Exploring the interest of medical students in global health in South Korea: Does taking a global health course matter?

BACKGROUND: Prioritizing global health is important for positive health outcomes. Doctors play a pivotal role in addressing health issues that they need to recognize the importance of global health practice. However, medical education in global health is still in its early stages in many countries, including South Korea. METHODS: This study is a quantitative cross-sectional study. Medical students were recruited from all 40 Korean medical schools and data collection was conducted in 2021. Stratified proportional quota sampling was employed as the sampling method. The study examined medical students' interest in global health as the dependent variable. Independent variables included whether individuals had taken global health courses as part of their medical curriculum, while covariates included student background and institutional factors. Logistic regression was used to determine if taking a global health class was associated with global health interests. RESULTS: The study included 2450 participants and almost 32% of medical students (n = 781) were interested in global health. Taking global health classes in school was associated with a higher likelihood of developing an interest in global health (OR: 1.29, 95% CI: 1.00-1.67). The likelihood of being interested in global health decreased across the academic year (OR: 0.70, 95% CI: 0.53-0.94). Individuals in graduate entry programs were associated with an interest in global health (OR: 1.32, 95% CI: 1.01-1.72). CONCLUSION: This study provides the first comprehensive nationwide assessment of medical students' perspectives on global health education in South Korea. The findings underscore the importance of early and sustained exposure to global health topics in medical education in fostering interest in global health. These results can serve as valuable evidence for medical educators seeking to integrate global health education into their curricula.

Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301.

PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

Comparative pharmacokinetics of two formulations of 2.5-mg rivaroxaban in healthy Korean subjects.

OBJECTIVE: Rivaroxaban is a direct factor Xa inhibitor used for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the pharmacokinetic profiles of two rivaroxaban formulations after a single dose of rivaroxaban (2.5-mg tablet) in healthy Korean subjects. MATERIALS AND METHODS: This study was a randomized, open-label, single-dose, two-period, crossover study that included 34 healthy adult subjects under fasting conditions. The test drug (Yuhan rivaroxaban tablet) or reference drug (Xarelto tablet) was administered in each period. Serial blood samples were collected up to 36 hours post-dose. Plasma concentrations were measured by LC-MS/MS. Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable concentration (AUCt), were determined by non-compartmental analysis. The 90% confidence intervals (CIs) for the ratio of the geometric means of Cmax and AUCt for the test drug/reference drug were calculated to evaluate pharmacokinetic equivalence. RESULTS: A total of 28 subjects were included in the pharmacokinetic analysis. The geometric mean ratios (90% CI) of the test drug/reference drug for rivaroxaban were 1.0140 (0.9794 - 1.0499) for AUCt and 0.9350 (0.8797 - 0.9939) for Cmax. All adverse events (AEs) were mild, and there was no significant difference in the incidence of AEs between the formulations. CONCLUSION: The pharmacokinetic parameters of rivaroxaban were compared between the test and reference drug, and both formulations were bioequivalent. The newly developed rivaroxaban tablet is safe and well tolerated as the reference drug (ClinicalTrials.gov identifiers: NCT05418803).

Effects of food and race on the pharmacokinetics of lazertinib in healthy subjects and patients with EGFR mutation-positive advanced non-small cell lung cancer.

OBJECTIVES: Lazertinib is a potent, irreversible, brain-penetrant, mutant-selective, and wild type-sparing third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for advanced non-small cell lung cancer (NSCLC). The study aimed to evaluate the effects of food and race on the pharmacokinetics (PK) of lazertinib from a healthy volunteer trial and PK data from NSCLC patients with EGFR mutation. MATERIALS AND METHODS: An open-label, single-dose, two-period, single-sequence crossover study was conducted in healthy subjects with two race groups (non-Asian and Asian). Subjects orally received a single dose of lazertinib 240 mg in fasted and fed state (high-fat meal) in each period separated by a 21-day washout. An open-label, multicenter, phase 1/2 study was conducted in Asian and non-Asian patients with NSCLC. Patients were given oral lazertinib 20-320 mg once daily in fasted state continuously in 21-day cycles. PK parameters were evaluated using non-compartmental analysis. RESULTS: A total of 24 healthy subjects (12 non-Asians and 12 Asians) and 52 NSCLC patients (22 non-Asians and 30 Asians) were evaluated. The change in the overall systemic exposure of lazertinib at fed state was less than 15%. Non-Asians showed 58-76% of the systemic exposure than Asians in healthy subjects. In contrast, there were no significant differences in systemic exposure by race both after single and multiple doses among NSCLC patients. CONCLUSION: Lazertinib can be taken with or without food considering the comparable systemic exposures related to food. Although effect of race was not consistent across studies, there was no evidence for dose adjustment based on race.

Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function.

A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.73m2 (Cohort A) and 30-60 mL/min/1.73m2 (Cohort B). Eight subjects in Cohort A received a YHD1119 75 mg tablet (Y75T) and a YHD1119 150 mg tablet (Y150T) in each period, and eight subjects in Cohort B received a Y75T. Non-compartment analysis and population pharmacokinetic analysis using a one-compartment model with first-order elimination and first-order absorption with lag time were performed. Sixteen subjects completed the study. The geometric mean ratio (GMR) (90% confidence intervals [CI]) for maximum concentration (Cmax), and area under the concentration-time profile from 0 to the last measurable time (AUClast) after Y75T of Cohort B to those of Y75T of Cohort A were 1.2273 (1.0245-1.4701), and 2.4146 (1.8142-3.2138), respectively. The GMR (90% CI) for Cmax, and AUClast after Y75T of Cohort B to those of Y150T of Cohort A were 0.6476 (0.5229-0.8021), and 1.1471 (0.8418-1.5632), respectively. Simulated steady-steady pregabalin concentrations after once-daily Y75T dosing in subjects with eGFR 45 mL/min/1.73 m2 were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m2. The total pregabalin exposure of Y75T in patients with moderate renal impairment was comparable with that of Y150T in subjects with near-normal renal function. Trial Registration: ClinicalTrials.gov Identifier: NCT05012436.

Pharmacokinetics of a New, Once-Daily, Sustained-release Pregabalin Tablet in Healthy Male Volunteers.

PURPOSE: A new sustained-release (SR) pregabalin formulation (YHD1119) designed for once-daily dosing has recently been developed to improve patient adherence. This study aimed to compare the pharmacokinetics of pregabalin SR and immediate-release (IR) formulations after multiple oral doses and to assess the effect of food on the pharmacokinetic profile of the pregabalin SR formulation after a single dose in healthy individuals. METHODS: Two clinical trials were conducted: a randomized, open-label, multiple-dose, 2-treatment, 2-period crossover study to evaluate the steady-state pharmacokinetic properties of SR treatment (pregabalin SR 300 mg once daily for 3 days) and IR treatment (pregabalin IR 150 mg twice daily for 3 days) under fed conditions and a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the effect of food intake on the pharmacokinetic properties of the pregabalin SR formulation. Plasma concentrations of pregabalin were measured using LC-MS/MS. The AUC and Cmax for pregabalin were calculated using noncompartmental method and compared between treatments in each study. FINDINGS: Thirty-one individuals in the bioequivalence study and 23 in the food effect study completed the pharmacokinetic sampling. The geometric mean ratios of Cmax,ss and AUC0-τ between the SR and IR formulations were 1.1642 (90% CI, 1.1043-1.2272) and 0.9704 (90% CI, 0.9372-1.0047), respectively. The geometric mean ratios of Cmax and AUC0-last between the SR formulation in the fed state and in the fasted state were 1.6514 (90% CI, 1.3820-1.9732) and 1.7899 (90%CI, 1.4499-2.2097), respectively. IMPLICATIONS: The bioavailability of the pregabalin SR 300 mg formulation is increased if taken with a high-fat meal. Once-daily pregabalin SR 300 mg is bioequivalent to twice-daily pregabalin IR 150 mg under fed conditions at steady state. The pregabalin SR formulation is expected to improve patient adherence. ClinicalTrials.gov identifiers: NCT02783183 (bioequivalence study) and NCT03191136 (food effect study).

A rare case of intraparenchymal subependymoma in a child.

Subependymoma is a slow-growing, exophytic, intraventricular glial neoplasm that commonly arises in the ventricular system. However, a report found that the frequency of intracerebral subependymoma was 0.4% in 1000 routine autopsies. To the best of our knowledge, only seven cases of intracerebral subependymoma have been reported. We report a rare case of intracerebral subependymoma in a child. An 11-year-old girl with generalized tonic-clonic seizures visited the emergency room and had an intraparenchymal tumor on the left frontal lobe on magnetic resonance imaging (MRI). Craniotomy with gross total removal was performed without any perioperative morbidities. The tumor was finally histopathologically diagnosed as a subependymoma.

