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University students globally are consistently identified as a vulnerable group for mental distress and suicide. Despite this, students report low engagement in help-seeking behaviours. This series of studies aimed to assess barriers to help-seeking for students and the impact of an intervention that sought to increase support-seeking intentions. In Study 1, 373 undergraduate psychology students completed items related to depression, anxiety, suicidal ideation, stigma, and help-seeking intentions. In Study 2, 133 undergraduate psychology students were randomly allocated into one of three intervention groups (control, infographic, video) and completed measures as used in Study 1. Despite experiencing clinically relevant symptoms and recent suicidal ideation, students in Study 1 tended to report low intentionality to seek help, citing perceptions that their distress was not serious enough or a desire to handle their issues independently. In Study 2, an infographic about different support services increased student’s intentions to access support services and reduced their perception that their issues were not serious enough. Overall, Aotearoa New Zealand students endorsed similar barriers to help-seeking as students in other countries. Importantly, we demonstrated that a simple infographic intervention reduced perceptions regarding these common barriers and may increase students’ knowledge about when to seek help.

Background Amoxicillin/clavulanate is a widely used oral formulation of penicillin combined with a β-lactamase inhibitor. When using amoxicillin/clavulanate in the elderly, the risk of adverse drug reaction may be greater. This study aimed to evaluate the pharmacokinetics (PKs) and safety of multiple-dose amoxicillin/clavulanate administration in healthy elderly subjects and to compare the observed PK profiles with those in healthy younger adults. An open-label, one-sequence, multiple administration study was conducted in 16 healthy elderly subjects. Materials and methods Subjects orally received amoxicillin and clavulanate 750/187.5 twice daily for 9 days. For PK analysis, serial blood samples were collected up to 12 hours after the last administration of amoxicillin/clavulanate. The demographic and PK data of this study were compared to those of healthy young adults from a separate study with a similar design. Safety assessments including clinical laboratory tests, physical examination, vital signs, and adverse event (AE) monitoring were performed throughout the study. Results All AEs were mild, and no serious AEs were reported in this study. The systemic exposure of amoxicillin and clavulanate was ~ 90% and 60% higher, respectively, in the elderly subjects than in the younger subjects. However, the time required to reach maximum concentration at steady state and the elimination half-life were similar in the two age groups. Conclusion Although multiple administration of amoxicillin/clavulanate 750/187.5 mg was safe and well-tolerated, the systemic exposure of amoxicillin and clavulanate was higher in elderly subjects than in younger subjects.

Introduction: Gene expression profiles in human peripheral blood mononuclear cells (PBMCs) may act as a useful tool to better understand obesity. We investigated gene expression levels in PMBCs for possible differences between obese and non-obese subjects (19–55 years) and evaluated correlations between gene expression in PBMCs and clinical obesity indices. Methods: Body weight, BMI, fat amount, fat percentage, waist/hip ratio, leptin, and adiponectin levels were determined in 30 obese and 20 non-obese subjects. Expression levels of 19 genes, which were differentially expressed by clinical obesity indices in the PBMCs of high fat-fed rats, were determined in their PBMCs using real-time PCR. Results: The expression of 9 of 19 previously selected genes was significantly correlated with one or more clinical obesity indices. Both TFEC and CCL2 expression were negatively correlated with BMI, fat amount, fat percentage, waist/hip ratio, and leptin concentration. Similarly, TNFAIP2, VCAN, ASSI, IRF1, and HK3 expression negatively correlated with some clinical obesity indices, such as TNFAIP2 for BMI, fat amount, fat percentage, and waist/hip ratio, VCAN for fat amount, fat percentage, and waist/hip ratio, ASS1 for BMI and fat amount, IRF1 for BMI, fat amount, and fat percentage, and HK3 for fat amount. In contrast, both TNF-α and LPL expression were positively correlated with waist/hip ratio. Conclusion: We identified 9 of 19 genes in human PBMCs that significantly correlated with one or more clinical obesity indices. Because these genes have a mechanistic basis for the development or progression of obesity and its metabolic derangements, they may help to determine possible underlying mechanisms for obesity.

