INTRODUCTION:Giant cell arteritis (GCA) is a large-vessel vasculitis occurring in people aged over 50 years. Recent studies have shown that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, is remarkably effective in treating GCA and allows significant dose sparing of glucocorticoids. However, it makes it difficult to monitor disease activity. Furthermore, treatment is often prolonged over 1 year due to the fear of relapse after stopping TCZ and/or the absence of an optimal discontinuation scheme. METHODS AND ANALYSIS:This study aims at comparing two discontinuation regimens in a population of GCA patients who have been treated with TCZ for 12-36 months and have discontinued glucocorticoids for at least 12 weeks. Patients will be randomised with a 1:1 ratio between two arms: immediate discontinuation (cessation) versus gradual discontinuation of TCZ (162 mg subcutaneously every 2 weeks for 12 weeks and then every 4 weeks for 12 additional weeks). Patients will be followed up for 78 weeks. The primary endpoint is relapse-free survival after 26 weeks of follow-up. A total of 120 patients will be randomised (60 in each group) for a period of 3 years. ETHICS AND DISSEMINATION:The trial was approved by an independent ethics committee (CPP Sud Ouest et Outre Mer IV) and the French health authority (French National Agency for Medicines and Health Products Safety-ANSM) through the Clinical Trials Information System (CTIS) provided by the European Medicines Agency (EMA). The informed consent complies with the ICH GCP guideline and regulatory requirements. Eligible patients may only be included in the study after providing informed consent. Findings will be published in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER:NCT06037460.

Giant cell arteritis (GCA) is a large-vessel vasculitis occurring in people aged over 50 years. Recent studies have shown that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, is remarkably effective in treating GCA and allows significant dose sparing of glucocorticoids. However, it makes it difficult to monitor disease activity. Furthermore, treatment is often prolonged over 1 year due to the fear of relapse after stopping TCZ and/or the absence of an optimal discontinuation scheme. This study aims at comparing two discontinuation regimens in a population of GCA patients who have been treated with TCZ for 12–36 months and have discontinued glucocorticoids for at least 12 weeks. Patients will be randomised with a 1:1 ratio between two arms: immediate discontinuation (cessation) versus gradual discontinuation of TCZ (162 mg subcutaneously every 2 weeks for 12 weeks and then every 4 weeks for 12 additional weeks). Patients will be followed up for 78 weeks. The primary endpoint is relapse-free survival after 26 weeks of follow-up. A total of 120 patients will be randomised (60 in each group) for a period of 3 years. The trial was approved by an independent ethics committee (CPP Sud Ouest et Outre Mer IV) and the French health authority (French National Agency for Medicines and Health Products Safety—ANSM) through the Clinical Trials Information System (CTIS) provided by the European Medicines Agency (EMA). The informed consent complies with the ICH GCP guideline and regulatory requirements. Eligible patients may only be included in the study after providing informed consent. Findings will be published in peer-reviewed journals and conference presentations. NCT06037460 .

Objectives: Increasing evidence has suggested the benefits of dexmedetomidine in patients with sepsis. Dexmedetomidine may increase vasopressor sensitivity, which may be of interest in the setting of refractory septic shock. The α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS) pilot study aimed to evaluate the effect of dexmedetomidine on the vasopressor response in patients with refractory septic shock. Design: This study was a multicenter, randomized, placebo-controlled, double-blind pilot trial. Setting: The study was conducted in 5 ICUs in France. Patients: Inclusion criteria were septic shock (Sepsis-3 definition) and norepinephrine requirement greater than or equal to 0.25 µg/kg/min (0.5 µg/kg/min of norepinephrine tartrate) with persistent circulatory failure (defined by lactate > 2 mmol/L, oliguria, or skin mottling) and invasive mechanical ventilation. Interventions: The arterial pressure response to phenylephrine was measured before starting the treatment (0 hr), at 6 hours (primary outcome), and 12 hours. In the treatment arm, dexmedetomidine was given at a fixed dose of 1 µg/kg/hr. Measurements and Main Results: Inclusions were stopped early because of higher mortality in the dexmedetomidine arm. Thirty-two patients of the 36 planned were included. Response to phenylephrine at 6 hours was lower in the dexmedetomidine group than in the placebo group (1.26 ± 0.23 vs. 1.45 ± 0.26; p = 0.048), although this difference was also observed at baseline ( p = 0.029). There were no significant differences between the groups in terms of cumulative norepinephrine dose, lactatemia, Sequential Organ Failure Assessment score, fluid balance, ventilation-free days, or occurrence of bradycardia. Mortality on day 3 was higher in the dexmedetomidine group than in the placebo group, with a difference that diminished and was no longer significant on 30 and 90 days. Conclusions: Patients in the dexmedetomidine arm had a significantly lower response to phenylephrine at all study times including baseline, which might have contributed to higher early mortality in the dexmedetomidine arm and preclude to conclude on dexmedetomidine efficacy in refractory septic shock. However, heart rate was not decreased in the dexmedetomidine arm.