Pharmacodynamic evaluation of YH4808 for Helicobacter pylori eradication in healthy subjects.

YH4808 is a novel selective potassium-competitive acid blocker demonstrated to be safe and to have inhibitory effects against gastric acid secretion in previous studies. A randomized, open-label, multiple-dose, 3-treatment, 1-period, parallel design study was conducted to compare the Helicobacter pylori eradication rates and acid suppression capacities of three regimens in 60 healthy subjects with H. pylori-positive, and the potential of YH4808 to replace proton-pump inhibitors (PPIs) in standard regimens for H. pylori eradication. Group 1 received YH4808, amoxicillin, and clarithromycin as a novel triple regimen, while Group 2 received YH4808 and amoxicillin only, and Group 3 received esomeprazole, amoxicillin, and clarithromycin, as the standard triple regimen. H. pylori eradication rates were 85.0% for Group 1, 25.0% for Group 2, and 83.3% for Group 3. Relative response rate between Group 1 and 3 was 1.02 (0.50-2.07; 95% CI, χ2 test p = 0.8881). Furthermore, the novel triple regimen, YH4808, amoxicillin, and clarithromycin, stably inhibited acid secretion and maintained a gastric pH greater than 4 or 5 for 24 hours, which was comparable to the pH range in the standard triple regimen. However, the onset times of the YH4808 regimens were earlier than that for the regimens using esomeprazole. There were no differences in the incidences or severity of adverse events among the three groups. Overall, the novel triple regimen was safe and well-tolerated. YH4808 could replace PPIs in standard triple regimens used for H. pylori eradication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01921647.

Evaluation of pharmacokinetic interactions between amoxicillin, clarithromycin, and the potassium-competitive acid blocker YH4808 in healthy subjects.

YH4808 is a novel potassium-competitive acid blocker that was developed as a therapeutic agent for gastric acid-related diseases; it may replace proton pump inhibitors, which are widely used in combination with amoxicillin and clarithromycin for Helicobacter pylori eradication. We compared the pharmacokinetic (PK) profiles and safety of amoxicillin, clarithromycin, and YH4808 used as monotherapies or in combination for evaluating potential drug interactions. An open-label, randomized, single-dose, Latin-square (4 × 4) crossover study was conducted in 32 healthy Korean volunteers. Subjects were randomly assigned to one of the 4 treatment sequences that consisted of 4 periods separated by 21-day washout intervals. PK parameters of YH4808, amoxicillin and clarithromycin administered in combination were compared with those of the respective monotherapies. The geometric mean ratios of the maximum concentration (Cmax) and the area under the time-concentration curve from time zero to time of the last quantifiable concentration (AUClast) of YH4808 increased during the triple therapy by 48.6% and 29.1%, respectively. Similarly, the Cmax and AUClast of M3 (active metabolite of YH4808) increased by 23.3% and 16.0%, respectively. The Cmax and AUClast of clarithromycin increased by 27.4% and 30.5%, and those of 14-hydroxyclarithromycin were increased by 23.1% and 32.4%, respectively. The corresponding amoxicillin values decreased during the triple therapy by 21.5% and 15.6%, respectively. There was no clinically significant change in safety assessment related to either monotherapies or triple therapy. In conclusion, amoxicillin, clarithromycin and YH4808 administered as triple therapy did not exhibit significant PK interactions and were not associated with safety issues. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01921647.

Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects.

PURPOSE: Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers. PATIENTS AND METHODS: An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration versus time curve over dosing interval (AUCτ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax,ss and AUCτ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions. RESULTS: Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Cmax,ss and AUCτ,ss, were 0.9829 (0.8334-1.1590) and 1.0003 (0.9342-1.0710) for telmisartan; 0.9908 (0.9602-1.0223) and 1.0081 (0.9758-1.0413) for amlodipine; and 2.2762 (2.0113-2.5758) and 1.3261 (1.2385-1.4198) for rosuvastatin, respectively. CONCLUSION: The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.

The effects of perioperative intravenous fluid administration strategy on renal outcomes in patients undergoing cardiovascular surgery: An observational study.

