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Abstract Background Estrogen therapy in early menopausal women decreases the risk of coronary heart disease and parenteral, but not oral, estrogen is reported to reduce blood pressure (BP). Progestogens are typically added to estrogens to prevent unopposed endometrial stimulation. The effects of progestogen on BP have been less well studied to date. This study was conducted to explore the impacts of micronized progesterone (MP4) combined with percutaneous estradiol gel (PEG) on hemodynamics in postmenopausal Korean women with grade 1 hypertension. Methods Fifty-two postmenopausal women (aged 49–75 years) with systolic BP (SBP) of 140–160 mmHg or diastolic BP (DBP) of 90–100 mmHg were randomly assigned for 12 weeks to placebo (n = 16), estrogen therapy (ET) (n = 19) with PEG (0.1 %, 1 g./d), or estrogen + progestogen therapy (EPT, n = 17) with PEG and MP4 (100 mg/d). The primary endpoint was ambulatory BP and the secondary endpoints were arterial stiffness as brachial–ankle pulse-wave velocity (baPWV) and aortic parameters on applanation tonometry. Results One woman in the ET group dropped out, so 51 participants were finally analyzed. Outcome measures for ambulatory BP and arterial stiffness were not different between groups. Within-group comparisons showed that EPT significantly decreased daytime heart rate and baPWV: the changes from baseline (mean ± standard deviation) were − 2.5 ± 5.7 bpm (P = 0.03) and − 0.6 ± 1.4 m/s (P = 0.04), respectively. After adjusting for baseline, linear regression analysis revealed a significant difference in the relationship between baseline and 12-week baPWV among groups (P = 0.02). The relationship was significantly different between placebo and ET (P = 0.03) and EPT (P = 0.01), respectively, but not between ET and EPT. Additionally, pooled results of active treatments disclosed that SBP, DBP, PWV, and augmentation index at the aorta were significantly reduced relative to baseline. Conclusions There was no difference in ambulatory BP between ET and EPT in postmenopausal Korean women with grade 1 hypertension. Further, ET and EPT similarly decreased baPWV from baseline as compared with placebo. MP4 might not adversely influence estrogen effects on ambulatory BP and arterial stiffness. Trial registration Clinical Research Information Registry, KCT0005405, Registered 22 September 2020 - Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do?all_type=Y&search_page=L&pageSize=10&page=1&seq=17608&search_lang=E .

ObjectiveThe aim of this study was to investigate the prevalence of abnormal vaginal microorganisms in pregnant women according to trimester, and to determine whether the presence of abnormal vaginal colonization is associated with higher risk of miscarriage or preterm delivery. Furthermore, we analyzed delivery outcomes according to individual microorganism species.MethodsWe included pregnant women who underwent vaginal culture during routine prenatal check-up between January 2011 and June 2016. We compared delivery outcomes according to the presence or absence of abnormal vaginal flora grouped by trimester.ResultsThis study included 593 singleton pregnancies. We classified participants into 3 groups, according to the trimester in which vaginal culture was performed; 1st trimester (n=221), 2nd trimester (n=138), and 3rd trimester (n=234). Abnormal vaginal colonization rate significantly decreased with advancing trimester of pregnancy (21.7% for 1st, 21.0% for 2nd, 14.5% for 3rd; P=0.048). Abnormal vaginal colonization detected in the 2nd trimester but not in 1st trimester was associated with a significant increase in preterm delivery before 28 weeks of gestation (6.9% vs. 0%; P=0.006). Among abnormal vaginal flora isolated in the 2nd trimester, the presence of Klebsiella pneumonia was identified as significant microorganism associated with preterm delivery before 28 weeks of gestation (50% vs. 0.7% for K. pneumonia; P=0.029).ConclusionThere is an association between abnormal vaginal colonization detected in the 2nd trimester and preterm delivery before 28 weeks. K. pneumonia has been identified as the likely causative microorganisms.

