Are Mediators of Grief Reactions Better Predictors Than Risk Factors? A Study Testing the Role of Satisfaction With Rituals, Perceived Social Support, and Coping Strategies.

The present study aimed to assess the mediating role of adjustment processes in known risk factors associated with prolonged grief disorder. Data were collected in March-April 2021 through an online survey of 542 Canadian adults bereaved since March 2020. The mediating role of satisfaction with funeral rituals, bereavement support, and coping strategies on grief outcomes was tested using structural equation modeling.

Designing a resilience-based intervention program for children with cancer and their families: a study protocol.

Background: Advances in pediatric oncology have significantly increased survival rates, yet have introduced challenges in managing long-term treatment side effects. This study process introduces an interdisciplinary clinical intervention program rooted in the family resilience framework, aimed at improving well-being across the cancer trajectory for children and their families, especially those in Canadian communities far from specialized oncology centers with limited access to resources.

Methods: Employing an intervention mapping approach, this program collaboratively involves patients, families, professionals, and researchers.

Scoping Review on Transitions in the Context of Pediatric Palliative Care.

Children with complex and chronic conditions receiving palliative care will likely experience many transitions during their life and their treatments. Transition periods for children with life-limiting conditions and their families can be bewildering and highly anxiety-inducing. However, clinical observations seem to point to a more heterogenous care offer, including a lack or discontinuity of services, at the expense of their quality of life.

[End-of-life support experiences at home during the Covid-19 pandemic: Issues and challenges].

Objective The aim of this text is to describe the challenges and issues associated with family caregivers during the experience of caring for a person at the end of life at home, in the context of a pandemic. This support situation, already normally demanding, turned out to be more difficult and complicated than usual due to the many challenges and issues associated, in particular, with the health restrictions imposed at the time. Here, we present an analysis of comments gathered from family caregivers during the pandemic.

Stability of Opened Durvalumab (IMFINZI) Vials. The Beginning of the End of Costly Product Wastage?

Durvalumab is a monoclonal antibody approved for the treatment of lung, urothelial and biliary tract cancers. Durvalumab is supplied in vials as a solution containing no preservatives. Monographs recommend single use of durvalumab vials, and that any leftovers be discarded within 24 h.

Overview of Cardiac Arrhythmias and Treatment Strategies.

Maintenance of normal cardiac rhythm requires coordinated activity of ion channels and transporters that allow well-ordered propagation of electrical impulses across the myocardium. Disruptions in this orderly process provoke cardiac arrhythmias that may be lethal in some patients. Risk of common acquired arrhythmias is increased markedly when structural heart disease caused by myocardial infarction (due to fibrotic scar formation) or left ventricular dysfunction is present.

Tobramycin a Priori Dosing Regimens Based on PopPK Model Simulations in Critically Ill Patients: Are They Transferable?

Background: In recent years, multiple population pharmacokinetic models have been developed for drugs such as tobramycin that need therapeutic drug monitoring. Some of these models have been used to develop a priori dosing regimens for their respective populations. However, these dosing regimens may not apply to other populations.

Homologation of the Alkyl Side Chain of Antimitotic Phenyl 4-(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonate Prodrugs Selectively Targeting CYP1A1-Expressing Breast Cancers Improves Their Stability in Rodent Liver Microsomes.

Phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) are a new family of antimitotic prodrugs bioactivated in breast cancer cells expressing CYP1A1. In this study, we report that the C-labeled prototypical PAIB-SO [C]CEU-818 and its antimitotic counterpart [C]CEU-602 are distributed in whole mouse body and they show a short half-life in mice. To circumvent this limitation, we evaluated the effect of the homologation of the alkyl side chain of the imidazolidin-2-one moiety of PAIB-SOs.

Development and Evaluation of a Height-Based Tobramycin Initial Dosing Nomogram for the Treatment of Adult Cystic Fibrosis Pulmonary Exacerbations.

Tobramycin is widely used to treat pulmonary exacerbations of cystic fibrosis. Height has been previously found to be significantly more predictive of tobramycin pharmacokinetics than body weight. This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing.

Model Re-Estimation: An Alternative for Poor Predictive Performance during External Evaluations? Example of Gentamicin in Critically Ill Patients.

