"Pharmacotrophy": a playful tournament for game- and team-based learning in pharmacology education - assessing its impact on students' performance.

BACKGROUND: At the Faculty of Pharmacy of Paris, we conducted a pharmacology tournament in 2021 and 2022, named "Pharmacotrophy", to offer a game-, team- and competitive-based learning innovation based on fun and challenge. This article aims to (1) provide a detailed overview of the organisation of "Pharmacotrophy," (2) present and compare feedback from both students and teachers, and (3) assess the impact of student participation on their exam marks. METHODS: "Pharmacotrophy" took place in 2021 and 2022 over a two-week period at the beginning of the exam revision phase. It involved a combination of remote matches using the online quiz creation tool Kahoot!® and in-person matches. Teams, consisting of three students from the 4th or 5th year, participated in several selection rounds leading up to the final match. The questions covered various topics from the pharmacology curriculum. Using an anonymous online survey, we collected the feedback from students and teacher regarding the organisation of the tournament and the interest and difficulty of the different type of questions. We retrospectively compared the exam marks of 4th year students who took part in "Pharmacotrophy" (n2021 = 19 and n2022 = 20) with those of the rest of the 4th year (n2021 = 315-320 and n2022 = 279-281), both in the year before "Pharmacotrophy" and just after the tournament. RESULTS: Students highlighted the educational benefits of team-based and game-based learning. This novel approach positively and constructively motivated students to review pharmacology. Additionally, students appreciated the establishment of a trust-based relationship with their teachers. All students had a similar pharmacology level based on their exam results in the year before "Pharmacotrophy." After the tournament, participants had marks 20.1% higher in pharmacology questions compared to non-participants (p = 0.02), while they had comparable overall levels, as evidenced by their final grade averages and marks in non-pharmacology questions. Moreover, participants who advanced further in the competition achieved higher marks in pharmacology questions compared to those who were eliminated early in the tournament. CONCLUSION: The implementation of "Pharmacotrophy" provided students with an enjoyable way to review pharmacology coursework and revived the interest in pharmacology for some. Specifically, participating in "Pharmacotrophy" led to an increase in pharmacology marks for students who were not among the top performers in the class or did not excel in pharmacology in the previous year. This study quantified the pedagogical value of this innovative curriculum in terms of knowledge acquisition.

Valproate, divalproex, valpromide: Are the differences in indications justified?

In many countries, valproate is indicated for epilepsy only, whereas its derivative divalproex (DVP) and valpromide (VPM) are indicated for bipolar disorders only. DVP is composed of sodium valproate and valproic acid (VA) in a 1:1 molar ratio and VPM is a prodrug completely hydrolyzed in the gastric tract to VA. Whatever the drug, the absorbed and active substance is the valproate ion. In this article, we reviewed the potential reasons that might justify these different indications. We performed a literature review of comparative studies of efficacy, pharmacokinetic parameters, side effects and costs for VPA, DVP, and VPM. We found only studies comparing VA with DVP. None of the eight efficacy studies found differences in epilepsy or mood disorders. The ten studies of side effects reported a difference in terms of gastrointestinal effects, but inconsistently. The United States (US) summary of product characteristics and kinetic comparison studies reported bioequivalence between DVP and VA, but a longer Tmax for DVP, likely due to its gastro-resistant galenic form. VPM summary of product characteristics and pharmacokinetic studies revealed a lower bioavailability (80% vs. 100% for VA) and a delayed Tmax. There is an additional cost for using DVP or VPM as compared to VA (respectively +177% and +77% in France). The differences in indications between valproate derivatives do not seem justified. Interchangeability between VA and DVP in bipolar disorders seems possible, at identical dosage. VPM would require a closer dosing schedule and a 20% reduction in dosage when switching to valproate.