Background: Several preclinical and clinical studies have suggested that BRCA-mutation carriers may have decreased ovarian reserve. However, data in this area are limited and inconsistent, especially in young breast cancer patients.Objective: This study evaluated the association between BRCA mutation status and serum anti-Müllerian hormone (AMH) level in young, reproductive-aged patients with breast cancer.Materials and Methods: Patients ≤ 40 years of age with breast cancer and who had known BRCA status and baseline serum AMH level at Samsung Medical Center, Seoul, Korea, were considered for inclusion. A total of 52 BRCA mutation carriers (27 BRCA1 and 25 BRCA2) and 264 non-carriers were selected for analyses. The serum level of AMH was compared according to presence of a BRCA mutation, and linear and logistic regression analyses were performed to evaluate the association between BRCA mutation and serum AMH level.Results: No difference was found in clinical characteristics between BRCA-mutation carriers and non-carriers. Subjects with any BRCA mutation had a significantly lower median AMH than those without a mutation (2.60 vs. 3.85 ng/mL, 32% reduction, P = 0.004). Linear regression analysis showed a significant negative association between BRCA mutation and AMH level. In addition, logistic regression demonstrated non-significantly increased odds of mutation carriers having AMH < 1.2 ng/mL. However, no difference was found between BRCA1/2 mutations.Conclusions: Breast cancer patients with BRCA mutation have significantly lower serum AMH level. Fertility preservation should be considered more aggressively in young breast cancer patients with BRCA mutation.

Abstract Background Introducing more generics has been a successful strategy for lowering pharmaceutical prices and expenditure. However, the effect of the strategy depends on the pricing schemes for generics. We aimed to update the South Korean generic markets in terms of effective competition, and to examine the effects of number of manufacturers and price variance on pharmaceutical expenditure. Methods We constructed balanced panel data provided by the Health Insurance Review and Assessment Service covering 726 reimbursed substances from 2019 to 2023. We developed original indicators to analyze the generic markets: the maximum-minimum price variance (MMPV) and the maximum-weighted price variance (MWPV). Panel regression with fixed and time-fixed effects was used. Results Over the study period, the number of manufacturers increased from 17.81 in 2019 to 20.98 in 2020 and then decreased to 18.70 in 2023. The MMPV increased from 204.70 in 2019 to 230.07 in 2022 and then decreased slightly to 225.34 in 2023. The MWPV increased from 59.70 in 2019 to 72.58 in 2023. Two types of segmented markets were noteworthy: low use of low-cost generics with sufficient manufacturers and high use of low-cost generics with insufficient manufacturers. In the fixed and time-fixed effects panel analyses, the MWPV presented a negative association with the number of manufacturers and a positive association with the MMPV. Conclusions A newly introduced tiered pricing scheme, designed to differentiate generic prices, was associated with a decrease in the number of manufacturers and an increase in price dispersion. The pricing schemes for generics should be designed with price variance in mind and limit the number of too many generics in South Korea.

Abstract Hot flashes (HF) are a common adverse event of prolonged tamoxifen use in women with estrogen receptor-positive breast cancer, impacting psychiatric health and quality of life. While desvenlafaxine does not interact with tamoxifen, its efficacy and safety in breast cancer patients remain unstudied. This phase 3, four-week, multi-center, three-arm, parallel-group, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of desvenlafaxine for treating HF in women with breast cancer taking tamoxifen, assessing potential differential effects in patients with psychiatric and inflammatory conditions. Between December 2017 and February 2019, 57 women aged 19 or older, regularly taking tamoxifen as adjuvant therapy, experiencing moderate-to-severe HFs for more than a month, were randomized to receive desvenlafaxine 50 mg/day (D-50), desvenlafaxine 100 mg/day (D-100), or placebo for four weeks. The primary endpoint was the change rate in HF scores over four weeks, with adverse events as a secondary endpoint. Both desvenlafaxine arms demonstrated greater HF score reductions compared to placebo: D-50 (2.20 points/week, 95% CI: 0.71, 3.68) and D-100 (2.34 points/week, 95% CI: 0.92, 3.76). Notably, D-50 arm showed significantly greater efficacy in patients with depression or elevated inflammation. Desvenlafaxine offers an effective and safe treatment regimen for HF in women with breast cancer taking tamoxifen. The presence of depression and inflammation may guide optimal desvenlafaxine dosing. (Trial Registration: ClinicalTrials.gov Identifier: NCT02819921)

