Faculté de pharmacie – Travaux et publications

URI permanent de cette collectionhttps://hdl.handle.net/1866/19189

Cette collection accueille les publications savantes et d’autres types de travaux d’auteur.e.s associé.e.s à cette unité. Voir aussi les collections Thèses et mémoires et Production étudiante de l'unité.

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Accès libre
Monoclonal antibodies and immunotherapy : theory and applications
Adam, Albert; Université de Montréal. Faculté de pharmacie (2024)
This document is an update of a previous one published on the Papyrus site of the University of Montreal in 2023. It takes into account new therapeutic targets as well as monoclonal antibodies approved last year by the FDA. This update consists of two parts. Firstly. the theoretical bases underlying the antigen-antibody reaction and therefore the effectiveness of active and passive immunotherapy. On the other hand, a description and classification of the 70 antigenic targets as well as their 150 corresponding monoclonal antibodies currently used for passive immunotherapy.
Accès libre
Anticorps monoclonaux et immunothérapie : théorie et applications
Adam, Albert; Université de Montréal. Faculté de pharmacie (2024)
Ce document est une mise à jour d’un précédent publié sur le site Papyrus de l’Université de Montréal en 2023. Il tient compte des cibles thérapeutiques nouvelles ainsi que des anticorps monoclonaux agréés l’an dernier par la FDA. Cette mise à jour comprend deux parties. D’une part. les bases théoriques qui sous tendent la réaction antigène-anticorps et donc l’efficacité de l’immunothérapie active et passive. D’autre part, une description et une classification des 70 cibles antigéniques ainsi que leurs 150 anticorps monoclonaux correspondants actuellement utilisés pour l’immunothérapie passive.
Accès libre
Deep tissue penetration of bottle-brush polymers via cell capture evasion and fast diffusion
Rabanel, Jean-Michel; Mirbagheri, Marziye; Olszewski, Mateusz; Xie, Guojun; Le Goas, Marine; Latreille, Pierre-Luc; Counil, Hermine; Hervé, Vincent; Oliveira Silva, Rummenigge; Zaouter, Charlotte; Adibnia, Vahid; Acevedo, Mariana; Servant, Marc; Martinez, Vincent A.; Patten, Shunmoogum A.; Matyjaszewski, Krzysztof; Ramassamy, Charles; Banquy, Xavier; Université de Montréal. Faculté de pharmacie (American Chemical Society, 2022-12-14)
Drug nanocarriers (NCs) capable of crossing the vascular endothelium and deeply penetrating into dense tissues of the CNS could potentially transform the management of neurological diseases. In the present study, we investigated the interaction of bottle-brush (BB) polymers with different biological barriers in vitro and in vivo and compared it to nanospheres of similar composition. In vitro internalization and permeability assays revealed that BB polymers are not internalized by brain-associated cell lines and translocate much faster across a blood–brain barrier model compared to nanospheres of similar hydrodynamic diameter. These observations performed under static, no-flow conditions were complemented by dynamic assays performed in microvessel arrays on chip and confirmed that BB polymers can escape the vasculature compartment via a paracellular route. BB polymers injected in mice and zebrafish larvae exhibit higher penetration in brain tissues and faster extravasation of microvessels located in the brain compared to nanospheres of similar sizes. The superior diffusivity of BBs in extracellular matrix-like gels combined with their ability to efficiently cross endothelial barriers via a paracellular route position them as promising drug carriers to translocate across the blood–brain barrier and penetrate dense tissue such as the brain, two unmet challenges and ultimate frontiers in nanomedicine.
Accès libre
Monoclonal antibodies and immunotherapy : theory and applications
Adam, Albert; Université de Montréal. Faculté de pharmacie (2023-06-27)
The primary goal of this course is to provide the theoretical background necessary to better understand the mechanism of immunotherapy and in particular the mode of action of monoclonal antibodies currently available in immunotherapy.