Introduction Acute pneumonia (AP) remains a leading cause of death in the older population. Excess risk of death after AP is partly due to cardiovascular (CV) events. We aim to evaluate whether aspirin at a preventive dose (100 mg daily) introduced at the acute phase of AP reduces 90-day mortality.Methods and analysis The ASPirin for Acute Pneumonia in the elderlY study is a phase III multicentre randomised double-blind, placebo-controlled, superiority clinical trial, which will investigate the efficacy and safety of aspirin in older patients with AP hospitalised in a French university and non-university hospitals. Patients will be randomised in a 1:1 ratio between two groups receiving daily either 100 mg of aspirin or a placebo, within 84 hours following radiologically proven AP diagnosis for 90 days. This study aimed at assessing the efficacy of aspirin on all-cause mortality after AP at 90 days (D90) (primary objective), D30 and D120 after randomisation, CV mortality, major adverse CV events (MACE) (ie, myocardial infarction, stroke, heart failure, new atrial fibrillation and pulmonary embolism, CV death and sudden death) incidence, length of intensive care unit and hospital stay, unscheduled rehospitalisation, dependence, overall and MACE-free survival, as well as safety outcomes (bleeding incidence). The sample size, calculated considering a 90-day mortality of 25% and a reduction of 10% in the aspirin group, a two-sided alpha risk at 5% and power of 80%, is 500 patients to prove the superiority of aspirin over placebo. To account for screening failures and consent withdrawals, 600 patients (300 per arm) will be included.Ethics and dissemination This study has full approval from an independent Ethics Committee. Participants will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.Trial registration number EU CTIS: 2024-510811-32-00.

ContexteLa littératie est définie comme « l’aptitude à lire, comprendre et utiliser l’information écrite ou orale dans la vie quotidienne ». Appliquée à la santé, elle est composée de différents domaines : la littératie en santé fonctionnelle, communicative et critique. L’amélioration du niveau de littératie en santé est actuellement une préoccupation nationale et internationale. L’intervention des équipes de recherche clinique et des pharmaciens cliniciens auprès des patients inclus dans un essai clinique nécessite la prise en compte de ce facteur individuel pour optimiser leur prise en charge. Une adaptation des outils de communication utilisés par ces équipes pluridisciplinaires est envisageable.ObjectifsL’objectif principal de ce travail était d’évaluer le niveau de littératie en santé des patients en essai clinique. L’objectif secondaire était de construire des outils pédagogiques d’accompagnement des patients participant à un essai clinique.MéthodeLes patients inclus étaient des patients adultes participant ou ayant participé à un essai clinique de type RIPH 1, RIPH 2 ou RIPH 3 (recherches impliquant la personne humaine), ayant donné leur consentement, suivis en endocrinologie ou en ophtalmologie. Le questionnaire de mesure de la littératie utilisé était le Functional, Communicative and Critical Health Literacy scale (FCCHL-HLS14), validé en langue française, et comportant 14 questions. Le score global obtenu était exprimé sur 70 points. L’analyse descriptive a permis de décrire les variables quantitatives avec leurs moyennes et leurs écarts-types, leurs médianes et leurs intervalles interquartiles ; et les variables qualitatives avec leurs effectifs et proportions exprimées en pourcentages. Un groupe de travail multidisciplinaire a ensuite choisi puis créé les outils pédagogiques.RésultatsAu total, 100 patients ont été inclus, l’âge médian était de 71 ans (IQR : 54–77), 55 % étaient des hommes, 33 % avaient un niveau d’études supérieur au BAC. Le score moyen de littératie globale observé était de 50/70 (écart-type : 10,0). Les scores moyens de littératie fonctionnelle, communicative et critique étaient respectivement de 18/25 (écart-type : 5,0), 19/25 (écart-type : 4,9), et 13/20 (écart-type : 4,3). Cinquante-sept pour cent des patients présentaient un niveau de littératie élevé. Deux types d’outils ont été proposés permettant de transmettre les idées clefs concernant les essais cliniques aux patients susceptibles de participer à un essai clinique : un support papier, et un support numérique composé de plusieurs capsules vidéo.Discussion/ConclusionDans notre étude la proportion de patients ayant un niveau de littératie élevée est largement supérieur au niveau retrouvé dans la population française, ce qui est cohérent avec les données de la littérature. Les outils proposés seront utiles au quotidien. L’impact de nos interventions pharmaceutiques sur le niveau de la littératie sera à évaluer à court, moyen et long terme au cours de prochaines études.

