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O presente texto discorre sobre a organização, desenvolvimento e resultados do projeto de extensão intitulado “Curso de extensão em Direitos Humanos para professores da rede pública de educação básica de Florianópolis e região”, que vem sendo desenvolvido desde 2019. O projeto tem por objetivo central a organização de cursos de formação continuada para docentes da educação básica pública do município de Florianópolis e região metropolitana. O curso foi iniciado de forma presencial no início de 2020, com uma etapa de formação sendo realizada em uma Escola Estadual. Com o advento da pandemia de Covid-19, as atividades do projeto precisaram ser adaptadas para o formato remoto, com a organização de ciclos de debates virtuais sobre direitos humanos ao longo de 2020 e 2021 e de um curso online em 2021. Neste período, o curso contribuiu para a capacitação de centenas de profissionais da educação básica, no âmbito dos Direitos Humanos.

Introduction CDK4/6 inhibitors, such as palbociclib, are prescribed in association with hormonal therapy in metastatic breast cancer patients. In Phase II/III studies, high neutropenia occurred in more than one in two patients leading to significant dose reductions, palbociclib interruptions and additional hematological samplings. Like most oral targeted drug, therapeutic drug monitoring (TDM) may be of interest for monitoring plasma exposition and optimize their dosage. We evaluated the correlation of this toxicity with palbociclib pharmacokinetics (PK), and classical sources of PK variabilities. Materials and method This is an open-label biomarker study conducted in subjects with first-line ER+/HER2- metastatic breast cancer treated with a palbociclib-aromatase inhibitor association (NCT04025541). Primary endpoint was the correlation between palbociclib trough concentration (Ctrough) at day 15 of first cycle of treatment (D15C1) and incidence of grade 3/4 neutropenia, within the first two months of treatment. Secondary endpoints included the analysis of variables associated with grade 3/4 neutropenia, with D15C1 palbociclib Ctrough values, and correlations with genetic polymorphisms in selected genes involved in palbociclib PK. Co-medications were collected to assess drug-drug interactions (DDI) risk and the potential impact on palbociclib PK. Results 58 patients, with mean age of 62.9 years, were included and followed up for 1 year. Clinicopathological variables were classical for the setting. One third of the population was taking concurrently a CYP3A4 and/or Pgp inhibitor, and one fourth an anti-acid medication, drugs that may interact with palbociclib. High-grade neutropenia occurred in 67.2% of patients (70.7% all grade neutropenia). One third of patients required a dose reduction, mainly for hematological toxicity. The geometric median of palbociclib plasma Ctrough was 74.1 ng/ml (interquartile range 61.3 - 101.5). Other covariates influencing the PK of palbociclib were significant in the univariate analysis. Indeed, while age > 65.5 years old (median) and reduced renal function (< 88.5 ml/min, median) were correlated with increased palbociclib concentration (p=0.003 and p=0.017, respectively) in univariate analysis. In multivariate analysis, higher neutrophil counts at inclusion (HR=0.54 for each 109/L increase in neutrophils count, range 0.33 - 0.87, p=0.002) while higher (>74.1 ng/mL, HR 5.51, range 1.10 - 27.6, p=0.024) plasma concentration of palbociclib were the only 2 variables correlated with the incidence of neutropenia. PK of palbociclib is closely related to co-medications, with majored exposition in CYP3A4 inhibitor cohort (106 vs 71.3 ng/ml, p=0.031, HR 0.22) or reduced exposition in anti-acid cohort (72.2 vs 80 ng/ml, p= 0.016, HR -0.27). Lastly, the homozygote G/G allele of the NRI2 (PXR) variant (Rs10934498) was associated with reduced palbociclib concentration (p=0.031) in univariate analysis. Conclusion We have characterized PK/toxicity correlation of palbociclib, regarding high-grade neutropenia. D15C1 higher palbociclib Ctrough is associated with the occurrence of high-grade neutropenia. As drug-drug interaction appears to be the most relevant source of palbociclib Ctrough variability in our cohort, a special attention must be paid to comedications in this population of patients. This is the first prospective study which characterizes biomarkers of toxicity associated with palbociclib treatment. Therapeutic drug monitoring can be a tool to limit high grade toxicities under palbociclib. Citation Format: Fanny Leenhardt, Frédéric Fiteni, Ludovic Gauthier, Marie Alexandre, Séverine Guiu, Nelly Firmin, Stéphane Pouderoux, Chloé Gautier, Gerald Lossaint, Alexandre Payen, Celine Gongora, Litaty Mbatchi, Alexandre Evrard, William Jacot. Pharmacokinetic determinants of palbociclib hematological toxicity [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-23.