Background: An external evaluation is crucial before clinical applications; however, only a few gentamicin population pharmacokinetic (PopPK) models for critically ill patients included it in the model development. In this study, we aimed to evaluate gentamicin PopPK models developed for critically ill patients.

Methods: The evaluated models were selected following a literature review on aminoglycoside PopPK models for critically ill patients.

Remdesivir (VEKLURY) for Treating COVID-19: Guinea Pig Ex Vivo and In Vivo Cardiac Electrophysiological Effects.

Bradycardia and QTc interval prolongation on the ECG have been reported with remdesivir (Veklury), an antiviral drug recently approved for treating severely ill patients with COVID-19. The objective was to evaluate the effects of remdesivir on cardiac electrophysiology ex vivo and in vivo. Ex vivo: Langendorff retroperfusion experiments were performed on isolated hearts from male Hartley guinea pigs (n = 23, total) exposed to either remdesivir 3, 10, or 30 µmol/L to assess drug-induced prolongation of the monophasic action potential duration measured at 90% repolarization (MAPD 90 ).

Sociographie des ritualités funéraires en temps de pandémie: des rites empêchés aux rites appropriés.

COVID-19 has led to unprecedented health and social measures in several countries, including major restrictions on funeral rituals. These restrictions concerned pre-mortem, peri-mortem and post-mortem rites. Based on a longitudinal study of 955 French-speaking Canadians bereaved of a loved one during the pandemic, this article describes the reality of these impediments.

Methods of Therapeutic Drug Monitoring to Guide Vancomycin Dosing Regimens: Trough Concentration versus Ratio of Area Under the Curve to Minimum Inhibitory Concentration.

Background: The most recent vancomycin monitoring guideline recommends targeting a value for area under the curve (AUC) of 400 to 600 mg*h/L, with an assumed minimum inhibitory concentration (MIC) of 1 mg/L. Few studies have investigated the effect of this method on vancomycin dosing regimens, relative to a target trough concentration of 15 to 20 mg/L.

Objective: To compare vancomycin dosing regimens generated with the 2 monitoring methods.

Aminoglycosides' dosing and monitoring practices in critically ill patients in Quebec hospitals.

Considering the aminoglycosides' characteristics in terms of efficacy and toxicity, multiple dosing recommendations and nomograms have been suggested over several decades. The objective is to describe the dosing and monitoring practices of amikacin, gentamicin, and tobramycin in critically ill patients across health care institutions in the province of Quebec.This survey was developed with multiple-choices and short answers and targeted the lead pharmacist responsible of antimicrobial stewardship in each health care institution.

Women with breast cancer's perceptions of nurse-led telephone-based motivational interviewing consultations to enhance adherence to adjuvant endocrine therapy: a qualitative study.

Background: Daily adjuvant endocrine therapy (AET) for 5 or 10 years is the standard of care for women diagnosed with non-metastatic hormone receptor-positive breast cancer. However, many women experience AET-related issues that may hamper quality of life and adherence. Here, we aimed to describe women's perceptions of motivational interviewing (MI)-guided consultations delivered by a trained nurse navigator over the telephone to enhance AET adherence.

Consideration of height-based tobramycin dosing regimens for the treatment of adult cystic fibrosis pulmonary exacerbations.

Aims: Some population pharmacokinetic models have been developed using height to explain some of the interindividual variability in tobramycin pharmacokinetics in cystic fibrosis patients. However, their predictive performance when extrapolated to other clinical centres is unclear. Therefore, the aim of this study was to externally evaluate the predictability of tobramycin population pharmacokinetic models with an independent dataset and perform simulations using previously recommended height-based dosing regimens.

Aminoglycosides in the Intensive Care Unit: What Is New in Population PK Modeling?

Background: Although aminoglycosides are often used as treatment for Gram-negative infections, optimal dosing regimens remain unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycoside pharmacokinetics in this population.

Objective: This review provides comprehensive data on the pharmacokinetics of aminoglycosides in patients hospitalized in the ICU by summarizing all published PopPK models in ICU patients for amikacin, gentamicin, and tobramycin.

SCN5A-C683R exhibits combined gain-of-function and loss-of-function properties related to adrenaline-triggered ventricular arrhythmia.