Introduction The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function PIK3CA variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3Kα-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS). During its development, in patients with the MCAP subgroup of PROS, there was no specific, standardised evaluation of the effect on neuro-cognitive functioning. Moreover, it remains unknown if the molecule crosses the blood-brain barrier. Our objective is to evaluate the efficacy of a 24 month treatment with alpelisib on adaptive behaviour in patients with MCAP syndrome.Methods and analysis SESAM is an industry-sponsored two-period multicentre French academic phase II trial, with a 6-month double-blind, placebo-controlled period followed by an open-label period. The primary endpoint is a ≥4-point improvement in the Vineland II Adaptive Behaviour Scale (VABS), 24 months after treatment initiation. Secondary objectives are safety, VABS improvement at 6 months, impact on the quality of life, epilepsy and hypotonia. 20 patients aged 2 to 40 years with an MCAP diagnosis and neurodevelopmental disorders of various degrees, will be followed monthly in local centres, centrally assessed (clinical, biological, neuropsychological and functional evaluation) at baseline and every 6 months. Patients will be evaluated by volumetric MRI at baseline and at 24 months. An optional lumbar puncture will be performed to investigate blood-brain barrier crossing. Inclusions were completed by April 2024, with the end of follow-up in November 2026.Given the efficacy of alpelisib in patients with PROS, if the drug crosses the blood-brain barrier, we can expect a clinical benefit for patients with neurocognitive disorders.Ethics and dissemination Ethical approval was given by CPP Sud-Ouest et Outre-Mer I (reference: 2022-500197-34-01). Findings from this study will be disseminated via publication, reports and conference presentations.Trial registration number NCT05577754

Introduction > The evolution of pharmacotherapeutic management of cancer patients makes essential the role of the community pharmacist through its management conducted in community pharmacy as well as its relationships with the hospital and primary care professionals. The objective of this work is to study this pharmacotherapeutic management, for all routes of administration considered. Methods > This observational study is based on a questionnaire and semi -structured interviews conducted with community pharmacists in contact with the Unite medicale ambulatoire de cancerologie (UMAC) of the University Hospital of Dijon. Results > The main objective of community pharmacists is to ensure that patients understand and comply with their treatment. Twenty-one percent of them have already implemented oral anticancer drug interviews. Sixty-five percent have partial information about the injectable treatments administered to their patients while only 3 % have complete knowledge. Sixty-nine percent of community pharmacists are satisfied with the documents sent by the UMAC (summary of drug treatments, pharmaceutical report, individualized pharmaceutical plan). However, the lack of information from hospital structures generally represents one of the main difficulties in the management of cancer patients by community pharmacists and coordination with other professionals. Discussion > The information and training of community pharmacists represent possible improvements for a better care and coordination between healthcare professionals. Some emerging practices, such as the implementation of oral anticancer drug interviews in community pharmacies and the participation of community pharmacists in primary care coordination organizations, also represent opportunities to strengthen their role in the management of cancer patients.

