β2GP1 antibodies.In contrast, this neutralizing effect was not observed when incubated with prothrombin fragment 1.Conclusion(s): Our data show that LAC-positive anti-prothrombin antibodies recognize prothrombin fragment 2. We were able to neutralize a prothrombin-dependent LAC with fragment 2 and with a novel nanobody directed against fragment 1.2.

Les paramètres pharmacocinétiques du cabotegravir et de la rilpivirine injectables sont peu connus, malgré leur impact sur le risque d'échec virologique. L'objectif était de déterminer les concentrations résiduelles de cabotegravir et rilpivirine chez les patients initiant ce traitement, et les facteurs de risque pour des concentrations basses. Nous avons inclus de façon prospective tous les patients débutant un traitement par cabotegravir et rilpivirine injectables dans deux hôpitaux universitaires. Pour être éligibles, les patients devaient avoir une charge virale VIH < 50 copies/mL depuis au moins 6 mois, ne pas avoir de résistance majeure aux INI ou INNTI (sauf K103N), et être immunisés contre le virus de l'hépatite B. Une phase d'instauration orale (cabotegravir 30 mg et rilpivirine 25 mg par jour durant 4 semaines) était réalisée dans un seul centre, et les injections intramusculaires de cabotegravir 600 mg et rilpivirine 900 mg étaient administrées à la première visite, à 4 et à 12 semaines, avec dosage de la charge virale VIH et des taux plasmatiques résiduels de cabotegravir et rilpivirine. Une concentration basse était définie à 1120 ng/mL pour le cabotegravir et 32 ng/mL pour la rilpivirine (premiers quartiles dans les essais), et nous avons étudié l'impact de l'âge, du sexe, de l'origine, de l'IMC et de la phase d'instauration orale sur le risque d'avoir un taux bas. Du 1er mars 2022 au 31 janvier 2023, 58 patients ont été inclus, avec 51 hommes (87.9%), et un âge médian de 31 ans. La plupart (43, 74.1%) étaient des hommes ayant des relations sexuelles avec des hommes, 13 (22.4%) étaient hétérosexuels et 2 (3.4%) avaient une toxicomanie intraveineuse. Cinq (8.6%) avaient un IMC ≥30 kg/m2. La plupart (35, 60.3%) avait un sous-type viral B et 2 (3.4%) avaient un sous-type à risque d'échec (A1). La durée médiane d'indétectabilité du VIH était de 8 ans et le taux médian de CD4 était 694/mm3. Avec un suivi médian à 36 semaines, nous avons observé un échec (1.7%), deux arrêts pour douleur (3.4%), et un décès (1.7%) non lié au traitement. Les taux résiduels médians de cabotegravir étaient 976 ng/mL (IQR 706 – 1434) à S4 et 701 ng/mL (IQR 440 – 1087) à S12, avec respectivement 35 (60.3%) et 43/56 (76.8%) patients sous le seuil de 1120ng/mL. Les taux résiduels médians de rilpivirine étaient 48 ng/mL (IQR 29 – 66) à S4 et 43 ng/mL (IQR 32 – 55) à S12, avec respectivement 16 (27.6%) et 15/56 (26.8%) patients sous le seuil de 32 ng/mL. Les facteurs de risque identifiés pour une concentration basse de cabotegravir étaient l'IMC (p=0.009 à S4) et la phase d'instauration orale (p=0.02 à S4, p=0.03 à S12), aucun n'était significatif pour la rilpivirine. Le patient en échec (charge virale VIH à 2820 copies/mL à S4) n'avait pas de mutation de résistance mais un IMC à 29.4 kg/m2, et des taux de cabotegravir et rilpivirine respectivement à 28 et 701 ng/mL à S4. Devant le risque de concentration faible de cabotegravir, nos données sont en faveur d'une phase d'instauration orale, en particulier chez les patients avec un IMC ≥30 kg/m2. Aucun lien d'intérêt