Accès libre
Anticorps monoclonaux et immunothérapie : théorie et applications
Adam, Albert; Université de Montréal. Faculté de pharmacie (2023-06-27)
Le but premier de ce cours est de fournir les bases théoriques nécessaires pour mieux comprendre les mécanismes de l’immunothérapie et en particulier le mode d’action des anticorps monoclonaux actuellement disponibles en immunothérapie.
Accès libre
(In)stability of ligands at the surface of inorganic nanoparticles : a forgotten question in nanomedicine?
Le Goas, Marine; Saber, Justine; González Bolívar, Sara; Rabanel, Jean-Michel; Awogni, Jean-Marc; Boffito, Daria C.; Banquy, Xavier; Université de Montréal. Faculté de pharmacie (Elsevier, 2022-06-14)
Multiple inorganic nanoparticles (NPs) are currently being developed for nanomedicine. Various core materials and shapes are explored, but they all display a common hybrid structure, with organic ligands on their surface. These ligands play a key role in the NP colloidal stability and surface properties, and therefore strongly impact the biological fate of the NPs. However, ligands may be subject to reorganization, degradation, desorption, and exchange, both during their shelf-life and upon exposure to a biological environment. The question of ligand (in)stability at the surface of inorganic NPs has been little addressed in the literature. The goal of this review is to provide a portrait of this critical phenomenon. We identify and review here the different mechanisms likely to promote ligand instability and discuss the resulting biological fate of ligands. This review is aimed to provide a better understanding of these phenomena and to help researchers to design NP-based medicines with better clinical efficacy and translation ability.
Accès libre
Short-sequence superadhesive peptides with topologically en-hanced cation-π interactions
Chang, Heng; Adibnia, Vahid; Li, Chuanxi; Su, Rongxin; Qi, Wei; Banquy, Xavier; Université de Montréal. Faculté de pharmacie (American Chemical Society, 2021-06-03)
In this study, using the surface force apparatus, we report engineered peptides with short sequences of phenylalanine (F) and lysine (K) amino acids capable of forming the most efficient cation−π interactions reported for underwater adhesive systems in the literature to date. This outstanding cation−π binding efficiency can be achieved between surfaces coated using these peptides when an isolated K amino acid is flanked by F amino acids in the peptide sequence. Surface force analysis and molecular dynamics (MD) simulation reveal that such a sequence of amino acids minimizes repulsive hydration forces that prevent effective cation−π interactions. The resulting peptides exhibit cation−π interactions that are 14 times more efficient than cation−π interactions between the homogenous films of F and K. In addition, the resulting adhesive energy of two surfaces covered with these peptides is more than twice larger than the best-performing underwater adhesive energy based on cation−π interactions. Such effects of molecular sequences on the binding efficiency of underwater adhesives suggest that a short sequence of amino acids, which is engineered to have effective cation−π interactions, can be sufficient to improve upon the adhesive performance of complex mixtures of macromolecules as underwater superadhesives. The results provided in this study allow to unambiguously rationalize the molecular determinants necessary for strong cation−π interactions and offer new guidelines for developing mussel-inspired underwater adhesive materials.
Accès libre
A quantitative UHPLC-MS/MS method for the growth hormone-releasing peptide-6 determination in complex biological matrices and transdermal formulations
Esposito, Cloé; García Ac, Araceli; Laszlo, Elise; Duy, Sung Vo; Michaud, Catherine; Sauvé, Sébastien; Ong, Huy; Marleau, Sylvie; Banquy, Xavier; Brambilla, Davide; Université de Montréal. Faculté de pharmacie (Elsevier, 2021-05-26)
Growth hormone-releasing peptide-6 (GHRP-6) is part of a group of small synthetic peptides with potent GH-releasing activity that have gained attention in the last two decades by virtue of their cyto- and cardioprotective effects. Despite numerous preclinical studies highlighting the potential cardiovascular benefits of GHRP-6, confirmation of clinical efficacy is still awaited. Recent advances in transdermal drug delivery systems have been made to address challenges related to the poor skin permeation rate of peptides by using pain-free microneedle (MN) devices. Accordingly, highly sensitive and validated analytical methods are required for the potential clinical translation of MN-based peptides. The ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) methods developed in this study aimed to quantify GHRP-6 in biological matrices (plasma, skin) and dissolving polymeric MNs. UHPLC/MS-MS method detection limits of 0.1, 1.1, 0.9 and 1.5 ng/mL were achieved in neat solution, plasma, MN polymer solution, and skin matrices, respectively. Method validation also involved assessment of precision, accuracy, limits of quantification, linearity of matched calibration curves (R2 > 0.990), extraction recovery, matrix effect, stability studies, selectivity, and carry-over effect. Additionally, quality control samples were analyzed at three concentration levels to determine recovery (85–109%) and accuracy/bias (3.2–14.7%). Intra- and inter-day precision were within the range of acceptance (RSDs of 3.0–13.9% and 0.4–14.5%, respectively). The validity and applicability of such methods were successfully demonstrated for transdermal GHRP-6 delivery using GHRP-6-loaded MN patches applied to pig skin.