The transition from high school to university is associated with increased alcohol use and harm. Web-based interventions (WBIs) and ecological momentary interventions (EMIs) are two methods that have had some success in reducing alcohol use among university students and may be particularly effective if implemented during the transition to university. The aim of the current study was to investigate the effectiveness of a combined WBI and EMI to reduce alcohol use among incoming university students.Incoming first-year students (n = 783, in 2018 and 2019) were randomized into either a WBI + EMI, WBI-only, or an assessment-only condition. All participants completed online questionnaires before university, after their first and second semester, and reported their alcohol use fortnightly throughout their first year. Those in the WBI + EMI and WBI conditions received online feedback about their drinking (i.e., the WBI) immediately following the pre-university survey. Those in the WBI + EMI were also sent eight EMI messages to their mobile phones during Orientation Week and six EMI messages across the academic year aimed at reducing alcohol harm.There were no significant differences between the conditions in Orientation Week drinking, academic year drinking (both "typical" semester or fortnightly drinking), or alcohol-related harms.A WBI + EMI intervention aimed at the transition to university did not reduce university students' alcohol use. The transition, however, continues to be a period of serious harm where students drink more than any other period.

Purpose Coadministration of lobeglitazone and dapagliflozin is expected to result in a blood glucose–lowering effect, followed by a gradual increase, in clinical usage; however, combining drugs could cause negative interactions. This study aimed to evaluate the effect of the coadministration of lobeglitazone and dapagliflozin on their individual pharmacokinetic properties at steady state in healthy male volunteers in the fasted state. Methods This study consisted of 2 parts, each of which was a randomized, open-labeled, multiple-dose, 2-way crossover study in 20 healthy male volunteers in each part. Blood samples were taken periodically over a 48-h period after dosing to derive total plasma lobeglitazone and dapagliflozin pharmacokinetic properties; safety profile was evaluated throughout the study. Findings When the pharmacokinetic properties of dapagliflozin were evaluated following its administration alone and in combination with lobeglitazone, point estimate and 90% CI of the geometric mean ratio of dapagliflozin AUCτ were entirely within the conventional bioequivalence range of 80%–125%. However, although it was not clinically meaningful, its Css,max was ~8% lower in subjects receiving multiple doses of dapagliflozin and lobeglitazone than that in those administered dapagliflozin alone. The pharmacokinetic properties of lobeglitazone were evaluated following its administration alone and in combination with dapagliflozin. The geometric mean ratios and 90% CIs of the lobeglitazone Css,max and AUCτ were within the conventional bioequivalence range of 80%–125%. Implications Coadministration of lobeglitazone and dapagliflozin had no apparent clinically relevant effects on the pharmacokinetic properties of either drug. Based on these findings, it is anticipated that lobeglitazone and dapagliflozin can be coadministered without dose adjustment. ClinicalTrials.gov identifier: NCT03616392

Seol Ju Moon,1,2Ji-Young Jeon,1 Kyungho Jang,1 Kyung-Sang Yu,2 Yeji Lim,3 Min-Gul Kim1,4–51Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 3Yuhan Research Institute, Yuhan Corporation, Seoul, Republic of Korea; 4Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, Republic of Korea; 5Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of KoreaPurpose: 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 80mg/5mg once daily for 14days with or without one tablet of rosuvastatin 20mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20mg once daily for 14days with or without one tablet of telmisartan/amlodipine 80mg/5mg once daily. Serial blood samples were collected up to 24hrs 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.Keywords: drug–drug interactions, pharmacokinetics, phase I, antihypertensive, statins