Summary In the medication management process, storage methods constitute a step at risk of errors that needs to be secured. As part of an institutional project, computerized medicine cabinets (CMC) have been deployed in our hospital???s emergency and intensive care units. In order to meet the requirements of the certification, the deployment of CMC in all care units has been decided. Each deployment includes many steps and involves several trades that must be coordinated. We decided to formalize these steps in the form of a checklist. Two pharmacists listed all the tasks required to install a CMC. They were ordered chronologically, and a person responsible for each step is proposed. All those involved in the installation of CMC in the care units validated the checklist. The checklist is broken down into 13 major steps, from the assessment of the need to the installation of CMC in the care units. Before installation, several months are required, particularly in terms of the delivery time of the CMC. Support and training for the pharmacy technicians and caregivers are essential to ensure the teams enrolment. By better implying and empowering all intervenants, directed by the pharmacist, the checklist provides to dynamise and to frame the CMC deployment. Moreover, it contributes to save time ?? 2021 Acad??mie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

L’approvisionnement en immunoglobulines humaines normales (IgHN) est en tension régulière depuis près de 15 ans. La rareté de la matière première, le délai de fabrication et une augmentation des consommations accentuée par le contexte de pandémie, en sont à l’origine. Face à ces difficultés, l’Agence Nationale de Sécurité du Médicament a diffusé une hiérarchisation des indications permettant de prioriser les IgHN. Son utilisation est parfois complexe, notamment dans les indications dépendant de critères clinico-biologiques et/ou à des lignes de traitement antérieures. L’objectif de ce travail est d’évaluer l’adéquation entre les indications des IgHN renseignées dans les dossiers des patients et la hiérarchisation, dans différents centres hospitaliers français. Il s’agit d’une analyse rétrospective des critères de hiérarchisation des IgHN renseignés dans les dossiers médicaux de patients hospitalisés entre le 1er et le 30 octobre 2021 dans 5 indications, au sein de 7 centres hospitaliers de différentes régions. Les indications étudiées et les critères associés sont : polyneuropathie inflammatoire démyélinisante chronique (PIDC) et myasthénie auto-immune grave (MAIG) avec recours à la plasmaphérèse en 1re intention ; purpura thrombopénique de l’adulte (PTIa) avec respect du score de Khellaf ; PTI de l’enfant (PTIe) avec respect du score de Buchanan > 3 ou taux de plaquettes < 10 G/L ; déficit immunitaire secondaire (DIS) dont myélome et allogreffe de cellules souches hématopoïétiques avec infections récentes à répétition et/ou dosage pondéral des IgG conforme aux recommandations. Les critères ont été retrouvés dans le dossier pour 61/172 patients (35 %), toutes indications étudiées confondues. Les critères sont retrouvés à un taux très variable selon l’indication : 5 % (3/61 patients) pour les PIDC et 10 % (2/19 patients) pour les MAIG, 40 % (6/15 patients) pour les PITa, 33 % (2/6 patients) pour les PTIe et 67 % (43/71 patients) sur au moins un des deux critères pour les DIS. Ce travail multicentrique illustre la difficulté de l’application stricte de la hiérarchisation. On observe un faible taux de critères de prescription des IgHN renseignés dans les dossiers patients. Pour 4 des 5 indications étudiées, le taux de conformité est inférieur à 50 %. Cependant, les dossiers patients peuvent ne pas être exhaustifs, notamment le recours à la plasmaphérèse (PIDC et MAIG). Le critère « infections récentes à répétitions » ne précise pas les délais ni les rythmes des infections. Il existe plusieurs interprétations possibles, une actualisation des recommandations pourrait intégrer des éléments plus explicites. Si la sensibilisation des prescripteurs est un levier pour un meilleur recueil des informations dans les dossiers médicaux, l’intégration de ces recommandations aux logiciels de prescription pourrait permettre aux pharmaciens une analyse optimisée. Il reste nécessaire de laisser primer l’avis des spécialistes dans certaines situations particulières.