Accès libre
Recent developments in natural and synthetic polymeric drug delivery systems used for the treatment of osteoarthritis
Rahimi, Mahdi; Charmi, Gholamreza; Matyjaszewski, Krzysztof; Banquy, Xavier; Pietrasik, Joanna; Université de Montréal. Faculté de pharmacie (Elsevier, 2021-01-12)
Osteoarthritis (OA), is a common musculoskeletal disorder that will progressively increase in older populations and is expected to be the most dominant cause of disability in the world population by 2030. The progression of OA is controlled by a multi-factorial pathway that has not been completely elucidated and understood yet. However, over the years, research efforts have provided a significant understanding of some of the processes contributing to the progression of OA. Both cartilage and bone degradation processes induce articular cells to produce inflammatory mediators that produce proinflammatory cytokines that block the synthesis of collagen type II and aggrecan, the major components of cartilage. Systemic administration and intraarticular injection of anti-inflammatory agents are the first-line treatments of OA. However, small anti-inflammatory molecules are rapidly cleared from the joint cavity which limits their therapeutic efficacy. To palliate this strong technological drawback, different types of polymeric materials such as microparticles, nanoparticles, and hydrogels, have been examined as drug carriers for the delivery of therapeutic agents to articular joints. The main purpose of this review is to provide a summary of recent developments in natural and synthetic polymeric drug delivery systems for the delivery of anti-inflammatory agents to arthritic joints. Furthermore, this review provides an overview of the design rules that have been proposed so far for the development of drug carriers used in OA therapy. Overall it is difficult to state clearly which polymeric platform is the most efficient one because many advantages and disadvantages could be pointed to both natural and synthetic formulations. That requires further research in the near future.
Accès libre
Phytoglycogen nanoparticles : nature-derived superlubricants
Adibnia, Vahid; Ma, Yingshan; Halimi, Ilias; Walker, Gilbert C.; Banquy, Xavier; Kumacheva, Eugenia; Université de Montréal. Faculté de pharmacie (American Chemical Society, 2021-05-07)
Phytoglycogen nanoparticles (PhG NPs), a single-molecule highly branched polysaccharide, exhibit excellent water retention, due to the abundance of close-packed hydroxyl groups forming hydrogen bonds with water. Here we report lubrication properties of close-packed adsorbed monolayers of PhG NPs acting as boundary lubricants. Using direct surface force measurements, we show that the hydrated nature of the NP layer results in its striking lubrication performance, with two distinct confinement-controlled friction coefficients. In the weak- to moderate-confinement regime, when the NP layer is compressed down to 8% of its original thickness under a normal pressure of up to 2.4 MPa, the NPs lubricate the surface with a friction coefficient of 10–3. In the strong-confinement regime, with 6.5% of the original layer thickness under a normal pressure of up to 8.1 MPa, the friction coefficient was 10–2. Analysis of the water content and energy dissipation in the confined NP film reveals that the lubrication is governed by synergistic contributions of unbound and bound water molecules, with the former contributing to lubrication properties in the weak- to moderate-confinement regime and the latter being responsible for the lubrication in the strong-confinement regime. These results unravel mechanistic insights that are essential for the design of lubricating systems based on strongly hydrated NPs.