A number of studies have reported a positive relationship between levels of national identification and well-being. Although this link is clear, the relationship is likely influenced by a number of other variables. In the current study, we examine two such variables: age and the ease with which people feel they can express their identity in the national context. Participants were drawn from three waves (2008–12) of the biannual New Zealand General Social Survey (NZGSS). The NZGSS consists of a number of questions related to well-being. The current study utilised the questions related to one’s sense of belonging to New Zealand, ease to express one’s identity in New Zealand, and mental health. When controlling for physical health, standard of living, and several demographic control variables, there was a clear relationship between one’s sense of belonging to New Zealand and mental health. Further, this relationship was stronger for older than younger participants. Finally, the ease with which participants felt they could express their identity in New Zealand partially mediated the relationship. Future research should elucidate which specific aspects of their identity people feel is constrained in the national context.A number of studies have reported a positive relationship between levels of national identification and well-being. Although this link is clear, the relationship is likely influenced by a number of other variables. In the current study, we examine two such variables: age and the ease with which people feel they can express their identity in the national context. Participants were drawn from three waves (2008-12) of the biannual New Zealand General Social Survey (NZGSS). The NZGSS consists of a number of questions related to well-being. The current study utilised the questions related to one's sense of belonging to New Zealand, ease to express one?s identity in New Zealand, and mental health. When controlling for physical health, standard of living, and several demographic control variables, there was a clear relationship between one?s sense of belonging to New Zealand and mental health. Further, this relationship was stronger for older than younger participants. Finally, the ease with which participants felt they could express their identity in New Zealand partially mediated the relationship. Future research should elucidate which specific aspects of their identity people feel is constrained in the national context. Publisher PDF

Despite a growing understanding of the triggers for suicidal thoughts and behavior, little is known about the mechanisms that prevent people from killing themselves. The goal of the present study was to use publicly available Reddit data to better understand the reasons that people give for not following through with a potentially lethal suicide attempt. Threads containing key terms (e.g., "kill yourself") within the subreddit /r/AskReddit were collected and all top posts from these threads were thematically coded. Across the posts collected, 11 different themes were identified; friends and family, curiosity and optimism about the future, spite, purpose, transience, hobbies, animals/pets, fear of survival, fear of pain, death and/or the afterlife, apathy/laziness, and intervention. Some additional themes were captured in an "other" category, and a twelfth theme, use of pharmaceutical drugs, was identified, but not discussed. These findings provide a broad overview about the proximal protective factors that directly stopped people from making a suicide attempt. They also illustrate the potential for Reddit as platform through which to better understand factors that may help to identify and support those in suicidal crisis. Such insight may help to inform intervention and prevention strategies for suicide and those in suicidal crisis.

Kwang-Hee Shin,1 Ji-Young Jeon,2 Kyungho Jang,2 Tae-Eun Kim,3 Min-Gul Kim2,4 1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; 3Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea; 4Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea Purpose: The aim of this study was to evaluate the dose-proportional pharmacokinetic characteristics of pregabalin following the administration of GLA5PR GLARS-NF1 tablets (150, 300, 450, and 600 mg) in the fed state.Subjects and methods: An open-label, randomized, single-dose, parallel study was conducted in 40 eligible subjects who were randomly assigned to receive a single 150, 300, 450, or 600 mg dose of GLA5PR GLARS-NF1. Serial blood samples were collected before and after dosing for 36 hours, and plasma concentrations were determined using liquid chromatography-tandem mass spectrometry. Safety profiles were evaluated throughout the study (trial registration number: NCT02327000).Results: Thirty-seven subjects completed the studies. The area under the plasma concentration-time curve up to the last measurable concentration of pregabalin exhibited dose proportionality following administration of GLA5PR GLARS-NF1 tablets from 150 to 600 mg while its maximum plasma concentration showed dose proportionality at a dose range of 150–450 mg. The safety evaluations showed no clinically significant finding after administration of GLA5PR GLARS-NF1 tablets (150, 300, 450, and 600 mg) in the fed state.Conclusions: The dose-proportional properties of GLA5PR GLARS-NF1 150–450 mg tablets were determined. Keywords: gamma-aminobutyric acid analog, GABA analog, maximum concentration, safety evaluation, Korean