INTRODUCTION:Treatment of cancer-associated thrombosis (CAT) requires specific approaches, although it is well codified in most cases. Current national and international (International Initiative on Cancer and Thrombosis, ITAC) Clinical Practice Guidelines (CPG) recommend the use of low-molecular-weight heparin (LMWH) over 6 months as first treatment option, and anticoagulation should be maintained thereafter as long as cancer is active. Since compliance improves when patients understand their disease and related treatments, we created a dedicated patient education program (PEP) for CAT, aiming to improve quality of care.METHODS:Retrospective analysis of all patients who voluntarily joined the PEP for CAT from 2014 to 2020.RESULTS:In total, 182 cancer patients (median age, 64.9 years) were included, 53.3% with metastatic disease. A total of 528 PEP sessions (median, 3 per patient) were delivered. After PEP completion, the rate of self-injections or those performed at home by a relative had increased from 49.1% to 59.8% (P=0.05). Quality of life had improved significantly (P=0.025) and 90.0% of patients reported adhering to anticoagulant therapy.CONCLUSION:Implementation of a structured and personalized PEP for CAT is feasible, allowing to improve cancer patient empowerment, adherence to CAT treatment and quality of life. The Groupe francophone et cancer (GFTC) members aim at facilitating access to CAT-PEP for both patients and caregivers and use of the multi-language ITAC-CPG mobile app (free access: www.itaccme.com) to improve the care and quality of life of patients with CAT.

Objectives. - Securing the supply of immunoglobulin is essential in indications without therapeutic alternatives, such as primary immunodeficiencies (PIDs). The objective was to obtain an inventory of patients with PID, and to quantify their immunoglobulin needs. Methods. - The retrospective study was conducted using data from January to June 2018, in Bordeaux, Lyon and Paris (Saint-Louis). Patients with PID were included based on the pharmaceutical traceability of the 3 centres. The concordance between the patients included and the patients in the CEREDIH register was analysed. Results.- For the 361 patients included (sex ratio: M/F 0.8; mean age: 45 +/- 20 years, mean weight: 62 +/- 19 kg), 2082 dispensations were performed for a total volume of 57 kg of immunoglobulin. Of the 108 specialty changes identified, 68% were due to supply tensions. In total, the analysis of CEREDIH data made it possible to identify 727 patients with PID and followed up once in the study centres, 161 of whom were recorded in the 2 data follow-ups (patients included and CEREDIH). Conclusions. - A complete overview of immunoglobulin needs in PIDs is difficult to obtain. Supply tensions have been observed although PIDs are a priority indication. Measures must be proposed to ensure an adequate supply regardless of the location of patients in the territory. (C) 2020 Academie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

•Des difficultés d’approvisionnements en Ig ont été observées dans les DIP.•La vision exhaustive des besoins en Ig dans les DIP est difficile à obtenir.•Le parcours de soins doit être considéré pour sécuriser les dispensations d’Ig.

Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients after tumor progression. The treatment of CAT is challenging because of a high risk of VTE recurrence, a high risk of bleeding, common presence of comorbidities, poly-medication, and potential drug-drug interactions (DDI). Since 2018, direct oral anticoagulants (DOACs) represent a promising therapeutic alternative and have been recently included into the 2019 update of the International Initiative on Thrombosis and Cancer (ITAC-CME) clinical practice guidelines for management of CAT. However, pharmacokinetic studies suggest that concomitant treatment with P-gp or CYP3A4 inhibitors will result in an increased exposure to rivaroxaban and apixaban, but the clinical relevance of these studies is unknown. In addition, there is an important inter-individual variability in drug absorption, distribution, metabolism and elimination, even more in cancer patients. Overall, the risk of pharmacokinetic DDI should be estimated based on several individual (patient age, renal and liver function, number of comedications) and diseases-related factors, including inflammation, sarcopenia, and low body weight. In this context, DDI with clinical implications could be expected with anti-neoplastic agents or supportive care treatments, especially with drugs known to be moderate or strong inhibitors/inducers of CYP3A4 and P-gp. Consequently, in the presence of potential DDIs through CYP3A4, and/or P-gp, LMWHs remain the first-line anticoagulant of choice for the long-term treatment of CAT. Multidisciplinary consultation meetings and therapeutic patient education should be emphasized in the complex management of CAT.