Accès libre
Plasmon-free polymeric nanowrinkled substrates for surface-enhanced raman spectroscopy of two-dimensional materials
Mirbagheri, Marziye; Kaur, Jasneet; Pham, Hoang Vu; Adibnia, Vahid; Zarrin, Hadis; Banquy, Xavier; Hwang, Dae Kun; Université de Montréal. Faculté de pharmacie (American Chemical Society, 2020-12-21)
We report plasmon-free polymeric nanowrinkled substrates for surface-enhanced Raman spectroscopy (SERS). Our simple, rapid, and cost-effective fabrication method involves depositing a poly(ethylene glycol)diacrylate (PEGDA) prepolymer solution droplet on a fully polymerized, flat PEGDA substrate, followed by drying the droplet at room conditions and plasma treatment, which polymerizes the deposited layer. The thin polymer layer buckles under axial stress during plasma treatment due to its different mechanical properties from the underlying soft substrate, creating hierarchical wrinkled patterns. We demonstrate the variation of the wrinkling wavelength with the drying polymer molecular weight and concentration (direct relations are observed). A transition between micron to nanosized wrinkles is observed at 5 v % concentration of the lower molecular-weight polymer solution (PEGDA Mn 250). The wrinkled substrates are observed to be reproducible, stable (at room conditions), and, especially, homogeneous at and below the transition regime, where nanowrinkles dominate, making them suitable candidates for SERS. As a proof-of-concept, the enhanced SERS performance of micro/nanowrinkled surfaces in detecting graphene and hexagonal boron nitride (h-BN) is illustrated. Compared to the SiO2/Si surfaces, the wrinkled PEGDA substrates significantly enhanced the signature Raman band intensities of graphene and h-BN by a factor of 8 and 50, respectively.
Accès libre
Superswelling microneedle arrays for dermal interstitial fluid (prote) omics
Laszlo, Elise; De Crescenzo, Gregory; Nieto-Argüello, Alfonso; Banquy, Xavier; Brambilla, Davide; Université de Montréal. Faculté de pharmacie (Wiley, 2021-08-16)
The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.
Accès libre
Superlubricity of zwitterionic bottlebrush polymers in the presence of multivalent ions
Adibnia, Vahid; Olszewski, Mateusz; De Crescenzo, Gregory; Matyjaszewski, Krzysztof; Banquy, Xavier; Université de Montréal. Faculté de pharmacie (American Chemical Society, 2020-08-13)
In this study, we report lubrication properties of physisorbed zwitterionic bottlebrush polymers in the presence of multivalent ions using the surface force apparatus. Unlike polyelectrolyte brushes, the lubrication properties of which diminish drastically in the presence of multivalent ions at concentrations as low as 0.1 mM, zwitterionic bottlebrush polymers exhibit friction coefficients as low as ∼10−3 at such concentrations of multivalent ions up to intermediate normal loads. This lubrication ability persists until surface wear occurs at high normal loads. The surface wear is demonstrated to be triggered by the multivalent ions bridging the polymer chains and dehydrating the zwitterionic moieties. Finally, the analysis of the polymer film stability suggests that the partial desorption of polymers in the presence of the ions does not affect the lubrication performance. Therefore, even in the physisorbed state, zwitterionic brushes perform significantly better than covalently grafted polyelectrolyte brushes in the presence of multivalent ions.
