Systematic review of hematopoietic stem cell gene therapy approach in thalassemia: Comparative analysis in animal models.

Hematopoietic stem cell (HSC) gene therapy has shown potential as a therapeutic approach for thalassemia in recent years. However, a comparison of the varying gene therapy methods of HSC gene therapy in thalassemia has never been reviewed. This study aims to evaluate the utilization of HSC gene therapy approaches in animal models of thalassemia. A systematic review was conducted in five databases: PubMed, EBSCOHost, Science Direct, SCOPUS, and Proquest using a combination of the terms hematopoietic stem cell or hematopoietic stem cell or HSC, thalassemia, genetic therapy or gene therapy and animal model. Only journals published in English between 2008 and 2023 were included. This literature included six studies analyzing the use of HSC gene therapy in thalassemic mice models. The three outcomes being assessed in this review were globin levels, hematological parameters, and red blood cell (RBC) phenotypes. Gene therapy approaches for thalassemia using HSC showed significant improvement in ß-globin levels and RBC phenotypes. Phenotypic improvements were also observed. These outcomes indicate good efficacy in gene therapy for thalassemia in mice models. Furthermore, more studies assessing the efficacy of HSC gene therapy in the human model should be done in future studies.

Expectation and Needs of Medical Students Towards the Implementation of Virtual Simulation in Learning Rational Use of Medicine.

Introduction: The irrational use of medicines remains prevalent globally despite education efforts, leading to decreased treatment quality and increased healthcare costs. With the rise of online learning during the COVID-19 pandemic, virtual simulation offers a promising solution to enhance the teaching of rational medicine use among medical students. This study aimed to investigate medical students' perspectives and needs regarding the implementation of virtual simulation in learning the rational use of medicines. Methods: This study, conducted at Universitas Indonesia from August 2022 to September 2023, used a mixed-method approach to assess the needs for developing virtual simulation in education of rational medicine use. A validated questionnaire with 14 closed-ended and 14 open-ended questions was completed by 281 medical students. The quantitative data were analysed descriptively, using SPSS v16, while thematic analysis was applied to open-ended responses. Results: Students perceived virtual simulations to be the most effective tool for distance learning and suggested features like case scenarios, realistic representation, a good user interface, and user-friendly navigation. The majority preferred a 10-20-minute duration for virtual simulations. Additionally, 52.3% had no prior knowledge of the rational use of medicines, but acknowledged its importance. Virtual simulations could be used to explain the concept, management, and implementation of the rational use of medicines. Conclusion: Virtual simulation should be implemented in distance learning on rational medicine use to increase students' motivation, understanding, retention, interactivity, and focus. The findings might be utilized by medical educators to tailor virtual simulation design to meet medical students' needs and expectations.

Lack of a relationship between the serum concentration of aminoglycosides and ototoxicity in neonates.

INTRODUCTION: Gentamicin and the other aminoglycosides are toxic antibiotics, but they are urgently needed to treat newborns with neonatal sepsis. Aminoglycosides are well known for their nephrotoxicity and ototoxicity. The aminoglycoside dosage currently applied in Indonesia is derived from studies done in Caucasian populations. The safety and efficacy of this dosage regimen, however, has never been evaluated to date. The pharmacokinetic profile of drugs may vary between populations and this may be influenced by genetic factors, lifestyle, drug interactions, etc. The detection of aminoglycoside toxicity in newborns is usually problematic. The present study aims to know the proportion of ototoxicity in newborns in the Cipto Mangunkusumo Hospital treated with gentamicin or amikacin in relation to their trough serum concentration. METHODS: The serum level of gentamicin and amikacin were quantified using Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS), and is assumed to be safe if the trough serum concentrations are < 2 mcg/ml and effective if it is between 5 - 12 mcg/ml. For amikacin the desired trough serum concentrations are < 10 mcg/ml and the peak is between 20 - 30 mcg/ml. The hearing function was assessed by Distortion Product Otoacoustic Emission (DPOAE) instrument. This study is registered with the www.clinicaltrials.gov NCT01624324. CONCLUSION: Our study indicated that there was no relationship between aminoglycosides serum trough concentration and ototoxicity in neonates with neonatal sepsis.