La présente étude vise à caractériser certaines résistances thermiques locales liées à la transmission de chaleur le long d'assemblages de câbles de puissance et de connecteurs électriques (appelés par la suite harnais électriques). Dans certains cas, de tels harnais peuvent en effet générer des ponts thermiques amenant de la chaleur d'un point chaud vers un élément devant être maintenu à basse température. Au contraire, dans une configuration où l'auto échauffement du harnais lié au passage du courant pose des problèmes de fiabilité, des résistances thermiques locales importantes peuvent être à l'origine de zones de surchauffes indésirables. Dans tous les cas, la connaissance des résistances thermiques associées peut s'avérer cruciale pour assurer la fiabilité de l'assemblage. Dans cet objectif, un dispositif expérimental de caractérisation thermique de harnais électriques a été construit. Celui-ci est constitué d'une source chaude à dissipation de puissance contrôlée et d'une source froide à température imposée par un écoulement d'eau thermostaté circulant dans un échangeur. Le harnais électrique et son connecteur associé se placent entre ces deux éléments afin d'y imposer un flux de chaleur longitudinal. L'insertion d'une succession de thermocouples le long de l'assemblage permet d'évaluer les évolutions longitudinales de température et de flux de chaleur pour en déduire ainsi les différentes résistances thermiques recherchées. Dans les travaux présentés ici, deux géométries de harnais particulières sont investiguées. Dans un premier temps, la résistance de contact thermique liée au sertissage d'un câble multibrins en cuivre dans une pièce usinée faite du même matériau (nommée « splice » par la suite) est évaluée. Par la suite, la résistance thermique induite par un connecteur électrique détachable usiné dans deux barreaux de cuivre est mesurée. En parallèle de ces mesures, des modèles de conduction 3D reproduisant les conditions expérimentales ont été construits à l'aide d'un solveur commercial (6SigmaET). L'objectif est, par comparaison entre le modèle et l'expérience, d'identifier les résistances thermiques locales liées aux contacts thermiques, difficilement accessibles par les mesures à disposition étant données les géométries complexes considérées. Dans le cas du sertissage, il apparait que la résistance thermique liée à celui-ci reste faible devant les résistances thermiques de conduction liées à l'assemblage câble/splice et est donc difficilement identifiable. Au contraire, pour ce qui est du connecteur démontable, la résistance thermique liée au passage du flux au niveau du contact mécanique local entre les deux parties du connecteur est bien plus significative. La comparaison entre l'expérience et la modélisation 3D permet ainsi de fournir une estimation satisfaisante de la résistance thermique locale liée à la connexion électrique. En conclusion, il est important de noter que les premières conclusions évoquées dans cette communication restent très spécifiques aux harnais étudiés. Ainsi, des essais complémentaires sur un grand nombre de configurations restent à mener pour envisager l'établissement à terme de règles de conception utiles à l'ingénieur.