Accès libre
Nanoparticle shell structural cues drive in vitro transport properties, tissue distribution and brain accessibility in Zebrafish
Rabanel, Jean-Michel; Faivre, Jimmy; Zaouter, Charlotte; Patten, Shunmoogum A.; Banquy, Xavier; Ramassamy, Charles; Université de Montréal. Faculté de pharmacie (Elsevier, 2021-08-24)
Zwitterion polymers with strong antifouling properties have been suggested as the prime alternative to polyethylene glycol (PEG) for drug nanocarriers surface coating. It is believed that PEG coating shortcomings, such as immune responses and incomplete protein repellency, could be overcome by zwitterionic polymers. However, no systematic study has been conducted so far to complete a comparative appraisal of PEG and zwitterionic-coating effects on nanoparticles (NPs) stealthness, cell uptake, cell barrier translocation and biodistribution in the context of nanocarriers brain targeting. Core-shell polymeric particles with identical cores and a shell of either PEG or poly(2-methacryloyloxyethyl phosphorylcholine (PMPC) were prepared by impinging jet mixer nanoprecipitation. NPs with similar size and surface potential were systematically compared using in vitro and in vivo assays. NPs behavior differences were rationalized based on their protein-particles interactions. PMPC-coated NPs were significantly more endocytosed by mouse macrophages or brain resident macrophages compared to PEGylated NPs but exhibited the remarkable ability to cross the blood-brain barrier in in vitro models. Nanoscale flow cytometry assays showed significantly more adsorbed proteins on PMPC-coated NPs than PEG-coated NPs. In vivo, distribution in zebrafish larvae, showed a strong propensity for PMPC-coated NPs to adhere to the vascular endothelium, while PEG-coated NPs were able to circulate for a longer time and escape the bloodstream to penetrate deep into the cerebral tissue. The stark differences between these two types of particles, besides their similarities in size and surface potential, points towards the paramount role of surface chemistry in controlling NPs fate likely via the formation of distinct protein corona for each coating.
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Sonochemical synthesis of porous gold nano- and micro-particles in a Rosette cell for drug delivery applications
Usen, Ndifreke; Dahoumane, Si Amar; Diop, Mamadi; Banquy, Xavier; Boffito, Daria C.; Université de Montréal. Faculté de pharmacie (Elsevier, 2021-09-05)
We report the synthesis of gold nano- and micro-particles that relies on α-D-glucose (C6H12O6) as the reducer and stabilizer in a Rosette cell under 20 kHz ultrasound irradiation. The chemical and physical effects of ultrasonic irradiation on the synthesis were investigated. The results showed that an optimum pH is required for the formation of insoluble Au(0) particles. Upon irradiation, low pH yielded gold nanoparticles while high pH resulted in microparticles. The Au surface capping by α-D-glucose hydroxyl and carbonyl groups was confirmed by Fourier transform infrared (FT-IR) spectroscopy. X-ray diffraction (XRD) analysis indicated that the Au particles crystallize within the face-centered-cubic (FCC) cell lattice. Moreover, intermittent sonication reduced larger amounts of the Au precursor compared to the continuous mode. Furthermore, tuning sonication time and mode influences the particle size and porosity as characterized by scanning and transmission electron microscopy. Our results shed a new light into the importance of the experimental and ultrasound parameters in obtaining gold particles of desired features through sonochemistry.
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The application of target trials with longitudinal targeted maximum likelihood estimation to assess the effect of alcohol consumption in adolescence on depressive symptoms in adulthood
Liu, Yan; Schnitzer, Mireille; Herrera, Ronald; Díaz, Iván; O’Loughlin, Jennifer; Sylvestre, Marie-Pierre; Université de Montréal. Faculté de pharmacie (Oxford University Press, 2023-12-07)
Time-varying confounding is a common challenge for causal inference in observational studies with time-varying treatments, long follow-up periods, and participant dropout. Confounder adjustment using traditional approaches can also be limited by data sparsity, weight instability and computational issues. The Nicotine Dependence in Teens (NDIT) study is a prospective cohort study involving 24 data collection cycles to date, among 1,294 students recruited from 10 high schools in Montreal, Canada, including follow-up into adulthood. Our aim is to estimate associations between the timing of alcohol initiation and the cumulative duration of alcohol use on depression symptoms in adulthood. Based on the target trials framework, we define intention-to-treat and as-treated parameters in a marginal structural model with sex as a potential effect-modifier. We then use the observational data to emulate the trials. For estimation, we use pooled longitudinal target maximum likelihood estimation (LTMLE), a plug-in estimator with double robust and local efficiency properties. We describe strategies for dealing with high-dimensional potential drinking patterns and practical positivity violations due to a long follow-up time, including modifying the effect of interest by removing sparsely observed drinking patterns from the loss function and applying longitudinal modified treatment policies to represent the effect of discouraging drinking.