IntroductionA period of exclusivity for the first generics, as part of the patent linkage system, was established in South Korea to provide an economic incentive for early generic entry. This study describes the dynamics of generic penetration and assesses the first mover market share advantages under the patent linkage system.MethodsPairs of originators and their corresponding generics granted the first generic exclusivity from 2015 to 2020 were identified. We categorized generics into first movers and latecomers, described the penetration curves of generics, and estimated the saturated market share of generics, first movers, and latecomers. Volume-based monthly prescriptions were used to describe the generics’ penetration curves. A logistic growth model was adopted to estimate the saturated market shares of generics.ResultsWe identified 28 pairs of originators and generics, presented penetration curves, and estimated generics market shares. The saturated market share of generics was 30%, and the time to saturation was approximately 33 months. The shapes of penetration varied by nationality, route, and number of generics. The existence of latecomers was associated with the decreased penetration speed over time and decreased market share of generics. However, the first mover market share advantages or latecomers’ disadvantages were consistently observed.ConclusionThe generic uptake in South Korea is delayed, limited, and context-dependent. However, first generics’ market share advantage suggests that a period of exclusivity, as part of the patent linkage system, could provide an economic incentive for early generic entrance.

BackgroundCommunity pharmacists confronted dual burdens in response to the COVID-19 pandemic by expanding the scope of pharmaceutical practices. ObjectiveThis study aimed to assess the perceived roles and functions of community pharmacies during the pandemic and to explore their updated roles after the pandemic began. MethodsWe conducted a self-reported web-based survey in October 2022. Based on Korean census data, we recruited the study participants (n=1000) through quota sampling stratified by age, sex, and region, yielding a 7.45% (1000/13,423) response rate. The questionnaires were composed of 3 sections: demographics, the roles and functions of community pharmacies during the pandemic, and the updated roles of community pharmacies during disasters. Each question in the second and third sections was rated on a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree), and each item’s mean scores and SDs were reported. The study participants were categorized into 2 groups: individuals who had a family pharmacy and those who did not. A chi-square test and ordered logistic regression analyses were conducted. ResultsOut of 1000 respondents, 418 (41.8%) had a history of COVID-19, and 639 (63.9%) had a family pharmacy. Assigning specific roles and functions to community pharmacies during the pandemic contributed to positive assessments. Respondents gave higher scores to community pharmacies that had responded appropriately (a mean Likert score of 3.66, SD .077 out of 5) and provided continuous pharmaceutical services (mean 3.67, SD 0.87) during the pandemic. The pandemic served as an opportunity to positively recognize the role of community pharmacies (mean 3.59, SD 0.83). In the ordered logistic model, having a family pharmacy was consistently associated with positive perceptions. Respondents perceived that community pharmacies collaborated with general practitioners and health authorities. However, community pharmacies need to function appropriately in terms of knowledge. The mean score of the 4 domains of community pharmacy functions was the highest for collaboration (mean 3.66, SD 0.83), followed by communication (mean 3.57, SD 0.87), responsiveness (mean 3.54, SD 0.87), and knowledge (mean 3.41, SD 0.91). ConclusionsThe pandemic resulted in interprofessional collaboration between community pharmacists and general practitioners. Family pharmacies could be a valuable asset to the comprehensive case management of patients. However, community pharmacists should have the expertise to build solid interprofessional collaborations and fulfill their expanded and updated roles.