Introduction Le ventricule droit systémique (VDs), associé à une physiologique biventriculaire, est un ventricule de morphologie droite en position sous aortique, qui assume la circulation systémique. Cette configuration se retrouve dans la dextro-transposition des gros vaisseaux (DTGV) après chirurgie d’atrioseptopexie (AS) ainsi que dans la Levo-transposition des gros vaisseaux (LTGV). Malgré une survie leur permettant d’atteindre l’âge adulte, les patients avec VDs vont développer de nombreuses complications. Objectifs Ce travail vise à analyser le phénotype complexe de ces patients, en définissant la prévalence et les caractéristiques de l’hypertension pulmonaire (HTP) tardive, et en identifiant les mécanismes sous-jacents de la mort subite. Nous étudierons la problématique de la variabilité inter et intra-observateurs dans l’évaluation par ETT du VDs. Résultats Une cohorte de 214 patients avec VDs est suivie à l’ICM, 140 avec DTGV et AS, et 74 avec LTGV. Article 1: Une collecte de données rétrospective a été menée pour les 140 patients adultes avec DTGV et AS. Une HTP, post-capillaire dans tous les cas, a été détectée chez 54.5% patients ayant subi un cathétérisme cardiaque, et chez 76.5% lorsque le cathétérisme cardiaque était réalisé pour bilan d’insuffisance cardiaque. Les patients avec HTP étaient plus susceptibles de développer des arythmies auriculaires et ventriculaires, de nécessiter une hospitalisation pour insuffisance cardiaque et une intervention sur la valve tricuspide. La mortalité était significativement plus élevée chez les patients atteints d'HTP. Article 2: Parmi les 140 patients avec DTGV et AS, 8 (6 %) ont présenté un arrêt cardiaque d'étiologie arythmique présumée. Aucun n'avait d’histoire de maladie coronarienne, d'arythmie ventriculaire soutenue ou de syncope. Pour les 5 patients dont les circonstances entourant l’arrêt cardiaque ont été documentées, 3 décès sont survenus à l'effort, 1 après une consommation de méthamphétamine et 1 lors d'une tachyarythmie auriculaire. Des autopsies, réalisées chez 2 patients, ont révélé un infarctus aigu du myocarde massif du VDs avec des artères coronaires normales et des lésions ischémiques sous-endocardiques chroniques. Article 3: Des observateurs indépendants (6) ont interprété rétrospectivement 44 ETT précédemment acquises pour 25 DTGV et AS, et 19 LTGV. Les images de 10 patients ont été réinterprétées à un mois d'intervalle. La concordance inter-observateurs et intra-observateurs a été démontrée bonne à excellente pour les mesures quantitatives telles que le diamètre basal et longitudinal, la « fractionnal area change» et l’aire télédiastolique et télésystolique. La concordance inter-observateurs était faible pour la caractérisation de la sévérité des dimensions et de la fonction du VDs (normale, légère, modérée ou sévère), mais avec une concordance intra-observateurs bonne à excellente. Ces résultats suggèrent que l'appréciation globale des dimensions et de la fonction du VDs repose sur une interprétation variable des mesures quantitatives. Conclusion L'HTP post-capillaire d'apparition tardive est fréquente chez les adultes avec DTGV et AS, et est associée à un pronostic défavorable. L’ischémie myocardique à coronaires saines favorisée par des fréquences cardiaques élevées est l’un des mécanismes conduisant à la mort subite dans le VDs. Pour une évaluation adéquate en ETT, il semble nécessaire d'établir des seuils clairs pour les paramètres quantitatifs., Introduction A systemic right ventricle (sRV) is present when the morphological RV supports the systemic circulation, and the morphological left ventricle supports the pulmonary circulation. This configuration occurs in patients with complete transposition of the great arteries (TGA) after an atrial switch operation (AS) and in congenitally corrected transposition of the great arteries (ccTGA). Despite good survival in childhood, sRV is associated with severe morbidity and a shortened lifespan during adulthood. Objectives This work aims to analyze the complex phenotype of these patients by assessing the prevalence and characteristics of late-onset pulmonary hypertension (PH) and the underlying mechanisms of sudden cardiac death. Echocardiographic evaluation of sRV remains challenging, we will determine the inter- and intra-observer variability of sRV size and function echocardiographic parameters. Results A cohort of 214 patients with sRV is followed at Montreal Heart Institute, 140 patients with TGA and AS and 74 patients with ccTGA. Article 1: A retrospective cohort study was conducted on 140 adults with TGA and AS. PH was detected in 54.5% of patients who had invasive hemodynamic studies, 76.5% of patients who had cardiac catheterization for heart failure. PH was post-capillary in all. Patients with PH were more likely to develop atrial and ventricular arrhythmias, require hospitalizations for heart failure and undergo tricuspid valve surgery. Mortality was significantly higher in patients with PH. Article 2: Of the 140 patients, 8 (6%) had a cardiac arrest of presumed arrhythmic etiology. None had established coronary artery disease, sustained ventricular arrhythmias, or syncope. For 5 patients in whom circumstances surrounding the arrests were documented, 3 occurred on exertion, 1 after consuming recreational methamphetamine, and 1 in the context of an atrial tachyarrhythmia. Autopsies were performed in 2 of 5 patients. Both revealed acute massive myocardial infarction of the hypertrophied sRV with normal coronary arteries and chronic subendocardial ischemic lesions. Article 3: Independent observers (6) retrospectively interpreted 44 previously acquired echocardiograms in 25 TGA/AS and in 19 ccTGA. Images from 10 patients (5 TGA/AS and 5 ccTGA) were reinterpreted at one month interval. Quantitative parameters included inlet and longitudinal diameters, systolic and diastolic areas fractional area change (FAC) and wall thickness. sRV dilatation and function were qualitatively graded as normal, mild, moderate or severe. Interobserver and intraobserver agreement was good to excellent for sRV diameters, areas and FAC, except for the sRV wall thickness. Interobserver agreement was poor for the qualitative assessment of sRV size and function but with a good to excellent intraobserver agreement. These findings suggest that overall appreciation of sRV size and function relies on variable interpretation of measurements by observers. Conclusion Late-onset post-capillary PH is highly prevalent in adults with TGA and atrial switch surgery and is associated with an adverse prognosis. Myocardial ischemia exacerbated by high heart rates (exercise, supraventricular arrhythmias) is one of the mechanisms leading to sudden death in sRV. For an adequate echocardiography evaluation of the sRV, It seems necessary to establish clear thresholds for quantitative parameters and a validated algorithm.