Background LCB01-0371 is a new oxazolidinone antibiotic, which targets most Gram-positive organisms. High rates of adverse reactions including myelosuppression have been reported for existing oxazolidinones, limiting their long-term use. Objectives The safety, tolerability and pharmacokinetics (PK) of 21 day multiple oral administrations of LCB01-0371 in healthy male subjects (clinicaltrials.gov: NCT02540460) were investigated. Methods In this randomized, double-blind, placebo-controlled study, subjects received 800 mg of LCB01-0371 once or twice daily or 1200 mg of LCB01-0371 twice-daily for 21 days in a fasting state. Safety and tolerability profiles including laboratory tests were evaluated during the study and on a post-study visit and the results were analysed using repeated-measures analysis of variance (RM-ANOVA). Serial blood samples for PK analysis were collected up to 12 h after dosing on day 21. Results A total of 40 subjects were enrolled and 34 subjects completed the study. Two subjects dropped out according to stopping rules. In the 1200 mg twice-daily dose group, the absolute value of red blood cell count, haematocrit and haemoglobin decreased by 500 × 106/L (6.5%), 4.5% (6.8%) and 1.6 g/dL (6.9%), respectively, after 21 day administrations of LCB01-0371. However, mean relative changes from baseline of all haematology values were not significantly different among doses, including placebo (all, P

A number of recent studies have revealed that taking part in a sail-training-based Adventure Education Programme elevates youths’ self-esteem. Across two studies, we sought to examine the extent to which youths’ sense of belonging contributed to this increase in self-esteem. Study 1 revealed that participants who completed the voyage showed an increase in self-esteem from the first to the last day of the voyage. Partial correlation revealed that group belonging made a unique contribution to this change. Study 2 replicated Study 1 and, further, demonstrated that the relationship between group belonging and self-esteem was not a function of self-efficacy or group esteem. Such findings suggest that an important contributing factor to the benefits of sail-training interventions is their potential to satisfy psychological needs, in this case the need to belong.

Context A fixed-dose combination (FDC) of candesartan and rosuvastatin was recently developed for the treatment of cardiovascular disease and expected to enhance patient compliance. Objective This study was performed to compare the single-dose pharmacokinetic properties and tolerability of DP-R208 (candesartan and rosuvastatin FDC) to those of each component administered alone in healthy Korean male volunteers. Materials and methods A total of 40 healthy Korean volunteers were enrolled in this randomized, open-label, single-dose, two-treatment, two-way crossover study. During each treatment period, subjects received the test formulation (FDC tablet containing candesartan and rosuvastatin) or reference formulation (co-administration of candesartan and rosuvastatin). Plasma samples were collected pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, and 48 hours post-dose. Safety and tolerability were assessed by the evaluation of adverse events (AEs), physical examinations, laboratory assessments, 12-lead electrocardiograms (ECGs), and vital sign measurements. Results The 90% confidence intervals (CIs) of the geometric least-square mean ratios of Cmax, AUClast, and AUCinf were 0.86 - 1.00, 0.92 - 1.04, and 0.92 - 1.03 for candesartan, and 0.88 - 1.06, 0.91 - 1.08, and 0.91 - 1.03 for rosuvastatin, respectively. All of the AEs were mild, and there was no significant difference in the incidence of AEs between the formulations. Furthermore, the pharmacokinetic properties of the test and reference formulations met the regulatory criteria for bioequivalence. Discussion and conclusion: Both formulations were safe and well tolerated, and no significant difference was observed in the safety assessments of the treatments. .