Introduction The increasing number of oral anticancer medicines (OAMs) dispensed in community pharmacies and the associated challenges (misuse, management of side effects) give the community pharmacist (CP) a major role in the pharmacotherapeutic management of cancer patients. In France, as a response to these challenges, cancer outpatients can schedule a meeting with their CP to ensure the safe and effective use of OAMs. The objectives of this study were to evaluate the perspectives of these interventions regarding their implementation and the opinion of French CPs. Methods A declarative survey and semi-structured interviews were conducted with CPs that dispensed at least one OAM between January 2021 and March 2022. The study was conducted between April and August 2022. Results Eighty-five CPs completed the survey. Of these pharmacists, 21% ( n = 18) had already performed OAM interventions and 91% ( n = 61) wanted to implement them. Lack of time, knowledge and training were the main barriers to implementation. No correlations were identified between the characteristics of community pharmacies and the likelihood of implementing OAM interventions. Conclusions Considering that CPs seem willing to implement them and the favourable context in France, this observational study highlights the potential of OAM interventions to improve the management of cancer patients. Though further studies are required to better evaluate the implementation and the potential effects of these interventions, OAM interventions could be relevant strategies in other healthcare systems to secure the management of cancer patients through the involvement of the CP.

L’évolution de la prise en charge pharmacothérapeutique des patients atteints de cancer rend primordial le rôle du pharmacien officinal à travers sa prise en charge à l’officine, mais aussi ses relations avec l’hôpital et les autres acteurs des soins primaires. L’objectif de ce travail est d’étudier cet accompagnement pharmacothérapeutique, et ce, pour toutes voies d’administration confondues. Cette étude observationnelle repose sur un questionnaire et des entretiens semi-directifs menés auprès de pharmaciens officinaux en relation avec l’Unité médicale ambulatoire de cancérologie (UMAC) du Centre hospitalier universitaire de Dijon. Les pharmaciens cherchent en premier lieu à garantir la bonne compréhension et l’observance du traitement. Vingt et un pour cent d’entre eux ont déjà instauré des entretiens anticancéreux oraux. Soixante-cinq pour cent ont une information partielle sur les traitements injectables administrés. Seuls 3 % en ont une connaissance complète. Soixante-neuf pour cent des pharmaciens sont satisfaits des documents transmis par l’UMAC (synthèse des traitements médicamenteux, compte rendu pharmaceutique, plan pharmaceutique personnalisé). Toutefois, le manque d’informations venant des structures hospitalières représente de façon générale une des principales difficultés pour l’accompagnement à l’officine et la coordination avec les autres professionnels. Des pistes envisageables pour un meilleur accompagnement par les pharmaciens officinaux et une meilleure coordination entre professionnels relèvent de l’information et de la formation des pharmaciens officinaux. Certaines pratiques émergentes, comme la réalisation d’entretiens anticancéreux oraux en officine, mais aussi la participation des officinaux aux dispositifs de coordination des soins de ville, représentent également des opportunités pour renforcer leur rôle dans ce parcours de soins. The evolution of pharmacotherapeutic management of cancer patients makes essential the role of the community pharmacist through its management conducted in community pharmacy as well as its relationships with the hospital and primary care professionals. The objective of this work is to study this pharmacotherapeutic management, for all routes of administration considered. This observational study is based on a questionnaire and semi-structured interviews conducted with community pharmacists in contact with the Unité médicale ambulatoire de cancérologie (UMAC) of the University Hospital of Dijon. The main objective of community pharmacists is to ensure that patients understand and comply with their treatment. Twenty-one percent of them have already implemented oral anticancer drug interviews. Sixty-five percent have partial information about the injectable treatments administered to their patients while only 3 % have complete knowledge. Sixty-nine percent of community pharmacists are satisfied with the documents sent by the UMAC (summary of drug treatments, pharmaceutical report, individualized pharmaceutical plan). However, the lack of information from hospital structures generally represents one of the main difficulties in the management of cancer patients by community pharmacists and coordination with other professionals. The information and training of community pharmacists represent possible improvements for a better care and coordination between healthcare professionals. Some emerging practices, such as the implementation of oral anticancer drug interviews in community pharmacies and the participation of community pharmacists in primary care coordination organizations, also represent opportunities to strengthen their role in the management of cancer patients.