Contents 1. Dataset - Full dataset of all 78 animals infected with different strains of SARS-CoV-2 2. Monolix files - Structural models of the 5 models used - mlxtran files of the 6 models used 3. R script files - Main script used to reproduce all figures and results in the article - File used to store functions used in the main script - Result file of the simulations

In clinical trials, longitudinal data are commonly analyzed and compared between groups using a single summary statistic such as area under the outcome versus time curve (AUC). However, incomplete data, arising from censoring due to a limit of detection or missing data, can bias these analyses. In this article, we present a statistical test based on splines-based mixed-model accounting for both the censoring and missingness mechanisms in the AUC estimation. Inferential properties of the proposed method were evaluated and compared to ad hoc approaches and to a non-parametric method through a simulation study based on two-armed trial where trajectories and the proportion of missing data were varied. Simulation results highlight that our approach has significant advantages over the other methods. A real working example from two HIV therapeutic vaccine trials is presented to illustrate the applicability of our approach.

The definition of correlates of protection is critical for the development of next-generation SARS-CoV-2 vaccine platforms. Here, we propose a model-based approach for identifying mechanistic correlates of protection based on mathematical modelling of viral dynamics and data mining of immunological markers. The application to three different studies in non-human primates evaluating SARS-CoV-2 vaccines based on CD40-targeting, two-component spike nanoparticle and mRNA 1273 identifies and quantifies two main mechanisms that are a decrease of rate of cell infection and an increase in clearance of infected cells. Inhibition of RBD binding to ACE2 appears to be a robust mechanistic correlate of protection across the three vaccine platforms although not capturing the whole biological vaccine effect. The model shows that RBD/ACE2 binding inhibition represents a strong mechanism of protection which required significant reduction in blocking potency to effectively compromise the control of viral replication.

