Earticle

Background: Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. Methods: Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. Results: EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities. Conclusion: Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.

Objective: We investigated arthralgia and myalgia associated with the use of oral bisphosphonate (BP) by conducting a survey of patient. Methods: The pharmacists conducted a survey between 1 Oct 2019 and 30 Sep 2020 among patients who were dispensed BP in community pharmacies to assess their demographic and medical characteristics, and their experiences with, and process for pain. Logistic regression analyses were performed to find the risk factors associated with the pain, and the odds ratios (OR) and 95% confidence intervals (CI) were determined. Results: A total of 160 patients who used BP participated in the survey (74 [46.3%] used risedronate; 61 [38.1%] used alendronate; 23 [14.4%] used ibandronate), and 20 (12.5%) of them experienced pain. Significant statistical differences of the characteristics between patients who experienced pain or not were observed regarding menopause, and parity. Compared with women who had one or two parity, women who had more than three parity were associated with the decreased risk of pain (OR, 0.24; 95% CI, 0.04-0.98). Moreover, steady exercise was associated with the decreased risk of pain compared to less exercise (OR, 0.37; 95% CI, 0.14-0.98). Conclusion: Our findings suggest that the risk of pain in BP-treated patients might be different regarding the different ingredients of BP, and dosing frequency. This survey highlights a need for a further safety research to understand the factors influencing the pain associated with the BP treatment.

Objective: PD-1 inhibitors have demonstrated improved health outcomes in cancer patients. PD-1 inhibitors are well-tolerated and associated with immune-related adverse events. The objectives of this study are to analyze use patterns of PD-1 inhibitors in patients with cancer and to investigate the incidence of thyroid-related adverse reactions in patients treated with PD-1 inhibitors. Methods: The study included patients who had been administered PD-1 inhibitors (either nivolumab or pembrolizumab) at the Samsung Medical Center between October 1, 2016 and June 30, 2017. Data was collected from electronic medical records and tested using Mann-Whitney tests and Chi-Square tests for statistical significance. Associations between PD-1 inhibitors and incidence of adverse events were tested using Cox regression for age, gender, BMI, ECOG PS and medication. Results: Two hundred fifteen patients were identified as eligible for analyses. Thyroid-related adverse events occurred in 20% of patients (n=43). Thyroid function tests (TFTs) was performed in 109 patients (50.7%). Positive results of PD-L1 testing were found in 53.2% of the 94 patients who had the test. Approved doses of nivolumab (3 m/kg) and pembrolizumab (200 mg) were administered in 70.4% and 53% of patients, respectively. The analysis of risk factor of thyroid-related adverse reaction did not show statistically significant differences (Cox regression). Conclusion: Thyroid-related adverse events are common in patients treated with PD-1 inhibitors and hypothyroidism is the most frequent adverse reaction. Routine TFTs monitoring is strongly recommended to evaluate thyroid function in real-world clinical practice.

Background: Cardiovascular (CV) disease is known as one of the major causes of death from disease worldwide. Statin therapy plays a pivotal role in atherosclerotic cardiovascular disease (ASCVD) lowering the LDL-cholesterol level effectively. The purpose of this study was to evaluate the association of the intensity of statin therapy in adult patients of Korea and the risk of ASCVD of the patient group. Methods: We used data from sample of patients from the Health Insurance Review and Assessment Service (HIRA-NPS- 2018). We analyzed the patterns of prescribing statins including types of statin, statin intensity, and number of patients with ASCVD or risk of ASCVD. Results: 155,512 patients were included in the analysis, and 27,950 patients (18.0%) was over 75 years. Highintensity statin usage was increased in ASCVD patients compared with the low-intensity statin use. The OR (odds ratio) of highintensity statin were increased in myocardial infarction patients compared with low-intensity statin use showing the highest OR; 12.40 (95% CI; 9.48-16.22). At patient groups of angina, ischemic heart disease and carotid disease, high-intensity statin prescription rate was increased compared with low-intensity statin. However, there was no statistical significance between both statin prescription rates in patients of peripheral arterial disease, abdominal aneurysm, diabetic mellitus and atherosclerosis. Conclusion: The statin prescription rate showed intensity increasing tendency according to the risk of ASCVD. More aggressive statin therapy might be beneficial for the ASCVD patients based on the recent guidelines of dyslipidemia.