Kyungho Jang,1,2,* Min-Kyoung Kim,3,4,* Jaeseong Oh,1 SeungHwan Lee,1 Joo-Youn Cho,1 Kyung-Sang Yu,1 Tai Kiu Choi,3 Sang-Hyuk Lee,3,4 Kyoung Soo Lim4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Medical School, Jeonju, 3Department of Psychiatry, 4Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea *These authors contributed equally to this work Purpose: Oseltamivir is widely used in the treatment and prophylaxis of influenza A and B viral infections. It is ingested as an oral prodrug that is rapidly metabolized by carboxylesterase 1 (CES1) to its active form, oseltamivir carboxylate. Dexamethasone is also used in the treatment of acute respiratory distress syndrome, a severe complication of influenza; however, its influence on the pharmacokinetics (PK) of oseltamivir is controversial. The aim of this study was to investigate the effects of coadministering oseltamivir and dexamethasone on the PK of oseltamivir in healthy volunteers. Methods: An open-label, two-period, one-sequence, multiple-dose study was conducted in 19 healthy male volunteers. Oseltamivir (75mg) was orally administered on Day 1 and Day 8, and dexamethasone (1.5mg) was administered once daily from Day 3 to Day 8. Serial blood and urine samples were collected for PK analysis of oseltamivir and oseltamivir carboxylate on Day 1 and Day 8. Oseltamivir and oseltamivir carboxylate concentrations in plasma and urine were determined using liquid chromatography–tandem mass spectrometry. Results: Area under the plasma concentration–time curve (AUC) of oseltamivir and oseltamivir carboxylate decreased after dexamethasone treatment for 6 days. The geometric mean ratio (90% confidence interval) of the metabolic ratio (oseltamivir carboxylate AUC0–48h/oseltamivir AUC0–48h) was 0.92 (0.87–0.97). The amount of unchanged oseltamivir excreted in urine increased by 14% after dexamethasone treatments. Conclusion: Coadministration of dexamethasone with oseltamivir slightly decreased systemic exposure to oseltamivir and oseltamivir carboxylate in healthy volunteers. This result suggests that CES1 is inhibited by dexamethasone in humans. However, coadministration of oseltamivir and dexamethasone did not appear to have a clinically relevant effect on the PK of oseltamivir; based on these results, dexamethasone can be coadministered with oseltamivir. Keywords: carboxylesterase, steroid, influenza, ARDS

In emergency dispatching at 119 Command & Dispatch Center, some inconsistencies between the `standard emergency aid system` and `dispatch protocol,` which are both mandatory to follow, cause inefficiency in the dispatcher`s performance. If an emergency dispatch system uses automatic speech recognition (ASR) to process the dispatcher`s protocol speech during the case registration, it instantly extracts and provides the required information specified in the `standard emergency aid system,` making the rescue command more efficient. For this purpose, we have developed a Korean large vocabulary continuous speech recognition system for 400,000 words to be used for the emergency dispatch system. The 400,000 words include vocabulary from news, SNS, blogs and emergency rescue domains. Acoustic model is constructed by using 1,300 hours of telephone call (8 kHz) speech, whereas language model is constructed by using 13 GB text corpus. From the transcribed corpus of 6,600 real telephone calls, call logs with emergency rescue command class and identified major symptom are extracted in connection with the rescue activity log and National Emergency Department Information System (NEDIS). ASR is applied to emergency dispatcher`s repetition utterances about the patient information. Based on the Levenshtein distance between the ASR result and the template information, the emergency patient information is extracted. Experimental results show that 9.15% Word Error Rate of the speech recognition performance and 95.8% of emergency response detection performance are obtained for the emergency dispatch system.

BACKGROUND: Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies. METHODS: We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted. RESULTS: Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%). CONCLUSIONS: The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13139-019-00593-y) contains supplementary material, which is available to authorized users.

A clinical trial management system (CTMS) is a comprehensive program that supports an efficient clinical trial. To improve the environment of clinical trials and to be competitive in the global clinical trials market, an advanced and integrated CTMS is necessary. However, there is little information about the status of CTMSs in Korea. To understand the utilization of current CTMSs and requirements for a future CTMS, we conducted a survey on the subjects related to clinical trials. The survey was conducted from July 27 to August 16, 2017. The total number of respondents was 596, and 531 of these responses were used. Almost half of the respondents were from hospitals (46%). The proportion of respondents who are currently using a CTMS was the highest for contract research organizations at 59%, whereas the proportion used by investigators was 39%. The main reason for not using a CTMS was that it is unnecessary and expensive, but it showed a difference between workplaces. Many respondents frequently used CTMSs to check the clinical trial schedule and progress status, which was needed regardless of workplace. While two-thirds of users tended to be satisfied with their current CTMS, there were many users who felt their CTMS was inconvenient. The most requested function for a future CTMS was one that could be used to manage the project schedule and subject enrollment status. Additionally, a systematic linkage to electronic medical records, including prescription and laboratory test results, and a function to confirm the participation history of subjects in other hospitals were requested.