New Findings: What is the role of SCN5A-C683R? SCN5A-C683R is a novel variant associated with an uncommon phenotype of adrenaline-triggered ventricular arrhythmia in the absence of a distinct ECG phenotype. What is the main finding and its importance? Functional studies demonstrated that Na 1.5/C683R results in a mixed electrophysiological phenotype with gain-of-function (GOF) and loss-of-function (LOF) properties compared with Na 1.

The Physiopathology of Cardiorenal Syndrome: A Review of the Potential Contributions of Inflammation.

Inter-organ crosstalk plays an essential role in the physiological homeostasis of the heart and other organs, and requires a complex interaction between a host of cellular, molecular, and neural factors. Derangements in these interactions can initiate multi-organ dysfunction. This is the case, for instance, in the heart or kidneys where a pathological alteration in one organ can unfavorably affect function in another distant organ; attention is currently being paid to understanding the physiopathological consequences of kidney dysfunction on cardiac performance that lead to cardiorenal syndrome.

Altered Protein Expression of Cardiac CYP2J and Hepatic CYP2C, CYP4A, and CYP4F in a Mouse Model of Type II Diabetes-A Link in the Onset and Development of Cardiovascular Disease?

Arachidonic acid can be metabolized by cytochrome P450 (CYP450) enzymes in a tissue- and cell-specific manner to generate vasoactive products such as epoxyeicosatrienoic acids (EETs-cardioprotective) and hydroxyeicosatetraenoic acids (HETEs-cardiotoxic). Type II diabetes is a well-recognized risk factor for developing cardiovascular disease. A mouse model of Type II diabetes (C57BLKS/J-) was used.

Fingolimod (Gilenya ) in multiple sclerosis: bradycardia, atrioventricular blocks, and mild effect on the QTc interval. Something to do with the L-type calcium channel?

Cardiac arrhythmias and ECG abnormalities including bradycardia, prolongation of the QT interval, and atrioventricular (AV) conduction blocks have been extensively observed with fingolimod, the first marketed oral drug for treating the relapsing-remitting form of multiple sclerosis. This study was aiming to further elucidate the effects of fingolimod on cardiac electrophysiology at three different levels: (i) in vitro, (ii) ex vivo, and (iii) in vivo. (i) Patch-clamp experiments in whole cell configuration were performed on Ca 1.

Modulation of CYP3a expression and activity in mice models of type 1 and type 2 diabetes.

CYP3A4, the most abundant cytochrome P450 enzyme in the human liver and small intestine, is responsible for the metabolism of about 50% of all marketed drugs. Numerous pathophysiological factors, such as diabetes and obesity, were shown to affect CYP3A activity. Evidences suggest that drug disposition is altered in type 1 (T1D) and type 2 diabetes (T2D).

The guinea-pig expresses functional CYP2C and P-glycoprotein: further validation of its usefulness in drug biotransformation/transport studies.

Background: The guinea-pig is an excellent animal model for studying cardiopulmonary physiology/pharmacology. Interestingly, it also possesses a number of drug-metabolizing enzymes found in humans, such as CYP1A, CYP2D and CYP3A.

Objective: To evaluate the hypothesis that the guinea-pig also expresses a functional CYP2C drug-metabolizing enzyme and the P-glycoprotein (P-gp) drug transporter in various tissues.

Decreased CYP3A expression and activity in guinea pig models of diet-induced metabolic syndrome: is fatty liver infiltration involved?

Background: In humans, CYP3A drug-metabolizing enzyme subfamily is the most important. Numerous pathophysiological factors, such as diabetes and obesity, were shown to affect CYP3A activity. Often considered a precursor state for type II diabetes, metabolic syndrome exerts a modulating role on CYP3A, in our hypothesis.

Iloperidone (Fanapt®), a novel atypical antipsychotic, is a potent HERG blocker and delays cardiac ventricular repolarization at clinically relevant concentration.

QT interval prolongation on the electrocardiogram (ECG) has extensively been reported with iloperidone, a novel antipsychotic drug. The objective of the present study was to evaluate the effects of iloperidone on cardiac ventricular repolarization at three different levels; in vitro, ex vivo and in vivo. (1) In vitro level: whole-cell patch-clamp experiments were performed on HERG-transfected HEK293 cells exposed to iloperidone 0.