Alors que l’attention était focalisée sur la prise en charge des patients atteints de COVID-19, les conséquences potentiellement négatives des confinements successifs chez les patients atteints de maladies chroniques ont été peu explorées. L’objectif de notre étude est d’évaluer l’impact du premier confinement lié à la COVID-19 chez les patients atteints de maladies chroniques en termes d’adhésion médicamenteuse, accès aux soins, règles hygiénodiététiques et santé mentale. Une étude de cohorte prospective téléphonique a été conduite entre le 14 avril 2020 et le 2 juin 2020 auprès de patients ambulatoires tirés au sort aléatoirement dans l’une des 8 cohortes (ou registres) régionales suivantes : artérite à cellules géantes, insuffisance cardiaque, dégénérescence maculaire liée à l’âge, fibrose pulmonaire idiopathique/hypertension artérielle pulmonaire, hémopathie maligne, hémophilie, sclérose en plaques, syndrome coronarien chronique. La non-adhésion médicamenteuse était définie comme une modification délibérée de la prise d’un ou plusieurs médicaments par le patient en dehors de tout avis médical, pharmaceutique ou infirmier. La détresse psychologique d’un patient était définie par un score ≥ 5 sur l’échelle Kessler Psychological Distress Scale K61. Un consentement oral était obtenu pour chaque participant à l’étude COVID-19 Lockdown Effects On Chronic Diseases (CLEO-CD ; NCT04390126). La population finale de l’étude comprenait 1274 patients d’âge moyen 66 ± 17 ans dont 55 % d’hommes. L’adhésion médicamenteuse était de 98 %. Les principales classes/molécules concernées par une non-adhésion des patients étaient : agents anticancéreux/immunosuppresseurs, anti-inflammatoires non stéroïdiens, antiangiogéniques, aspirine antiagrégante, inhibiteurs de l’enzyme de conversion. Parmi les 738 patients ayant au moins un rendez-vous médical programmé pendant la période, 305 (41 %) ont déclaré que le rendez-vous avait été annulé pour une raison qui n’était pas de leur ressort. Les principales modifications hygiénodiététiques étaient une détérioration du sommeil (qualité et/ou quantité ; 71 %), une augmentation > 25 % du temps passé devant un écran (46 %), une diminution de plus de 25 % de l’activité physique (46 %). Une détresse psychologique était présente chez 19 % des patients. En analyse multivariée, un habitat urbain (OR 1,76 [vs rural, < 2000 habitants] ; IC95 % 1,3–2,3 ; p = 10−4) et une détresse psychologique (OR 1,52 [vs score K6 < 5] ; IC95 % 1,1–2,2 ; p = 0,03) étaient des facteurs indépendants associés à la présence d’au moins un facteur délétère pour la santé des patients. Nos résultats sont rassurants en termes d’adhésion médicamenteuse. Chez les patients atteints de maladie chronique, une attention particulière est requise pour leur suivi s’ils habitent en milieu urbain et/ou s’ils présentent une détresse psychologique.

Abstract Background The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. Methods The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. Discussion This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. Trial registration ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

BACKGROUND:We conducted a systematic review of studies investigating lock solutions for use in non-tunneled hemodialysis catheters.METHODS:We searched PubMed and Cochrane databases from inception to June 11, 2021. Study inclusion criteria were: randomized trial or observational study, adults (>18 years), with acute kidney injury (AKI); and temporary non-tunneled catheters. We recorded bleeding events, catheter dysfunction and complications.RESULTS:Of 649 studies identified, 6 were included (4 randomized, 1 non-randomized trial, 1 retrospective cohort study; sample sizes 78-1496 patients). Citrate was compared to heparin in 4 studies, to saline in 1, and ethanol versus saline in 1. Event-free survival of non-tunneled catheters did not differ between groups. Catheter-related infections and adverse events were less frequent with citrate locks, but reached statistical significance in only two studies.CONCLUSION:Existing data are too heterogeneous to enable recommending one type of catheter lock over any other for non-tunneled hemodialysis catheters.