IntroductionIn 2020, the South Korean government introduced social distancing measures, varied by region, to address the pandemic. We captured variations in social distancing measures among regions in South Korea and investigated the association between the stringency of measures and the increased incidence of violence.MethodsIncidence reports from calls to violence hotlines, including school and domestic violence and sexual harassment, from 2016 to 2021 were retrieved. The regional per capita incidence rates for each violence hotlines were calculated. Difference-in-difference design with fixed effects was used to elucidate different trends in the incidence rate of violence between regions with stringent social distancing measures and regions with looser measures.ResultsSocial distancing measures led to a decreased incidence rate of school violence and an increased incidence rate of domestic violence and sexual harassment. Different trends in the incidence of violence were noted between regions with strict social distancing measures and regions with more lenient measures. Tightened measures caused surges in domestic violence and sexual harassment.ConclusionSocial distancing measures have been an inevitable mitigation strategy against virus transmission throughout the pandemic. However, women residing in tightened social distancing measures, in particular urban areas, need more support against domestic violence.

BackgroundPrice competition has the potential to reduce health expenditures without hindering pharmaceutical innovation. However, empirical evidence on price competition after generic drugs are introduced is scarce. This study investigates product- and substance-level determinants of price competition following the entry of generics into the South Korean market.MethodsWe selected substances that were approved by the Ministry of Food and Drug Safety from 2000 to 2019, linked their corresponding pharmaceutical products, measured the degree of price competition under various scenarios, and utilized multilevel analysis to investigate the determinants of price competition.ResultsA total of 986 substances and 12,109 corresponding pharmaceutical products were identified. Only 11% of products were affected by price competition in the 10% scenario. However, the number increased to 43% when we measured price competition at the substance level. Major domestic manufacturers mainly initiated price competition at the product level, while foreign manufacturers were reluctant to initiate price competition. At the substance level, the maximum reimbursement price was a significant determinant of price competition.ConclusionPrice competition at the product level is rare in South Korea. In contrast, the market is quite price competitive at the substance level. Policy options could be introduced to encourage “discounted generic” substitution in an effort to maximize the effects of price competition at the substance level. Major domestic manufacturers are essential in the introduction of discounted generics into the South Korean health system.

IntroductionPatient and/or physician responses are a pivotal issue in designing rational cost-sharing programs under health insurance systems.ObjectivesThis study aims to understand patient and/or physician responses to cost-sharing programs designed for prescription drugs in South Korea.MethodsAs a framework, we took advantage of a tiered cost-sharing program, including from copayment to coinsurance (threshold 1) and reduced coinsurance (threshold 2). Given the hierarchical structure of prescriptions nested within patients, we utilized a multilevel analysis to assess effects of various cost-sharing programs on patient and/or physician responses using National Health Insurance claims data from 2018.ResultsWe found that a tiered cost-sharing program was effective in changing the behaviors of patients and/or physicians. Threshold 1 was found to be more effective than threshold 2 in changing their behaviors. At the prescription level, sensitivity to cost-sharing programs was associated with prescribed days of treatment and locations of prescription. In a similar vein, sensitivity to cost-sharing programs was associated with gender and age group of patients.ConclusionA simplified cost-sharing program with extended intervals should be considered to rationalize cost-sharing programs. Specifically, a cost-sharing program designed for long-term prescriptions for chronic diseases together with an emphasis on cost transparency is required to better guide price-conscious decisions by patients and/or physicians.