Age-related physiological changes are known to alter the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Metformin is commonly used as first-line medication for management of diabetes in elderly patients. However, the PK and PD of metformin have not been sufficiently studied in elderly subjects. Here, 12 elderly subjects, aged 65 to 85 years, and 20 younger healthy volunteers were orally administered 750 mg of metformin 2 hours after dinner, followed by administration of a second dose (500 mg) 12 hours later. An oral glucose tolerance test (OGTT) was performed 2 hours after the second dose, with 75 g of glucose administered. Blood samples were collected at specific time points after the second metformin dose for the assessment of PK and the glucose-lowering effect of metformin. Elderly subjects exhibited 1.7 and 2.0 times higher average Cmax and AUC∞ than the younger subjects, respectively (P = .007 and .001, respectively), and t1/2 was comparable between the elderly and younger subjects. However, relative glucose level changes from baseline after metformin administration tended to be lower in elderly subjects. Systemic exposure to metformin was elevated by 50% or more in elderly subjects, whereas the glucose-lowering effect was similar compared to younger subjects after 2 doses of metformin.

We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography-electrospray ionization-tandem mass spectrometry. When metformin was co-administered with pyrimethamine, its area under the concentration-time curve from 0 to 12 h was 2.58-fold greater (p

Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p -aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration ( C max ) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUC τ ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean C max and AUC τ , respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.)

BACKGROUND Alcohol use among university students is common, and those who drink often choose to drink heavily (ie, 4 or more drinks per session for women or 5 or more for men). Web-based interventions (WBIs), in which students complete assessments and receive personalized feedback about their alcohol use, and ecological momentary interventions (EMIs), which use mobile devices as a method of delivering intervention information, are 2 methods that have had some success in reducing alcohol use among university students. OBJECTIVE The aim of this study was to investigate the effectiveness of a combined WBI and EMI intervention to reduce alcohol use among university students. METHODS The study is a 3-arm randomized controlled trial. Participants will be randomized into either a WBI+EMI condition, a WBI-only condition, or an assessment-only control. Our sample will consist of first-year university students, recruited through 5 residential colleges at the University of Otago, New Zealand. All participants will complete an online survey at baseline (ie, before Orientation Week); those in the WBI-only and WBI+EMI conditions will immediately receive personalized feedback (ie, the WBI), whereas participants in the assessment-only condition will receive no feedback. In addition, participants randomized into the WBI+EMI, but not those in the WBI-only or assessment-only groups, will receive 8 Orientation Week (2 per day on nights with large social events) and 6 academic year EMIs (delivered fortnightly). Participants in all conditions will complete brief surveys at the end of the first and second semester and report their weekend alcohol use fortnightly throughout each semester via ecological momentary assessments. RESULTS The primary hypothesis is that participants in the WBI+EMI group will consume significantly fewer drinks during weekends in their first semester at university compared with WBI-only and assessment-only groups. Secondary hypotheses are that, when compared with the WBI-only and assessment-only groups, the WBI+EMI group will report consuming fewer drinks during Orientation Week, report experiencing fewer negative alcohol-related consequences after first semester, and report lower Alcohol Use Disorder Identification Test-Consumption scores following their first semester. CONCLUSIONS This study adds to a growing body of work investigating the utility of WBIs and EMIs in curbing alcohol consumption. In addition, the study will help to inform policy approaches aimed at curbing alcohol consumption and alcohol-related harm in university students. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12618000015246; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374104&isReview=true (Archived by WebCite at http://www.webcitation.org/6z9jRLTz6) REGISTERED REPORT IDENTIFIER RR1-10.2196/10164

