms/drug therapy , Proteasome Endopeptidase Complex/metabolism , Protein Conformation , Protein Processing, Post-Translational/drug effects , Protein Stability , Proteolysis/drug effects , RNA/drug effects , RNA-Binding Proteins/antagonists & inhibitors , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/pharmacokinetics , Structure-Activity Relationship , Ubiquitin-Protein Ligases/metabolism , UbiquitinationABSTRACT
BACKGROUND: The spring 2020 COVID-19 epidemic severely impacted France's healthcare system. The associated lockdown (17 March- 11 May 2020) and the risk of exposure to SARS-CoV-2 led patients to change their use of healthcare. This article presents the development and implementation of a real-time system to monitor i) private doctors' activity in South-eastern France, and ii) changes in prescription of drugs for people with diabetes, mental health disorders and for certain vaccines from Mars 2020 to October 2020. METHODS: Data extracted from the regional healthcare insurance databases for 2019 and 2020 were used to construct indicators of healthcare use. They were calculated on a weekly basis, starting from week 2 2020 and compared for the same period between 2019 and 2020. RESULTS: Private doctors' activity decreased during the spring 2020 lockdown (by 23 % for general practitioners and 46 % for specialists), followed by an almost complete return to normal after it ended until week 41. Over the same period, a huge increase in teleconsultations was observed, accounting for 30 % of private doctors' consultations at the height of the crisis. The start of the lockdown was marked by a peak in drug prescriptions, while vaccinations declined sharply (by 39 % for the measles, mumps and rubella (MMR) vaccine in children under 5 years old, and by 54 % for human papillomavirus vaccine in girls aged 10-14 years old). CONCLUSION: The ongoing COVID-19 epidemic may lead to health consequences other than those directly attributable to the disease itself. Specifically, lockdowns and foregoing healthcare could be very harmful at the individual and population levels. The latter issue is a concern for French public authorities, which have implemented actions aimed at encouraging patients to immediately seek treatment. However, the COVID-19 crisis has also created opportunities, such as the roll-out of teleconsultation and tele-expertise. The indicators described here as part of the monitoring system can help public decision-makers to become more responsive and to implement tailored actions to better meet the general population's healthcare needs.
Subject(s)
COVID-19/epidemiology , Patient Acceptance of Health Care , Drug Prescriptions/statistics & numerical data , France/epidemiology , Humans , Private Practice/trends , Telemedicine/trends , Vaccination/statistics & numerical dataABSTRACT
On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. The outbreak caused a worldwide impact, becoming a health threat to the general population and its professionals. To date, there are no specific antiviral treatments or vaccines for the COVID-19 infection, however, some drugs are being clinically tested. The use of these drugs on large scale raises great concern about their imminent environmental risk, since the elimination of these compounds by feces and urine associated with the inefficiency of sewage treatment plants in their removal can result in their persistence in the environment, putting in risk the health of humans and of other species. Thus, the goal of this work was to conduct a review of other studies that evaluated the presence of the drugs chloroquine, hydroxychloroquine, azithromycin, ivermectin, dexamethasone, remdesivir, favipiravir and some HIV antivirals in the environment. The research indicated the presence of these drugs in the environment in different regions, with concentration data that could serve as a basis for further comparative studies following the pandemic.
ABSTRACT
BACKGROUND: Starting in spring 2020, the COVID-19 pandemic markedly impacted the French healthcare system. Lockdown and risks of exposure to the coronavirus induced patients to modify their ways of use. The objective of this article was to share feedback on the implementation of a real-time monitoring system concerning (a) the activity of private practitioners in southeastern France, and (b) the evolution of reimbursements for drugs prescribed to persons with diabetes, for treatment of mental health disorders, and for performance of some vaccines. METHODS: Data regarding 2019 and 2020 were extracted from regional health insurance databases. They were used to elaborate several indicators relative to the general health insurance scheme, which were calculated and updated each week, starting with week 2. RESULTS: We observed a drop in private physician activity during the lockdown (-23% for general practitioners; -46% for specialist doctors), followed by a return to a semblance of normalcy. Concomitantly, a boom in teleconsultations occurred: at the height of the crisis they represented 30% of medical acts. The initial stage of the lockdown was characterized by peak provisioning for drugs, whereas vaccination strongly declined (-39% regarding measles, mumps and rubella vaccine among children aged less than 5 years; -54% regarding human papillomavirus vaccine among girls aged 10 to 14 years). CONCLUSION: The COVID-19 pandemic could lead to health effects other than those directly attributable to the coronavirus itself. Renouncing care may result in healthcare delays highly deleterious for people and society. Public authorities are preoccupied with these questions; they have set up action plans aimed at encouraging patients to seek treatment without delay. That said, the COVID-19 pandemic crisis has also created opportunities, such as the expansion of telemedicine. Although partial, these indicators can provide useful information enabling public decision makers to be reactive and to implement specific actions to meet the health needs of the population.
Subject(s)
COVID-19 , Delivery of Health Care/organization & administration , Primary Health Care , Adolescent , Adult , Aged , Child , Female , France , Humans , Insurance, Health , Male , Middle Aged , Young AdultABSTRACT
Coronavirus disease 2019 (COVID-19) has resulted in the death of over 18â 000 Canadians and has impacted the lives of all Canadians. Many Canadian research groups have expanded their research programs to include COVID-19. Over the past year, our knowledge of this novel disease has grown and has led to the initiation of a number of clinical vaccine and drug trials for the prevention and treatment of COVID-19. Here, we review SARS-CoV-2 (the coronavirus that causes COVID-19) and the natural history of COVID-19, including a timeline of disease progression after SARS-CoV-2 exposure. We also review the pathophysiological effects of COVID-19 on the organ systems that have been implicated in the disease, including the lungs, upper respiratory tract, immune system, central nervous system, cardiovascular system, gastrointestinal organs, the liver, and the kidneys. Then we review general therapeutics strategies that are being applied and investigated for the prevention or treatment of COVID-19, including vaccines, antivirals, immune system enhancers, pulmonary supportive agents, immunosuppressants and (or) anti-inflammatories, and cardiovascular system regulators. Finally, we provide an overview of all current Health Canada authorized clinical drug and vaccine trials for the prevention or treatment of COVID-19.