Abstract Background This study examined phenomenological manifestations of delirium in advanced cancer patients by examining the factor structure of the Delirium Rating Scale-Revised-98 (DRS-R-98) and profiles of delirium symptoms. Methods Ninety-three patients with advanced cancer admitted to inpatient palliative care units in South Korea were examined by psychiatrists using the DRS-R-98 and the Confusion Assessment Method (CAM). The factor structure of the DRS-R-98 was examined by exploratory structural equation modelling analysis (ESEM) and profiles of delirium were examined by latent profile analysis (LPA). Results CAM-defined delirium was present in 66.6% (n = 62) of patients. Results from the ESEM analysis confirmed applicability of the core and noncore symptom factors of the DRS-R-98 to advanced cancer patients. LPA identified three distinct profiles of delirium characterizing the overall severity of delirium and its core and noncore symptoms. Class 1 (n = 55, 59.1%) showed low levels of all delirium symptoms. Class 2 (n = 17, 18.3%) showed high levels of core symptoms only, whereas Class 3 (n = 21, 22.6%) showed high levels of both core and noncore symptoms except motor retardation. Conclusions Clinical care for delirium in advanced cancer patients may benefit from consideration of the core and noncore symptom factor structure and the three distinct phenomenological profiles of delirium observed in the present study.

Abstract Background Health systems are struggling with unprecedented drug spending and governments have devised various policy options to manage high-priced medicines. Meanwhile, some pricing and reimbursement processes are currently moving under the jurisdiction of international agreements. This study aims to understand trends in international agreements from the perspectives of pricing and reimbursement policies for newly marketed medicines. Methods We proposed the framework to interpret the international agreements as code and applied computational text analysis to understand international agreements as data. In particular, we selected the AUSFTA, KORUS, and TPP to assess the progress and evolution in international agreements and investigate the existing relevant content on the pricing and reimbursement of newly marketed medicines. Results Similar to the provisions for intellectual property, the scope of international agreements regarding pricing and reimbursement decisions are broadened and strengthened. Over time, the domain of transparency, re-naming procedural fairness, has changed significantly more than the remaining domains. Pharmaceutical companies will have more opportunities to advocate for their positions, to protect their interests in decision processes, to investigate the decisions on listings and setting the amounts of reimbursement, and to challenge these decisions. Conclusions Recently signed international agreements favor companies over governments with underscoring procedural fairness and timely access. However, access to affordable medicines is the goal towards which international agreements should aim. In a similar vein, substantial fairness and the accountability of companies should be discussed when negotiating agreements or adopting international agreements through domestic legislation.

Abstract Background Although the association between the price of generic drugs and market competitiveness has been explored in various high-income countries, this association has not been empirically evaluated in South Korea. We aim to determine the association between the prices of generic drugs and market competitiveness in South Korea. Methods A list of originator drugs approved by the national authority from 2000 to 2019 and their corresponding generic drugs were grouped along with the baseline information. The market was categorized into four groups based on the number of manufacturers: duopoly (2 manufacturers); low- (3–25 manufacturers); medium- (26–75 manufacturers); and high-competition (more than 76 manufacturers) markets. Price variance, calculated as the difference between the maximum price and minimum price divided by the maximum price, was obtained. A multivariate regression model was applied to regress price variance on the characteristics of market competitiveness, controlling for the characteristics of the originator drugs and their price level in the market. Results A total of 986 originator drugs were identified and then divided into duopoly (31%), low- (56%), medium- (9%), and high-competition (4%) markets; the median of the price variance for these markets was 0.013, 0.077, 0.200, and 0.228, respectively. In a multivariate regression model, price variance was associated with the characteristics of the originator drug, including the Anatomical Therapeutic Chemical classification, the route of administration, and the approval year. Controlling for the characteristics of the originator drugs, market competitiveness was positively associated with price variance. Conclusions The positive association between price variance and market competitiveness is still consistent in South Korea, where rare price competition among a large number of generic manufacturers has been reported. However, no significant price variance was observed between medium- and high-competition markets. These findings support policies for managing a large number of generic manufacturers in South Korea.