Economic education has occupied a preeminent and indispensable place in the university curricula in Korea for decades. Considered as one of the most rigorous and prestigious majors, economics departments in Korean universities have invariably attracted applicants of superior grades and qualifications. With this background, this chapter summarizes the current status of economic education in universities in Korea. This chapter also reviews the assessment tools designed to measure economic understanding along with their main characteristics and provide detailed information on the assessment efforts to measure economic literacy at the college level and their main results, more specifically, Test of Understanding of College Economics (TUCE), College Scholastic Ability Test (CSAT), and two nationally accredited qualification tests: the Test of Economic Sense and Thinking (TESAT) and the Test of Economic and Strategic Business Thinking (MK TEST). This chapter calls for a development of a standardized international assessment tool that can measure the economics understanding of college students and adults in hopes to more precisely identify the level of economics understanding of Korean college students by country to country comparison among their similarly situated international peers.

VVZ-149, a dual antagonist of GlyT2 and 5HT2 A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early-stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ-149 injections in healthy male volunteers were explored in a randomized, double-blind, single- and multiple-ascending-dose (SAD and MAD, respectively), placebo-controlled clinical study. Subjects randomly received a 4-hour intravenous infusion of 0.25-8 mg/kg VVZ-149 or placebo in the SAD study (n = 46) or a 4-hour intravenous infusion of 4-7 mg/kg VVZ-149 or placebo twice daily for 3 days in the MAD study (n = 20). Serial blood and urine samples were collected for the pharmacokinetic analysis of VVZ-149 and its active metabolite (VVZ-368). Noncompartmental and compartmental pharmacokinetic analyses were performed. Various dosing scenarios were simulated to identify the adequate dosing regimen for the subsequent trials. Plasma exposure to VVZ-149 and VVZ-368 showed a dose-proportional increase. VVZ-149 did not accumulate in the plasma, whereas the plasma concentration of VVZ-368 increased by 1.23- to 2.49-fold after the fifth and sixth doses, respectively, in the MAD trial. Among the simulated dosing regimens, a loading dose followed by a maintenance dose was found to be an optimal dosing regimen, yielding the effective concentration estimated from animal studies in rat models of neuropathic or inflammatory pain. Single- or multiple-dose administration of VVZ-149 was generally well tolerated. These results showed that 0.5-8 mg/kg VVZ-149 exhibited linear pharmacokinetic characteristics and can be safely administered in further clinical studies.

This study looks into the financial literacy between Korean and U.S. high school students. The mean scores for Korean students fell between those for U.S. students with and without FFFL, but much closer to those with FFFL. Korean students tended to be stronger in such contents as “earning income.” A comparison of financial literacy based on the Bloom's cognitive level indicates that Korean students showed relatively strong financial literacy at the cognitive level of knowledge, but weak financial literacy at higher cognitive levels of comprehension and application.

This paper presents an alternative maximum likelihood estimation method for partially identified vector autoregressive models. This method might be especially useful to handle very large systems of variables by reducing the dimension of the likelihood space. As an application, we consider an open economy model to investigate the effects of monetary policy on exchange rates and term structures. We find that exchange rates tend to overshoot and term structures have hump-shaped responses to monetary policy shocks.

This study was a phase 1, single-center, randomized, double-blind, placebo-controlled, single-dosing, and dose-escalating study of intravenous SAL200. It is a new candidate drug for the treatment of antibiotic-resistant staphylococcal infections based on a recombinant form of the phage endolysin SAL-1. The study evaluated the pharmacokinetics, pharmacodynamics, and tolerance among healthy male volunteers after the intravenous infusion of single ascending doses of SAL200 (0.1, 0.3, 1, 3, and 10 mg/kg of body weight). SAL200 was well tolerated, and no serious adverse events (AEs) were observed in this clinical study. Most AEs were mild, self-limiting, and transient. The AEs reported in more than three participants were fatigue, rigors, headache, and myalgia. No clinically significant values with respect to the findings of clinical chemistry, hematology, and coagulation analyses, urinalysis, vital signs, and physical examinations were observed, and no notable trends in our electrocardiogram (ECG) results for any tested dose were noticed. A greater-than-dose-proportional increase with regard to systemic exposure and the maximum serum concentration was observed when the SAL200 dose was increased from 0.1 mg/kg to 10 mg/kg. This investigation constitutes the first-in-human phase 1 study of an intravenously administered, phage endolysin-based drug. (This study has been registered at ClinicalTrials.gov under identifier NCT01855048 and at the Clinical Research Information Service [ https://cris.nih.go.kr/cris/ ] under identifier KCT0000968.).

