Université de Montréal

In sub-Saharan African countries like Côte d'Ivoire, most individuals with Type 2 diabetes mellitus (T2DM) are undiagnosed, and therefore at risk of experiencing late T2DM diagnosis. Within this region, little is known about late T2DM diagnosis, which is defined as the onset of complications at, or around the time of, laboratory diagnosis. Our objective was to assess the prevalence of late T2DM diagnosis in Abidjan (Côte d'Ivoire) and identify biological and social factors associated with late T2DM diagnosis. A retrospective chart review was carried out between January and May 2022 using patient records in four diabetes centres of Abidjan. Late diagnosis was defined as the onset of at least one T2DM complication within two years following T2DM laboratory diagnosis. Descriptive and multiple correspondence analyses were conducted. Patients (n = 217) had a mean age of 49.0 ± 11.4 years at T2DM laboratory diagnosis, and about half were female (male-female ratio: 0.9). One quarter (25.3%) of patients with T2DM experienced late diagnosis. Most (72.7%) complications observed were chronic. Late diagnosis was associated with older age (≥ 50 years), residence in lower-income municipalities of Abidjan, hypertension, and no family history of T2DM. Age, living area, and family history were significantly associated with early and late T2DM diagnosis in the multiple correspondence analysis. To reduce late T2DM diagnosis and prevent its complications, screening strategies in Côte d'Ivoire could consider prioritizing older adults, adults living in lower-income municipalities of Abidjan, and those without family history of T2DM. The online version contains supplementary material available at 10.1007/s40200-026-01879-7.

Mitochondrial electron transport flavoprotein (ETF) insufficiency causes metabolic diseases known as a multiple acyl-CoA dehydrogenase deficiency (MADD). In contrast to muscle, ETFDH is a non-essential gene in acute lymphoblastic leukemia NALM6 cells, and its expression is reduced across human cancers. In various human cancer cell lines and mouse models, ETF insufficiency caused by decreased ETFDH expression limits flexibility of OXPHOS fuel utilisation but paradoxically increases bioenergetics and accelerates neoplastic growth via activation of the mTORC1/BCL-6/4E-BP1 axis. Collectively, these findings reveal that while ETF insufficiency is rare and has detrimental effects in non-malignant tissues, it is common in neoplasia, where ETFDH downregulation leads to bioenergetic and signaling reprogramming that accelerates neoplastic growth.

Antiretroviral therapy is critical for preventing perinatal HIV transmission during pregnancy; however, access is shaped by complex structural factors, including access to prenatal care, insurance status and provincial drug-coverage policies. Despite its importance, little is known about how out-of-pocket antiretroviral therapy costs during pregnancy differ within and across Canada. We performed a secondary analysis of Quebec data from the Canadian Perinatal HIV Surveillance Program collected between 2019 and 2023, which included 225 pregnant women and pregnant people living with HIV. Out-of-pocket antiretroviral therapy costs were estimated using insurance information, medication prices, and provincial drug formularies. Additionally, we modelled hypothetical case scenarios to examine how antiretroviral therapy costs during pregnancy differed based on income level and province of residence. In the Quebec cohort, out-of-pocket antiretroviral therapy costs during pregnancy varied substantially by insurance coverage. Individuals without insurance faced median costs in pregnancy nearly 10 times higher (CAD $9380) than those with public (CAD $934) or private insurance (CAD $1196). Those insured under the Interim Federal Health Program incurred no costs (CAD $0). Simulated scenarios across provinces and territories revealed further disparities, with some jurisdictions providing full public coverage while others required out-of-pocket payments up to CAD $4296. Out-of-pocket costs for antiretroviral therapy during pregnancy remain high and inequitably distributed in Canada, with uninsured individuals facing the greatest burden in Quebec. These findings highlight the need for policy reforms to ensure free and equitable access to antiretroviral therapy during pregnancy, regardless of insurance coverage.

Older adults living with neurocognitive disorders (NCD) face a higher risk of polypharmacy, exposure to potentially inappropriate medications and related adverse events. Pharmacists can help manage these issues and improve the appropriateness of pharmacotherapy. To evaluate the impact of pharmacists' interventions, as members of primary care interprofessional teams, on medication use and patient-reported outcome measures among older adults living with or under investigation for a neurocognitive disorder. The effect of a six-month follow-up by a primary care interprofessional team pharmacist on the number of medications, potentially inappropriate medications (PIMs) and anticholinergic burden for older adults living at home under evaluation for or living with a NCD was assessed through a controlled quasi-experimental study. Eligible older adults were 65 years or older and were enrolled between September 2021 and February 2025. The patient-reported outcomes were the evolution of participants' quality of life, treatment burden and satisfaction with care. The outcomes were evaluated using difference in differences (D-I-D) and their 95% confidence interval (95% CI). Pharmacist interventions significantly reduced the mean anticholinergic burden in the intervention arm (n=177) compared to the control arm (n=128) (D-I-D: -0.29; 95% CI: -0.56 - -0.11). A non-statistically significant trend toward a reduction was also observed for the mean number of PIMs (D-I-D: -0.11; [-0.22; 0.00]). The interventions also improved participants' satisfaction with care (6.97; [0.23; 13.72]). The mean number of medications used, as well as the burden of treatment and quality of life were stable after follow-up. Pharmacist-led interventions in interprofessional primary care settings contributed to the appropriateness of pharmacotherapy and satisfaction of older adults under evaluation for or living with a NCD after a six-month follow-up.

Multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium (S. Typhimurium) poses a growing threat to food safety and animal health, particularly in the swine industry. In this study, we characterized a highly resistant ST strain isolated from a Quebec swine farm using whole-genome sequencing and phenotypic assays. The isolate harbored two plasmids, one of which encoded resistance to seven major antibiotic classes, including β-lactams, aminoglycosides, and sulfonamides, along with multiple virulence factors. To counteract these resistance mechanisms, we developed a nano-enabled antibacterial combination therapy (NeACT) by co-encapsulating amoxicillin (AMOX) and the β-lactamase inhibitor tazobactam into cyclodextrin encapsulated in liposomes (LP-CAT). Physicochemical analysis confirmed optimal particle size, charge, and stability, while checkerboard assays demonstrated strong drug synergism. The LP-CAT formulation drastically restored antimicrobial efficacy, reducing the AMOX minimum inhibitory concentration (MIC) from >2000 µg/mL to ~60 µg/mL. Using porcine intestinal epithelial (IPEC-J2) cells as an intracellular infection model, our study showed the potential of LP-CAT to remove >94% of intracellular bacteria with no cytotoxic effect. The ability of LP-CAT to resolve intestinal infection was further verified in Caenorhabditis elegans (C. elegans) intestinal infection model. These findings establish LP-CAT as a safe and effective strategy to revive antibiotic potency against intracellular MDR pathogens, offering a novel tool for combating antimicrobial resistance in livestock and safeguarding public health.

Hereditary angioedema is a bradykinin-mediated, rare condition characterised by recurrent and potentially life-threatening attacks of subcutaneous and submucosal swelling. Bradykinin B2 receptor antagonism is a proven mechanism for on-demand treatment of attacks, but no evidence exists on its effects when used prophylactically. Deucrictibant is an investigational orally bioavailable bradykinin B2 receptor antagonist. We aimed to evaluate the efficacy, safety, and tolerability of two dose regimens of oral deucrictibant administered as prophylaxis against hereditary angioedema attacks. CHAPTER-1 was a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial conducted in two parts, a double-blind placebo controlled first part and an open-label second part, with only part 1 reported here. Part 1 recruited adults (aged 18-75 years) with hereditary angioedema type 1 or 2 from 37 sites (university hospitals and accredited angioedema centres) across North America, Europe, and Israel. Patients required a documented history of three or more attacks within the last 3 consecutive months before screening or two or more during the screening period (up to 8 weeks) to be eligible. An interactive response technology system randomised eligible patients 1:1:1 to receive oral deucrictibant 20 mg daily, 40 mg daily, or matching placebo for 12 weeks. Randomisation to treatment groups was stratified by the baseline attack rate. Patients, investigators, site personnel, and the sponsor were blinded to treatment assignment. Masking was achieved with identically appearing deucrictibant and placebo capsules. The primary endpoint was the time-normalised number of investigator-confirmed attacks per 4 weeks (monthly attack rate) from weeks 1 to 12 and was assessed using the intention-to-treat set. The endpoint was analysed by comparing each deucrictibant group with the placebo group using a Poisson generalised linear model with a log link function and Pearson's χ2 scaling of SEs to account for potential dispersion. The safety analysis set included all patients who were randomly assigned and who received one or more doses of study drug (deucrictibant or placebo). CHAPTER-1 is registered with ClinicalTrials.gov (NCT05047185) and is now complete. Between March 9, 2022, and June 19, 2023, 44 patients were screened. Of 34 patients who were randomly assigned, 11 patients received deucrictibant 20 mg, 12 patients received deucrictibant 40 mg, and 11 patients received the placebo, with a median follow-up of 85·0 days (IQR 84·0-86·0). 21 (62%) patients were female, 13 (38%) were male, and 34 (100%) patients were White. The least squares mean monthly attack rate (primary analysis) was 0·40 (95% CI 0·18-0·92) for deucrictibant 20 mg, 0·30 (0·11-0·81) for deucrictibant 40 mg, and 1·93 (1·30-2·88) for placebo; percent reduction in attack rate compared with placebo was 79·2% (95% CI 47·2-91·8) for deucrictibant 20 mg (p=0·0010) and 84·5% (95% CI 53·8-94·8) for deucrictibant 40 mg (p=0·0008). Treatment-related treatment-emergent adverse events were experienced by two (18%) patients receiving deucrictibant 20 mg, one (8%) patient receiving deucrictibant 40 mg, and one (9%) patient receiving the placebo; all were mild in severity (grade 1) and did not require dosing modification of the study drug. There were no serious adverse events or deaths in any treatment group. To the best of our knowledge, this trial provides the first clinical evidence and proof-of-concept for bradykinin B2 receptor antagonism as a therapeutic approach for the prevention of hereditary angioedema attacks and supports further investigation of oral deucrictibant for bradykinin-mediated angioedema. Pharvaris.