L'article traduit une préoccupation quant à la complexification des situations de travail du XXIesiècle. Prenant appui sur un modèle de développement de compétences durables inscrit en didactique professionnelle, dix personnes expérimentées en soudage-montage ont participé à une recherche qualitative sur le processus de travail. Une démarche d’analyse de contenu a permis de décrire les paliers décisionnels et opérationnels des activités clés, ainsi que des paramètres de sécurité, de métier et de conformité associés aux actions du processus de raisonnement en soudage-montage. Les résultats illustrent des manifestations de l’intelligence professionnelle en soudage-montageet l’interdépendance de la professionnalisation, de l’employabilité et du partenariat.

Background: The CDK4/6 inhibitors palbociclib is prescribed in association with hormonal therapy for the management of metastatic breast cancer patients. Like most oral targeted drug, therapeutic drug monitoring may be used for personalize their dosage. Using a recently published dosing technique (LC-MS/MS), we aimed at evaluating the correlation between first-cycle palbociclib plasma exposition and co-medications in order to evaluate drug-drug interaction (DDI) impact under palbociclib treatment.Methods: This is an open-label phase 4 study conducted in female subjects with first-line metastatic breast cancer (NCT04025541) treated with a palbociclib-aromatase inhibitor association. Plasma concentration of palbociclib was assessed at 24 hours postdose (plasma trough concentration Ctrough) at day 15 of first cycle of treatment. A dedicated pharmacist consultation allowed the determination of clinical covariates of interest, such as weight, body surface area, ethnicity, food intake, co-medications use and DDI before Palbociclib initiation and retrospectively at the end of clinical trial. Patients were classified then according to their risk of DDI potentially leading to inhibition of CYP3A4 and/or P-glycoprotein and gastric pH increase by gastric acid-suppressive (GAS) agents (such as proton pump inhibitors, histamine H2-receptor blockers or alginic acid). Relevant drug known to have an inhibition of CYP3A4 and/or P-glycoprotein or pH-modification activity were checked in databases (e.g. DDI predictor®, Drugs.com®, Pubmed®). Results: To date, after Ctrough analysis of the 35 first cases, the geometric mean (± standard deviation [min-max]) of palbociclib plasma Ctrough was 79.5 ng/ml (± 26.1% [43.6 ng/mL - 133 ng/mL]) at day 15, similar to what reported in the PALOMA trials. No correlation between plasma concentration and body weight, body area or also age of the patients was found in our cohort. Regarding ethnicity, all the included patients were from Caucasian origin. 31% of patients (11/35) were identified of taking drugs that could cause DDI CYP3A4 and P-glycoprotein inhibition mediated (amlodipine n=3, simvastatin n=3, losartan n=2, fluconazole n=1, atorvastatin n=1, ivabradine n=1). These potential DDI interactions were associated with a significantly higher palbociclib concentration DDI subgroup (102 ng/mL vs 69 ng/mL) (p=0.000272) (Table 1). No CYP3A4 and/or P-glycoprotein inductor were reported in cohort. 1.4% of patients (5/35) were identified of taking GAS agents (pantoprazole n=2, ranitidine n=2, alginic acid n=1). We found a significantly reduction of palbociclib concentration (59.2 ng/mL vs 79.8 ng/mL) (p=0.048) in patients taking GAS medications (Table 1). Conclusion : These preliminary results, in real-life settings, obtained with our recently-published HPLC-MS/MS method, give important information on palbociclib monitoring and pharmacokinetic variability. DDI appear to have a significant impact on palbociclib plasma exposure, GAS agents are already know to modified palbociclib absorption. Additional studies are needed to characterize palbociclib plasma concentration variations between patients, and their clinical impact on efficacy and safety. The study is ongoing and will evaluate additional potential clinical and biological impact of DDI on neutropenia occurrence, on a larger population of patients. Table 1: Patients’ plasma palbociclib concentration (day 15 of cycle 1 of treatment).Plasma palbociclib concentrations (ng/ml), global cohort (n=35)Geometric mean (CV%) (min;max)79.5 (26.1%) (43.6;133)Plasma palbociclib concentrations (ng/ml), cohort with DDI CYP3A4 and P-gp mediated (n=11)Geometric mean (CV%)102 (24.3%)Plasma palbociclib concentrations (ng/ml), cohort without DDI CYP3A4 and P-gp mediated (n=24)Geometric mean (CV%)69 (19.8%)Plasma palbociclib concentrations (ng/ml), cohort with GAS treatment (n=5)Geometric mean (CV%)59.2 (15.9%)Plasma palbociclib concentrations (ng/ml), cohort without GAS treatment (n=30)Geometric mean (CV%)82.9 (26.1%) Citation Format: Fanny Leenhardt, Matthieu Gracia, Catherine Perrin, Claudia Muracciole-Bich, Bénédicte Marion, Celine Roques, Marie Alexandre, Nelly Firmin, Stephane Pouderoux, Litaty Mbatchi, Celine Gongora, William Jacot, Alexandre Evrard. Impact of drug-drug interaction on palbociclib serum levels: Interest of therapeutic drug monitoring [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-16.