Background: The treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT) for intraocular pressure (IOP) reduction is recommended to proceed with the use of the compound. Therefore, this study aimed to evaluate the efficacy and safety of brinzolamide combination therapy on POAG and OHT following the subgroup analysis among types of brinzolamide combined medications. Methods: By June 2019, PubMed, EMBASE and Cochrane Library were searched to find a study that met our inclusion criteria. Based on randomized control trials (RCTs), we collected studies that tested the brinzolamide combination therapy in POAG and OHT patients, and analyzed the literature identified by the results of the study on IOP reduction and adverse reactions. Results: A total of 13 literature was collected to conduct an analysis including 2,197 patients. The intervention included brinzolamide combination therapies, combined with timolol, brimonidine, PGA or combined with both brimonidine and PGA. The analysis showed significant decreasing tendency for values at morning and end treatment per day in the use of brinzolamide combination therapy in the absolute IOP change (mean difference (MD) −1.41; 95% CI −1.92, −0.90; p<0.001 vs. MD −1.46; 95% CI −2.03, −0.89; p<0.00001, respectively). We could see higher adverse reactions in the brinzolamide combination group using intervention (odds ratio 1.43; 95% CI 1.20, 1.71; p<0.0001). Conclusion: Regarding IOP reduction in POAG and OHT patients, brinzolamide combination therapy is more effective but less safe than control treatment, which diverse among types of combined medications. Thus, more individualized therapy should be applied in real-world practice.

Objective: Taking action on health inequalities starts with the production of information laying out the problems of inequalities, but Korean society has no national database to view related data at a glance. This study aimed to compare Korean national database with the Public Health Profile (PHP), a health inequality database of the UK. Methods: Data were collected from the websites of government and relevant organizations in the both countries between March and August 2020, which was updated in August 2021. Two themes including Co-occurring substance misuse and mental health issues in mental health and INteractive Health Atlas of Lung conditions in England were selected for comparison in terms of data accessibility, data usability and data visualization. Results: The British PHP is being served on a web-based platform, Fingertips. The data collected at the regional level were presented on 31 health inequality themes. The data are displayed at a level that can be compared between comparable communities, and visualized into various tables and figures. Comparable Korean data were scattered in several themes and websites, and mostly provided as a 17 administrative region base, which was too vast to make a meaningful comparisons. Conclusion: The findings proposed several considerations which could be useful for establishing a database of health inequality in the Korean society.

Background: Sarcopenia is a skeletal muscle disorder that involves the loss of muscle mass and function. Handgrip strength (HGS) is the most commonly used tool to assess muscle strength to diagnose sarcopenia. HGS is also associated with various diseases and health outcomes. Thus, we aimed this study to examine the HGS status in Korean adults and relevant factors of HGS. Methods: Data was obtained from the 7th Korea National Health and Nutrition Examination Survey (KNHANES), a population-based nationwide survey. The estimated mean value of HGS was calculated in each age group. The mean HGS in men and women aged over 40 was compared according to the household income level, lifestyle factors, and comorbidities. Results: A total of 16,708 participants were included in this study. The mean HGS showed a maximum value in the 30s for both men and women, and then tended to decrease with increasing age. When analyzed for people aged 40 or older, the mean HGS was significantly higher in the current or past smoker, drinker, and aerobic exercise groups in both men and women. The mean HGS was lower in the group with comorbidities such as hypertension, dyslipidemia, type 2 diabetes, and bone diseases. Conclusion: Our study found that the mean HGS was significantly different between those with and without underlying chronic diseases. In groups with relevant comorbidities, close monitoring for the development of sarcopenia and taking preventive measures such as exercise and nutritional support may be recommended.

Background: Pembrolizumab, an anti-cancer drug, is known to increase the activity of the immune system, leading to side effects called immune-related adverse events (irAE), including type 1 diabetes. This study analyzed the correlation between blood glucose level and pembrolizumab administration and investigated the covariates that affect those changes in cancer treatment. Methods: The information of 133 adult cancer patients was obtained from the electronic medical record (EMR) to identify the changes in random blood glucose (RBG) levels during the pembrolizumab treatment. Subjects were classified into subgroups according to their baseline RBG level, history of diabetes, and the use of steroids, and linear regression analysis was conducted. In addition, a secondary analysis was performed within the group of subjects having a strong correlation to glycemic change, which was based on the Pearson correlation coefficient being less than -0.7 or greater than +0.7. Univariate and multivariate logistic regressions were conducted to identify the risk factors to glycemic increase. Results: The RBG level tended to descend without significant differences in total patients during the administration period of pembrolizumab. Despite the insignificance, the logistic regression analysis presents that the odds ratios of baseline RBG less than 130 mg/dL, prophylactic steroid use, and higher dose of pembrolizumab per cycle (mg/kg/ cycle) were greater than 1. Conclusions: Prophylactic administration of steroids and a higher dose of pembrolizumab per cycle may increase the blood glucose level as irAE in cancer patients with a strong tendency to glycemic change.