International comparisons of economic understanding generally require a translation of a standardized test written in English into another language. Test results can differ based on how researchers translate the English written exam into one in their own language. To confirm this hypothesis, two differently translated versions of the Basic Economics Test (BET) (Walstad, Rebeck, and Butters 2010a) were given to elementary school students in Korea. We found the possibility of overestimating or underestimating the levels of economic understanding by various sources of translation bias. Therefore, it is important to carefully interpret the assessment results of international comparisons. Our study is applicable not only to international comparisons of economic literacy but also to any comparison of knowledge across cultures or languages within a country.

The authors describe key aspects of precollege and undergraduate economic education in Korea. They show that precollege students seem to have low economics literacy due to problems with the curriculum and insufficient training of teachers. At the undergraduate level, they show that economics departments have more male students than female students and that the employment rate for economics majors is lower than for business majors. They hope to draw more of Korean economists' attention to research initiatives in economic education.

To report the clinical characteristics of bacterial keratitis associated with epidemic keratoconjunctivitis (EKC) and to evaluate the risk factors for bacterial keratitis development in eyes with EKC.After 108 patients diagnosed as EKC were retrospectively reviewed, clinical characteristics and incidence of bacterial keratitis-associated EKC were described. To analyse the effect of steroid use and the methicillin-resistant Staphylococcus aureus (MRSA) colonization in conjunctiva on developing bacterial keratitis, HCU-stayed children (n=43) were divided into two groups: those with and those without bacterial keratitis. Other risk factors such as gestational age, duration of hospitalization, MRSA colonization rate of other sites, and interval between follow-ups were evaluated in neonates who stayed in a neonatal intensive care unit (NICU; n=29).Eight out of nine bacterial keratitis developed in HCU-stayed children. All the eight cases of bacterial keratitis occurred in neonates and infants. MRSA keratitis was found in seven hospitalized infants. The incidence of bacterial keratitis was significantly higher in HCU-stayed children than in outpatients (P=0.03), although it never occurred in HCU-stayed adults. The culture-positive rate of MRSA in conjunctiva (P=0.047) and topical use of steroid (P=0.01) were significantly higher in HCU-stayed children who carried bacterial keratitis. The incidence of bacterial keratitis was significantly related with the longer interval of follow-up in early EKC period in NICU in patients (P=0.009).Infants and neonates show high tendency of MRSA keratitis accompanied with EKC, especially if they were in HCU, applied topical steroid or followed with long interval.

Age-related physiological changes are known to alter the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Metformin is commonly used as first-line medication for management of diabetes in elderly patients. However, the PK and PD of metformin have not been sufficiently studied in elderly subjects. Here, 12 elderly subjects, aged 65 to 85 years, and 20 younger healthy volunteers were orally administered 750 mg of metformin 2 hours after dinner, followed by administration of a second dose (500 mg) 12 hours later. An oral glucose tolerance test (OGTT) was performed 2 hours after the second dose, with 75 g of glucose administered. Blood samples were collected at specific time points after the second metformin dose for the assessment of PK and the glucose-lowering effect of metformin. Elderly subjects exhibited 1.7 and 2.0 times higher average Cmax and AUC∞ than the younger subjects, respectively (P = .007 and .001, respectively), and t1/2 was comparable between the elderly and younger subjects. However, relative glucose level changes from baseline after metformin administration tended to be lower in elderly subjects. Systemic exposure to metformin was elevated by 50% or more in elderly subjects, whereas the glucose-lowering effect was similar compared to younger subjects after 2 doses of metformin.

This paper presents an alternative approach to two-step maximum likelihood estimation of structural vector error correction models that are partially identified with long-run restrictions. We generalize the existing literature by allowing for over-identifying restrictions.