Comparison Between Self-Deliberate Practice and Directed Learning Training Methods for Basic Life Support Knowledge and High-Quality Cardiopulmonary Resuscitation Skill Retention in Second-Year Medical Students 3 and 6 Months After Training.

Background: Cardiopulmonary resuscitation (CPR) requires well-trained medical personnel. Multiple learning methods can be done for CPR skills training. This study aimed to compare self-deliberate practice (SDP) method and directed learning (DL) method to improve basic life support (BLS) knowledge and CPR skill performance in medical students. Methods: This is an experimental, single-blind, randomized controlled trial study of 40 medical students from February to July 2019. Forty subjects were randomly assigned into SDP and DL groups through a voluntary sampling method. Both groups attended a 1-day course and then practiced once a month for 3 months. The DL group had practice sessions with assigned tutors, while the SDP group had to practice by themselves. Examination of BLS knowledge and CPR performance quality (compression depth, rate, and performance score) was collected before and after course lecture, after a skills training, 3 and 6 months after training. Results: Subject characteristics of both groups were comparable. Significant knowledge and skill improvement were found in the DL group and the SDP group when compared to their knowledge and skill before training. There were no significant differences between both groups in BLS knowledge and CPR performance quality in all examination periods. Conclusion: Both SDP and DL teaching methods show significant improvement and excellent retention in BLS knowledge and high-quality CPR performance. These two learning methods are both feasible and bring positive results for students. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01746-7.

Immunogenicity and Efficacy of Insulin Glargine Biosimilar Ezelin versus Originator Insulin Glargine in Patients with Type 2 Diabetes.

PURPOSE: To compare the immunogenicity and efficacy of insulin glargine biosimilar Ezelin (EZL) versus originator insulin glargine Lantus (LAN) as a reference basal insulin in patients with type 2 diabetes (T2D). PATIENTS AND METHODS: This was a randomized, multicenter, open-label, 24-week study in insulin-naïve patients with T2D, with HbA1c of >7.0%. We randomly assigned 133 eligible patients to receive either EZL or LAN. Baseline characteristics, including insulin autoantibody (IAA), zinc transporter 8 (ZnT8) antibody, HbA1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), AST, ALT, BUN, eGFR, and oral antidiabetic drugs, were obtained before starting insulin treatment. After starting treatment, insulin dose was titrated to achieve FPG target along with oral antidiabetic drugs. Patients were given home glucometer and assisted to record plasma glucose measurement and adverse event (AE). Every month, patients came to the diabetes clinic and performed a regular physical examination and intensifying treatment if needed. Out of the 133 randomized patients, only 122 completed the study and can be examined for their IAA and ZnT8 after 6 months of treatment. The study was registered in clinicaltrials.gov, NCT03352674. RESULTS: There is a similar proportion of patients with changes of IAA from baseline: 1 out of 58 (1.7%) patients receiving EZL versus 1 out of 64 (1.6%) patients receiving LAN (p = 1.000). One patient in the EZL group (1.7%) versus none in the LAN group experienced a change of ZnT8 antibody from baseline. Similar glucose control in EZL versus LAN was determined by the change in HbA1c, FPG, and 2hPPG (-2.0%, -67.46 mg/dL, and -76.51 mg/dL in the EZL group versus -1.7%, -58.11 mg/dL, and -70.03 mg/dL in the LAN group). There were six events of documented hypoglycemia in the EZL group versus five events in the LAN group. No patients experienced diabetic ketoacidosis during the study. CONCLUSION: Overall, insulin glargine biosimilar EZL and originator insulin glargine LAN have shown a similar immunogenicity profile, as well as efficacy in providing glucose control and safety findings in T2D populations.