Background Venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and severe complication in cancer patients, which is the second leading cause of death in this population. International guidelines recommend a low-molecular weight heparin (LMWH)-based treatment during at least 3 months and until chemotherapy begins. The pharmacy and the internal medicine department have developed a patient education programme (PEP) dedicated to patients treated for cancer-associated thrombosis (CAT). Purpose The objective of PEP is to increase adherence and compliance to long term-treatment, to strengthen the autonomy and to prevent or limit the recurrent VTE or bleeding complications. We describe our cohort of patients and the impact of the PEP programme. Material and methods From 2014 to 2017, data were retrieved from the electronic patient files. A minimum number of sessions for each patient was set at three, allowing funding by our supervisory authorities. Characteristics of the patients, the number of PEP sessions, anticoagulant, recurrences and bleeding were collected. Results In the programme, 48 patients were included. The main cancers represented were breast cancer (35%) and lung cancer (13%). Sixty per cent of cancers were metastatic at baseline, 44% of patients were diagnosed with DVT, 12% with catheter related-thrombosis and 44% with PE. Tinzaparin was prescribed in 86% of patients. The average number of sessions performed per patient was 3.5. Nearly 30% of patients did not have this minimum of three sessions, either because of death, treatment break or relay by another drug class. PEP sessions increased the self-injection rate from 40% to 67%, injections by another person from 9% to 12% and reduced the rate of injections by a nurse from 51% to 21%. Nearly 12% of patients had recurrent thrombosis under anticoagulant therapy. Only 4% of patients experienced a bleeding event. In more than 85% of cases, patients reported being observant. Conclusion The programme fulfilled its objectives, including understanding, treatment adherence and allowing patients to be more independent with injections. This programme is the first to describe a cohort of patients treated for CAT and the result of a good collaboration between physicians, pharmacists and nurses. References and/or acknowledgements No conflict of interest.

Background The non-adherence with medication regimens is a major public health issue. In kidney-transplanted patients, it results in late acute rejections and graft losses. Purpose The aim of this study was to identify noncompliant kidney-transplanted patients to their immunosuppressive drugs (ISD), thanks to a self-report instrument, an indirect measure of adherence. Material and methods From June to October 2017, our hospital's kidney-transplanted recipients answered to Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS). They were interviewed by a pharmacy resident before their consultation with a nephrologist. The self-report's recall period was limited to the last 4 weeks preceding the consultation. Five items were assessed: dose taking (missing a dose), drug holidays (missing two or more doses in a row), timing deviation (postponing 2 hours from the prescribed time), reduction of dose and persistence (stopping completely the intake of ISD). Results A total of 174 patients answered to the self-report: 37% (65/174) were noncompliant to their ISD. Among them, 18% (12/65) missed one to more than four doses, 62% (40/65) admitted they were used to postponing once to almost daily doses and 18% (12/65) combined both missing and postponing doses. One patient took drug holidays, two reduced their doses themselves and one stopped completely her ISD. Taking ISD at a fixed time was the most common difficulty. The major part of the noncompliant patients (78%) received an initial therapeutic education. This prospective study led by an external person to the transplant team enabled a high participation rate in a short period but excluded patients who did not speak local language. Conclusion This preliminary study highlighted a large number of transplanted patients who were noncompliant with their ISD. The results of the self-report will be combined with ISD blood levels, a direct measure of adherence. The study will also be deepened by the research of factors influencing the non-compliance. A closer monitoring must be developed as part of therapeutic education, especially for the noncompliant patients in a long-term follow-up. No conflict of interest

Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i. v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [+/- standard error of the mean (s. e. m.)] age of 39.2 (+/- 4) years, presented with familial partial lipodystrophy (n= 11, 10 women) or congenital generalized lipodystrophy (n= 5, four women). Their mean (+/- s. e. m.) BMI (23.9+/- 0.7 kg/m(2)), glycated haemoglobin levels (8.5+/- 0.4%) and serum triglycerides levels (4.6+/- 0.9 mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic-hyperinsulinaemic clamps, n= 4 and n= 12, respectively), insulin secretion during graded glucose infusion (n= 12), and acute insulin response to i. v. glucose adjusted to insulin sensitivity (disposition index, n= 12), significantly increased after 1 year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies.

Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex. We report and discuss herein five cases of major hemorrhagic complications under DOAC, which were reported to the pharmacological surveillance department over one year at Saint-Louis University Hospital (Paris, France). We further discuss the need for careful assessment of the risk/benefit ratio at time of starting DOAC therapy in daily clinical practice.

One hundred twenty-three children from 6 French centers were evaluated retrospectively for the treatment of steroid-refractory acute graft-versus-host disease (aGVHD) with Inolimomab, a murine anti-IL2R.