Pharmacogenomic screening identifies and repurposes leucovorin and dyclonine as pro-oligodendrogenic compounds in brain repair.

Oligodendrocytes are critical for CNS myelin formation and are involved in preterm-birth brain injury (PBI) and multiple sclerosis (MS), both of which lack effective treatments. We present a pharmacogenomic approach that identifies compounds with potent pro-oligodendrogenic activity, selected through a scoring strategy (OligoScore) based on their modulation of oligodendrogenic and (re)myelination-related transcriptional programs. Through in vitro neural and oligodendrocyte progenitor cell (OPC) cultures, ex vivo cerebellar explants, and in vivo mouse models of PBI and MS, we identify FDA-approved leucovorin and dyclonine as promising candidates.

Publication bias in pharmacogenetics of statin-associated muscle symptoms: A meta-epidemiological study.

Background And Aims: Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.

Olaparib in recurrent isocitrate dehydrogenase mutant high-grade glioma: A phase 2 multicenter study of the POLA Network.

Background: Based on preclinical studies showing that IDH-mutant (IDHm) gliomas could be vulnerable to PARP inhibition we launched a multicenter phase 2 study to test the efficacy of olaparib monotherapy in this population.

Methods: Adults with recurrent IDHm high-grade gliomas (HGGs) after radiotherapy and at least one line of alkylating chemotherapy were enrolled. The primary endpoint was a 6-month progression-free survival rate (PFS-6) according to response assessment in neuro-oncology criteria.

Estimating individualized treatment effects using an individual participant data meta-analysis.

Background: One key aspect of personalized medicine is to identify individuals who benefit from an intervention. Some approaches have been developed to estimate individualized treatment effects (ITE) with a single randomized control trial (RCT) or observational data, but they are often underpowered for the ITE estimation. Using individual participant data meta-analyses (IPD-MA) might solve this problem.

Diabetes, periodontitis, and cardiovascular disease: towards equity in diabetes care.

Type 2 diabetes and its associated cardiovascular risk is an escalating epidemic that represents a significant public health burden due to increased morbidity and mortality, disproportionately affecting disadvantaged communities. Poor glycaemic control exacerbates this burden by increasing retinal, renal, and cardiac damage and raising healthcare costs. This predicament underscores the urgent need for research into cost-effective approaches to preventing diabetes complications.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients presenting sepsis-induced immunosuppression: The GRID randomized controlled trial.

Purpose: Septic shock is associated in some patients with a profound immunosuppression. We hypothesized that GM-CSF would reduce the occurrence of ICU-acquired infections in immunosuppressed septic patients.

Methods: Randomized double-blind trial conducted between 2015 and 2018.

Pharmacokinetic/pharmacodynamic model of a methionine starvation based anti-cancer drug.

A new therapeutic approach against cancer is developed by the firm Erytech. This approach is based on starved cancer cells of an amino acid essential to their growth (the L-methionine). The depletion of plasma methionine level can be induced by an enzyme, the methionine-γ-lyase.

Barriers and Facilitators to the Use of Clinical Decision Support Systems in Primary Care: A Mixed-Methods Systematic Review.

Purpose: To identify and quantify the barriers and facilitators to the use of clinical decision support systems (CDSSs) by primary care professionals (PCPs).

Methods: A mixed-methods systematic review was conducted using a sequential synthesis design. PubMed/MEDLINE, PsycInfo, Embase, CINAHL, and the Cochrane library were searched in July 2021.

Predicted Impacts of Booster, Immunity Decline, Vaccination Strategies, and Non-Pharmaceutical Interventions on COVID-19 Outcomes in France.

The major economic and health consequences of COVID-19 called for various protective measures and mass vaccination campaigns. A previsional model was used to predict the future impacts of various measure combinations on COVID-19 mortality over a 400-day period in France. Calibrated on previous national hospitalization and mortality data, an agent-based epidemiological model was used to predict individual and combined effects of booster doses, vaccination of refractory adults, and vaccination of children, according to infection severity, immunity waning, and graded non-pharmaceutical interventions (NPIs).