Quantitation of 10 antibiotics in plasma: Sulfosalicylic acid combined with 2D-LC-MS/MS is a robust assay for beta-lactam therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) of antibiotics is particularly important in populations with high pharmacokinetic variabilities, such as critically ill patients, leading to unpredictable plasma concentrations and clinical outcomes. Here, we i) describe an original method for the simultaneous quantification of ten antibiotics (cefepime, ceftazidime, ampicillin, piperacillin/tazobactam, cefotaxime, amoxicillin, cloxacillin, oxacillin, linezolid) using 5-sulfosalicylic acid dihydrate (SSA) solution for protein precipitation together with 2D-LC-MS/MS, and ii) evaluate its impact in a one-year retrospective study. The method involved simple dilution with an aqueous mix of deuterated internal standards and plasma protein precipitation with SSA. Twenty microliters of the supernatant was injected into a C8 SPE online cartridge (30 × 2.1 mm) without any evaporation step and back-flushed onto a C18 UHPLC (100 × 2.1 mm) analytical column. Mass spectrometry detection (Xevo TQD) was performed in positive electrospray, in scheduled MRM mode. Overall analytical runtime was 7 min. Due to analytical constraints and the physicochemical properties of the antibiotics, protein precipitation using organic solvents could not be applied. As an alternative, SSA used with 2D-LC offered various advantages: i) lack of dilution resulting in better assay sensitivity, and ii) good chromatography of hydrophilic compounds. Ten microliters of 30% SSA in water eliminated>90% of plasma proteins, including the most abundant high molecular weight proteins at 55 and 72 kDa. The assay was successfully validated according to FDA and EMA guidelines for all the antibiotics, and the coefficients of variation of the quality control (QC) run during sample analysis over one year were below 10%, whatever the QC levels or the antibiotics. The use of 2D-LC combined with SSA precipitation allowed development of a robust, sensitive and rapid quantification assay. Feedback to clinicians was reduced to 24 h, thus allowing rapid dosage adjustment. During one year, 3,304 determinations were performed in our laboratory: 41% were not in the therapeutic range, 58% of which were sub-therapeutic, underlining the importance of early TDM of antibiotics to limit therapeutic failures and the emergence of bacterial resistance.

Arterial Remodelling in Chronic Kidney Disease: Impact of Uraemic Toxins and New Pharmacological Approaches.

Chronic kidney disease (CKD) is a major public health concern that affects around 10 percent of the world's population. The severity of CKD is mainly due to the high prevalence of cardiovascular (CV) complications in this population. The aim of this review is to describe the arterial remodelling associated with CKD, to provide a quick overview of the mechanisms involved and to review the recent pharmacological approaches aimed at improving vascular health in CKD. CKD patients are exposed to metabolic and haemodynamic disorders that may affect the CV system. Large artery functional and geometric abnormalities have been well documented in CKD patients and are associated with an increase in arterial stiffness and a maladaptive remodelling. Uraemic toxins, such as indoxyl sulphate, p-cresyl sulphate, protein carbamylation and advanced glycation products, exert various effects on vascular smooth muscle cell functions. The low-grade inflammation associated with CKD may also affect arterial wall composition and remodelling. It is worth noting that the CV risk for CKD patients remains high despite the pharmacological control of traditional CV risk factors, suggesting the need for innovative therapeutic strategies. An interventional study targeting the NLRP3 inflammasome has provided some interesting preliminary results that need to be confirmed, especially in terms of safety.

Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case detected by exercise testing.

Myoadenylate deaminase deficit (MAD, MIM#615511) is the most common cause of metabolic myopathies with an estimated prevalence of 1-2% in the general population. We report the case of a 39-year-old man suffering from severe skeletal muscle pain that had developed gradually for 4 years. A moderate increase in creatine kinase (CK) was the only biological sign observed. This study takes a closer look at a common but poorly known pathology and highlights the interest of the dynamic metabolic investigations carried out during exercise stress test with a cycle ergometer. Our non-invasive clinical and biological examination, at the interface between physiology and biology, disclosed the total absence of a physiological increase in plasma ammonia evocative of MAD. However, MAD was later confirmed by histochemistry and molecular studies, which revealed the presence of the recurrent homozygous pathogenic variant affecting the adenosine monophosphate deaminase 1 gene (AMPD1) in most patients with MAD.