Ce texte de réflexion vise à problématiser la transition « formation en présence – formation à distance » à l’université en lien avec les enjeux didactiques et politiques qui se profilent au temps de la COVID‑19, marqué par l’urgence d’agir. Le concept pivot mobilisé est celui de « transition », lié à la problématique des temporalités dans les sciences humaines et sociales. Sur la ligne du temps de la formation à distance, cette pandémie se présente comme un évènement de rupture qui aura un impact structurant et durable sur la formation à distance à l’université., This text (critical perspective) aims to problematize the transition from face-to-face education to distance education at the university in relation to the didactic and political issues that emerged at the time of COVID‑19, which was marked by the urgency to act. The concept mobilized is that of “transition,” linked to the problem of temporalities in the human and social sciences. In the timeline of distance education, this pandemic is presented as a breakthrough event that will have a structuring and lasting impact on distance education in universities.

The definition of correlates of protection is critical for the development of next generation SARS-CoV-2 vaccine platforms. Here, we propose a new framework for identifying mechanistic correlates of protection based on mathematical modelling of viral dynamics and data mining of immunological markers. The application to three different studies in non-human primates evaluating SARS-CoV-2 vaccines based on CD40-targeting, two-component spike nanoparticle and mRNA 1273 identifies and quantifies two main mechanisms that are a decrease of rate of cell infection and an increase in clearance of infected cells. Inhibition of RBD binding to ACE2 appears to be a robust mechanistic correlate of protection across the three vaccine platforms although not capturing the whole biological vaccine effect. The model shows that RBD/ACE2 binding inhibition represents a strong mechanism of protection which required significant reduction in blocking potency to effectively compromise the control of viral replication.One Sentence SummaryA framework for modelling the immune control of viral dynamics is applied to quantify the effect of several SARS-CoV-2 vaccine platforms and to define mechanistic correlates of protection.

PURPOSE: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. METHODS: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2- MBC who received ET or CT first. RESULTS: We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9-13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1-13.4), HR 0.96 (95% CI 0.90-1.01, P = 0.1277). CONCLUSIONS: PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance.