Project rebuild the evidence base (REB): A method to interpret randomised clinical trials and their meta-analysis to present solid benefit-risk assessments to patients.

Evidence-based medicine is the cornerstone of shared-decision making in healthcare today. The public deserves clear, transparent and trust-worthy information on drug efficacy. Yet today, many drugs are prescribed and used without solid evidence of efficacy.

SGLT2 inhibitors in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials balancing their risks and benefits.

Aims/hypothesis: Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have been reported. The risk/benefit ratio of SGLT2i remains unquantified.

Do drugs interact together in cardiovascular prevention? A meta-analysis of powerful or factorial randomized controlled trials.

Aim Of The Study: To explore whether preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and hypoglycemic agents) interact together in cardiovascular prevention.

Methods: We searched PubMed®, Web of science™, Embase and Cochrane library for powerful randomized placebo-controlled trials (>1000 patients). We explored whether drug effect on major vascular events changed according to cross-exposure to other drug classes or to cardiovascular risk factors (hypertension or type 2 diabetes), through a meta-analysis of relative odds ratio computed by trial subgroups.

A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy - including photon and proton therapy - for the treatment of radioresistant tumors: the ETOILE trial.

Background: Some cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy.

How do they add up? The interaction between the placebo and treatment effect: A systematic review.

Aim: The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized.

Selected and simplified FDI criteria for assessment of restorations.

Objectives: Assess the quality of dental restorations with simplified FDI criteria and examine its relationships with other general characteristics of restored teeth.

Methods: The study involved 76 dentists from private and hospital practices. Assessments of successes and failures of previous restorations used a simplified rating with FDI criteria 3 to 8, 11, 12, and 14.

Expected Evolution of COVID-19 Epidemic in France for Several Combinations of Vaccination Strategies and Barrier Measures.

The outbreak of the SARS-CoV-2 virus, enhanced by rapid spreads of variants, has caused a major international health crisis, with serious public health and economic consequences. An agent-based model was designed to simulate the evolution of the epidemic in France over 2021 and the first six months of 2022. The study compares the efficiencies of four theoretical vaccination campaigns (over 6, 9, 12, and 18 months), combined with various non-pharmaceutical interventions.

Reappraisal of the efficacy of intensive glycaemic control on microvascular complications in patients with type 2 diabetes: A meta-analysis of randomised control-trials.

Objective: To re-assess the effect of tight glycaemic control on diabetic microvascular complications.

Method: Meta-analysis and trial sequential analyses of randomised trials included in Hemmingsen et al that specifically assessed glycaemic control with a specific HbA level targeted in the intervention group, and compared intensive glycaemic control versus standard glycaemic control.

Results: Seven clinical trials that randomised 28,614 participants with type 2 diabetes (15,269 to intensive control and 13,345 to conventional control), including 3 sub-studies, were included.

Basket clinical trial design for targeted therapies for cancer: a French National Authority for Health statement for health technology assessment.

During the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial.

Needs for re-intervention on restored teeth in adults: a practice-based study.

Objectives: Evaluate the need for re-intervention on dental coronal restorations in adults seen in a network of general dental practitioners (ReCOL).  MATERIALS AND METHODS: This observational, cross-sectional, multicenter study involved 40 practitioners and 400 patients. Coronal restoration failures (needing re-intervention for unsatisfactory outcomes) were assessed with a simplified rating scale of seven criteria from the FDI World Dental Federation.

Place of a new radiological index in predicting pulp exposure before intervention for deep carious lesions.

Background: During interventions for deep caries lesions without severe symptoms, preserving pulpal vitality is important to ensure treatment success, improve organ prognosis, and decrease cost-effectiveness. Current pre-operative radiographs allow visual estimation but not accurate measurement of lesion depth.

Purpose: Investigate the ability of ratio 'remaining/total dentin thickness' (RDT/TDT, as determined on pre-operative radiographs) to predict pulp exposure during excavation.