We assessed whether perioperative fluid management with balanced solutions and a limited volume of hydroxyethyl starch (renal-protective fluid management [RPF] strategy) could improve renal outcomes after cardiovascular surgery.For this retrospective observational study, we evaluated 2613 patients who underwent cardiovascular surgery from January 1, 2010 to December 31, 2013. The control group were given intravenous fluids with saline-based solutions and unlimited volumes of hydroxyethyl starch solutions and the RPF group were given intravenous fluids with RPF. The primary outcome was the incidence of acute kidney injury (AKI) and chronic dialysis within 12 months after cardiovascular surgery. Multivariable regression and propensity analyses were performed to evaluate the association between perioperative fluid management strategy and postoperative renal outcomes.Postoperative AKI and chronic dialysis occurred in 213 (21.2%) and 5 (0.5%) patients in the RPF group compared with 696 (43.2%) and 38 (2.4%) patients in the control group, respectively. After adjustment, the RPF group was linked to a decreased risk of postoperative AKI, severe AKI, persistent AKI, use of renal replacement therapy, chronic kidney disease, chronic dialysis, and a shorter postoperative extubation time and intensive care unit, and hospital stay duration.The perioperative fluid management strategy with balanced solutions and a limited volume of hydroxyethyl starch was related to improved acute and 1-year renal and clinical outcomes after cardiovascular surgery. These findings indicate the need for further definitive clinical trials on perioperative fluid management strategy.

Inhibitory mechanism of Korean Red Ginseng on GM-CSF expression in UVB-irradiated keratinocytes.

BACKGROUND: UV-irradiated keratinocytes secrete various proinflammatory cytokines. UV-induced skin damage is mediated by growth factors and proinflammatory cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF). In a previous study, we found that the saponin of Korean Red Ginseng (SKRG) decreased the expression of GM-CSF in UVB-irradiated SP-1 keratinocytes. In this study, we attempted to find the inhibitory mechanism of SKRG on UVB-induced GM-CSF expression in SP-1 keratinocytes. METHODS: We investigated the inhibitory mechanism of SKRG and ginsenosides from Panax ginseng on UVB-induced GM-CSF expression in SP-1 keratinocytes. RESULTS: Treatment with SKRG decreased the expression of GM-CSF mRNA and protein induced by irradiation of UVB in SP-1 keratinocytes. The phosphorylation of ERK was induced by UVB at 10 min, and decreased with SKRG treatment in SP-1 keratinocytes. In addition, treatment with SKRG inhibited the UVB-induced phosphorylation of epidermal growth factor receptor (EGFR), which is known to be an upstream signal of ERK. From these results, we found that the inhibition of GM-CSF expression by SKRG was derived from the decreased phosphorylation of EGFR. To identify the specific compound composing SKRG, we tested fifteen kinds of ginsenosides. Among these compounds, ginsenoside-Rh3 decreased the expression of GM-CSF protein and mRNA in SP-1 keratinocytes. CONCLUSION: Taken together, we found that treatment with SKRG decreased the phosphorylation of EGFR and ERK in UVB-irradiated SP-1 keratinocytes and subsequently inhibited the expression of GM-CSF. Furthermore, we identified ginsenoside-Rh3 as the active saponin in Korean Red Ginseng.

Sunlight-induced self-healing of a microcapsule-type protective coating.

Photopolymerization behavior of a methacryloxypropyl-terminated polydimethylsiloxane (MAT-PDMS) healing agent was investigated in the presence of benzoin isobutyl ether (BIE) photoinitiator by Fourier transform infrared (FT-IR) spectroscopy. MAT-PDMS and BIE were microencapsulated with urea-formaldehyde polymer. The surface and shell morphology of the microcapsules was investigated by scanning electron microscopy (SEM). Mean diameter and size distribution of the microcapsules could be controlled by agitation rate. A coating matrix formulation was prepared by sol-gel reaction of tetraethyl orthosilicate (TEOS) in the presence of a polysiloxane and by subsequent addition of an adhesion promoter. The formulation and microcapsules were mixed to give a self-healing coating formulation, which was then sprayed to surface of cellulose-fiber-reinforced-cement (CRC) board or mortar. Contact angle measurements showed that both the polymerized MAT-PDMS and the prepared coating matrix are hydrophobic, and the coating matrix has good wettability with MAT-PDMS. It was confirmed by optical microscopy and SEM that, when the self-healing coating is damaged, the healing agent is released from ruptured microcapsules and fills the damaged region. The self-healing coating was evaluated as protective coating for mortar, and it was demonstrated by water permeability and chloride ion penetration tests that our system has sunlight-induced self-healing capability. Our self-healing coating is the first example of capsule-type photoinduced self-healing system, and offers the advantages of catalyst-free, environmentally friendly, inexpensive, practical healing.