Le pharmacien de PUI (pharmacie à usage intérieur) en charge des aspects pharmaceutiques des essais cliniques joue un rôle central dans la gestion et le bon usage des produits de santé expérimentaux (PSE), en application des bonnes pratiques cliniques et conformément au Code de la santé publique. Le groupe Essais Cliniques de la CPCHU (Commission des Pharmaciens de CHU) s'est fixé comme objectif d'élaborer un guide national de recommandations visant à décrire ces activités et l'implication du pharmacien quel que soit le type d'établissement de santé. Après analyse de l'existant, des critères de fond et de forme ont été définis et le plan du guide construit. La rédaction des chapitres s'est effectuée en sous-groupes de travail, avec révision et validation systématiques en plénière. Le guide professionnel composé de 109 pages est disponible au format pdf interactif sur les sites de la SFPC et du CNCR. Les thématiques abordées sont regroupées en 4 chapitres, avec présence d'encarts de recommandations et/ou d'illustrations. Le document compte 374 références dont 329 textes réglementaires et 5 annexes. Le guide s'inscrit dans une démarche de diffusion, de sécurisation et d'homogénéisation des pratiques, afin d'aider les pharmaciens de PUI dans la gestion des PSE et dans le développement et/ou l'amélioration de leurs propres systèmes de performance en terme de qualité. Son format pédagogique en fait également un outil de formation des étudiants, des préparateurs et des pharmaciens séniors. Sa mise à jour régulière est nécessaire. The hospital pharmacist, in charge of the pharmaceutical aspects of clinical trials plays a central role in the management and the proper use of investigational health products (IHP), in accordance with the Good Clinical Practices and Public Health Code. The working group "Clinical trials" of the CPCHU (French University Hospitals Pharmacists' Commission) aimed to prepare national guidelines to describe the activities and involvement of the pharmacists, whatever the type of health care institution. After an analysis of the existing literature, form and content requirements were set and the structure was established. The chapters were written in subgroups, with systematic revision and validation in plenary. The professional guidelines are composed of 109 pages and are available as an interactive pdf file on the SFPC and CNCR websites. Topics covered in the guidelines are divided into 4 chapters, and include inserts of specific recommendations and/or some illustrations. There are 374 references, including 329 regulatory texts, and 5 appendices. These guidelines are a part of process of dissemination, standardization and securing practices, in order to help hospital pharmacists in the management of IHP and in the development or improvement of their own performance systems in terms of quality. Its pedagogical format also makes it a training tool for students, compounders and senior pharmacists. Its regular updating is necessary.

Background In older patients, multiple chronic conditions lead topolypharmacy which is associated with a higher risk of adverse drug events. Nowadays, the medication exposure of older patients with bleeding disorders has been poorly explored. Aim The aim of this study was to assess the prevalence of polypharmacy and the medication regimen complexity in older community-dwelling patients with hemophilia or von Willebrand Disease (VWD). Method The M'HEMORRH-AGE study (Medication in AGEd patients with HEMORRHagic disease) is a multicenter prospective observational study. Community-dwelling patients over 65 years with hemophilia or VWD were included in the study. The rate of polypharmacy (use of 5 to 9 drugs daily) and excessive polypharmacy (use of 10 or more medications daily) was assessed. The complexity of prescribed medication regimens was assessed using the Medication Regimen Complexity Index (MRCI). Results Overall, 142 older community-dwelling patients with hemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 (5.8) years). Prevalence of polypharmacy and excessive polypharmacy were 40.8% and 17.6%, respectively. The mean MRCI score was 16.9 (6.1). The mean MRCI score related to bleeding disorders medications was 6.9 (1.1). There was no significant difference between older hemophilia patients and VWD patients. Conclusion The M'HEMORRH-AGE study showed that more than half of older community-dwelling patients were affected by polypharmacy. In addition, the high medication regimen complexity in this older population suggests that interventions focusing on medication review and deprescribing should be conducted to reduce polypharmacy with its negative health-related outcomes.

Background. Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19. Methods. We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days. Results. Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation. Conclusions. SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients.

Introduction Refractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial. Methods This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee “Sud-Est VI” (2019-000726-22) and patients will be included after informed consent. Discussion The present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients. Trial registration Registered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.