International audience; GaN transistors are limited in their operational capabilities due to some limitations, of which the thermal management aspects. Until now, most of the existing heat-dissipator systems using additive manufacturing (AM) are based on a metallic finned heat sink, which is heavy and has a relatively high thermal resistance. Heat dissipation based on a phase change as operated in heat pipes is more efficient. Such heat sinks have been experimented with metals or ceramics and not by now with polymers. However, this may be of great interest. The use of polymer may enable reducing weight and cost of the thermal device. It may allow also improving the chemical compatibility of the heat pipe material and fluid, as this is often a severe issue. This work presents a characterization of a 3D-printed polymer-based heat pipe evaporator intended for GaN transistors. The electronic copper circuit on the polymer surface is created using plastronics technology. The metallized circuit presents an adequate electrical conductivity. The thermal characterization performed with the HFE 7000 fluid, shows that it is actually possible to cover the entire heated polymer wall with active nucleation sites once the full developed nucleate boiling regime is reached. The heat conduction through the insulating polymer wall appears as the limiting phenomenon for heat transfer.

The decision to administer adjuvant chemotherapy in treatment of early invasive breast cancer (EBC) is often complex, particularly for hormone receptor-positive (HR+) diseases, and current guidelines often classify these patients in an intermediate-risk group. Several biomarkers are currently available in this indication, in order to obtain additional and more accurate prognostic information compared to classic clinicopathological characteristics and guide the indication of adjuvant chemotherapy, optimizing the efficacy/toxicity ratio. We conducted a systematic review to evaluate the clinical validity and clinical utility of five biomarkers (uPA/PAI-1, OncotypeDX®, MammaPrint®, PAM50, and EndoPredict®) in HR+/HER2- EBC, whatever the nodal status. A total of 89 studies met the inclusion criteria. Even though data currently available confirm the clinical validity of these biomarkers, there is a lack of data regarding clinical utility for most of them. Prospective studies in well-defined populations are needed to integrate these biomarkers in a decision strategy.

Pharmacist consultation is unfrequently performed in oncology clinical trials that include patients who often have many co-treatments increasing the risk of drug–drug interactions (DDI). The aim of this study was to determine whether best possible medication history (BPMH) by hospital pharmacist at inclusion and therapeutic drug monitoring could be used for DDI risk evaluation and for current oral targeted therapy management. A prospective clinical trial (ALCINA 2, NCT04025541) was carried out in metastatic breast cancer cohort treated by palbociclib to conduct pharmacokinetics-toxicity correlation study. BPMH was prospectively performed by the hospital pharmacist at each trial inclusion, followed by a contact to the patient’s community pharmacy to complete the collected data. Pharmacokinetic analysis was performed on blood samples collected at day 15 of cycle 1 of palbociclib treatment. Pharmacist interventions indicated that at inclusion, current medications were incomplete for 63% of the enrolled patients (32/51). It allowed the real-time management of high-risk DDI detected in third of patients. The palbociclib Ctrough geometric median (min–max) was significantly higher in cohort with potential DDI [106 ng/mL (66.7–113)], than cohort without potential DDI [70.1 ng/mL (54.1–89.7)], p = 0.0284. This is the first prospective study evaluating the relevance of proactive BPMH by pharmacist with contact to the community pharmacy during the inclusion step of a clinical trial to ensure the efficacy and safety of the investigated drug. This investigation was thus able to highlight the statistically significant impact of these DDI on palbociclib plasma concentration variation during the clinical trial. Clinicaltrials.gov identifier NCT04025541.

Born out of the desire of a generous donor and his children to honour the memory of a loved one, a team of representatives from Montréal Sacré-Coeur Hospital Foundation (MSCHF), employees of the Hôpital en santé mentale Albert-Prévost (HSMAP), and administrators of both Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Nord-de-l'Île-de-Montréal and Collège d'enseignement général et professionnel (CÉGEP) de Saint-Laurent was formed to offer musical scholar performances to the HSMAP's clientele. Duos of different backgrounds (classical, popular and jazz), made up of student musicians, were selected to play on a weekly basis, alternating between two floors of the hospital. This article wishes to recount how an innovative and intersectoral project was organized to offer a simple moment of musical listening to HSMAP's hospitalized clientele, and what positive impacts have been identified to date. A look at a project that was initially very personal, but with a very collective impact.