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A meta-analysis of the effect of paper versus digital reading on reading comprehension in health professional education
Fontaine, Guillaume; Zagury-Orly, Ivry; Maheu-Cadotte, Marc-André; Lapierre, Alexandra; Thibodeau-Jarry, Nicolas; De Denus, Simon; Lordkipanidzé, Marie; Dupont, Patrice; Lavoie, Patrick; Université de Montréal. Faculté de médecine; Université de Montréal. Faculté de pharmacie; Université de Montréal. Faculté des sciences infirmières (American Association of Colleges of Pharmacy, 2021-12-29)
Objective. Despite a rise in the use of digital education in health professional education (HPE), little is known about the comparative effectiveness of paper-based reading and its digital alternative on reading comprehension. The objectives of this study were to identify, appraise, and synthesize the evidence regarding the effect of how media is read on reading comprehension in the context of HPE. Methods. Observational, quasi-experimental, and experimental studies published before April 16, 2021, were included if they compared the effectiveness of paper-based vs digital-based reading on reading comprehension among HPE students, trainees, and residents. Random-effects meta-analyses were performed using standardized mean differences. Results. From a pool of 2,208 references, we identified and included 10 controlled studies that had collectively enrolled 817 participants. Meta-analyses revealed a slight but nonsignificant advantage to students reading paper-based HPE texts rather than digital text (standardized mean difference, -0.08; 95% CI -0.28 to 0.12). Subgroup analyses revealed that students reading HPE-related texts had better reading comprehension when reading text on paper rather than digitally (SMD 5 -0.36; 95% CI -0.69 to -0.03). Heterogeneity was low in all analyses. The quality of evidence was low because of risks of bias across studies. Summary. Current evidence suggests little to no difference in students’ comprehension when reading HPE texts on paper vs digitally. However, we observed effects favoring reading paper-based texts when texts relevant to the students’ professional discipline were considered. Rigorous studies are needed to confirm this finding and to evaluate new means of boosting reading comprehension among students in HPE programs.
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Antiplatelet therapy in atherothrombotic diseases : similarities and differences across guidelines
Jourdi, Georges; Marquis-Gravel, Guillaume; Martin, Anne-Céline; Lordkipanidzé, Marie; Godier, Anne; Gaussem, Pascale; Université de Montréal. Faculté de pharmacie (Frontiers media, 2022-04-27)
Antiplatelet therapy, mainly consisting of aspirin and P2Y12 receptor antagonists, is the cornerstone of the pharmacological treatment and prevention of atherothrombotic diseases. Its use, especially in secondary cardiovascular prevention, has significantly improved patient clinical outcomes in the last decades. Primary safety endpoint (i.e., bleeding complications) remain a major drawback of antiplatelet drugs. National and international societies have published and regularly updated guidelines for antiplatelet therapy aiming to provide clinicians with practical recommendations for a better handling of these drugs in various clinical settings. Many recommendations find common ground between international guidelines, but certain strategies vary across the countries, particularly with regard to the choice of molecules, dosage, and treatment duration. In this review, we detail and discuss the main antiplatelet therapy indications in the light of the different published guidelines and the significant number of recently published clinical trials and meta-analyses and highlight the areas that deserve further investigation in order to improve antiplatelet therapy in patients with atherothrombotic diseases.
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Assessing cardiometabolic parameter monitoring in inpatients taking a second-generation antipsychotic : the CAMI-SGA study – a crosssectional study
Fontaine, Jennifer; Chin, Evelyn; Provencher, Jean-François; Rainone, Anthony; Wazzan, Dana; Roy, Carmella; Rej, Soham; Lordkipanidzé, Marie; Dagenais-Beaulé, Vincent; Université de Montréal. Faculté de pharmacie (BMJ Publishing Group, 2022)
Objectives This study aims to determine the proportion of initial cardiometabolic assessment and its predicting factors in adults with schizophrenia, bipolar disorder or other related diagnoses for whom a second-generation antipsychotic was prescribed in the hospital setting. Design Cross-sectional study. Setting The psychiatry unit of a Canadian tertiary care teaching hospital in Montreal, Canada. Participants 402 patients with aforementioned disorders who initiated, restarted or switched to one of the following antipsychotics: clozapine, olanzapine, risperidone, paliperidone or quetiapine, between 2013 and 2016. Primary outcome measures We assessed the proportion of cardiometabolic parameters monitored. Secondary outcome measures We identified predictors that influence the monitoring of cardiometabolic parameters and we assessed the proportion of adequate interventions following the screening of uncontrolled blood pressure and fasting glucose or glycated haemoglobin (HbA1c) results. Results Only 37.3% of patients received monitoring for at least three cardiometabolic parameters. Blood pressure was assessed in 99.8% of patients; lipid profile in 24.4%; fasting glucose or HbA1c in 33.3% and weight or body mass index in 97.8% of patients while waist circumference was assessed in 4.5% of patients. For patients with abnormal blood pressure and glycaemic values, 42.3% and 41.2% subsequent interventions were done, respectively. The study highlighted the psychiatric diagnosis (substance induced disorder OR 0.06 95% CI 0.00 to 0.44), the presence of a court-ordered treatment (OR 0.79 95% CI 0.35 to 1.79) and the treating psychiatrist (up to OR 34.0 95% CI 16.2 to 140.7) as predictors of cardiometabolic monitoring. Conclusions This study reports suboptimal baseline cardiometabolic monitoring of patients taking an antipsychotic in a Canadian hospital. Optimising collaboration within a multidisciplinary team may increase cardiometabolic monitoring.
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Clinical correlates identify ProBDNF and thrombo-inflammatory markers as key predictors of circulating p75NTR extracellular domain levels in older adults
Fleury, Samuel; Schnitzer, Mireille; Ledoux-Hutchinson, Lawrence; Boukhatem, Imane; Bélanger, Jean-Christophe; Welman, Mélanie; Busseuil, David; Tardif, Jean-Claude; D’Antono, Bianca; Lordkipanidzé, Marie; Université de Montréal. Faculté des arts et des sciences. Département de psychologie; Université de Montréal. Faculté de médecine; Université de Montréal. Faculté de pharmacie (Frontiers Media, 2022-02-21)
The p75NTR receptor binds all neurotrophins and is mostly known for its role in neuronal survival and apoptosis. Recently, the extracellular domain (ECD) of p75NTR has been reported in plasma, its levels being dysregulated in numerous neurological diseases. However, the factors associated with p75NTR ECD levels remain unknown. We investigated clinical correlates of plasma p75NTR ECD levels in older adults without clinically manifested neurological disorders. Circulating p75NTR levels were measured by enzyme-linked immunosorbent assay in plasma obtained from participants in the BEL-AGE cohort (n = 1,280). Determinants of plasma p75NTR ECD levels were explored using linear and non-linear statistical models. Plasma p75NTR ECD levels were higher in male participants; were positively correlated with circulating concentrations of pro-brain-derived neurotrophic factor, and inflammatory markers interleukin-6 and CD40 Ligand; and were negatively correlated with the platelet activation marker P-selectin. While most individuals had p75NTR levels ranging from 43 to 358 pg/ml, high p75NTR levels reaching up to 9,000 pg/ml were detectable in a subgroup representing 15% of the individuals studied. In this cohort of older adults without clinically manifested neurological disorders, there was no association between plasma p75NTR ECD levels and cognitive performance, as assessed by the Montreal Cognitive Assessment score. The physiological relevance of high p75NTR ECD levels in plasma warrants further investigation. Further research assessing the source of circulating p75NTR is needed for a deeper understanding of the direction of effect, and to investigate whether high p75NTR ECD levels are predictive biomarkers or consequences of neuropathology.

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