Abstract Background Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea. Methods We conducted a retrospective cohort study using Korea’s National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis. Results During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p

Regulatory decisions for new drugs approval present high uncertainty, low reversibility, the avoidance of observable errors, and high political stakes. However, research on the behavior of regulatory agencies is scarce, particularly in the context of more open decision-making processes. We aimed to evaluate the perceptions of regulatory decision-making for new drugs approval from the viewpoints of the manufacturers in South Korea. In 2019, employees in domestic (n = 5) and foreign (n = 7) manufacturers with expertise in regulatory affairs were invited to participate in a questionnaire survey and semi-structured group interview. We asked about the relevance of various criteria in regulatory decision-making, the participation of various stakeholders, and the degree of consent for new drug approval with uncertainty. The domestic and foreign manufacturers perceived that a regulatory decision made by the MFDS was solely based on technical merit within a closed decision-making system. They responded that safety, efficacy, and benefit-to-harm ratio were the most relevant criteria and the most prioritized criteria in regulatory decision-making. They also perceived that the MFDS was the sole relevant member in a regulatory decision. However, the foreign manufacturers disagreed that the regulatory agency and the advisory committee were independent of conflicts of interest, which might imply that regulatory decisions were occasionally determined by the agency given the political benefits and/or costs within a more open system. The role of an advisory committee in terms of deliberation and participatory democracy were requested to make politically legitimate regulatory decisions from the viewpoints of the manufacturers. However, their perceptions toward public involvement in regulatory decision-making is still at the early stage.

In the early SARS-CoV-2 (COVID-19) pandemic, four major vaccines were approved despite limited efficacy and safety data through short regulatory review periods. Thus, it is necessary to assess the benefit-risk (BR) profiles of the COVID-19 vaccines. We conducted a quantitative BR assessment for four COVID-19 vaccines (mRNA-based: mRNA-1273 and BNT162b2; viral vector-based: Ad26.COV.2 and ChAdOx1-S) using multi-criteria decision analysis. Three benefit criteria and two risk criteria were considered: preventing COVID-19 infection for (1) adults aged ≥18 years; (2) seniors aged 60 years or older; and (3) severe COVID-19, adverse events (AEs), and serious AEs. Data were retrieved from clinical trials, observational studies, and county-specific AE monitoring reports. Based on the collected data, vaccines were scored for each criterion. 22 professionals weighted each criterion. The overall BR score was calculated using scores and weights. mRNA-1273 was the most preferred vaccine in pre-authorization and BNT162b2 in post-authorization. We found that the mRNA vaccine had a good balance between the benefits and risks. Using this BR assessment, the benefit-risk profile of COVID-19 vaccines can be updated with cumulated data. It will contribute to building evidence for decision making by policy makers and health professionals.

Abstract Background Previous studies have classified cameramen’s job as physiologically heavy work and identified the risk factors of work-related musculoskeletal disorders (WRMDs) in cameramen. However, those studies limited their research subjects to cameramen. In this study, we compared the frequency and severity of WRMDs between cameramen and office workers. Methods A total of 293 subjects working in four broadcasting companies in Korea were recruited. A questionnaire survey was conducted for a month, starting in October 2016. The subjects were divided into cameramen and office workers according to their occupation. We compared the frequency and severity of WRMDs and ergonomic risk assessment results between the two groups. Results The high-risk WRMD group had a higher proportion of cameramen than office workers. Moreover, the high ergonomic risk group also had a higher proportion of cameramen than office workers for WRMDs in the upper extremities and waist+lower extremities. In the multivariable-adjusted model comparing cameramen and office workers, the odds ratio (OR) with 95% confidence interval (95% CI) for high-risk WRMDs was 3.50 (95% CI: 1.92–7.72) for the upper extremities and 3.18 (95% CI: 1.62–6.21) for the waist and the lower extremities. The ORs by body parts were 3.11 (95% CI: 1.28–7.57) for the neck, 3.90 (95% CI: 1.79–8.47) for the shoulders, and 4.23 (95% CI: 1.04–17.18) for the legs and feet. Conclusions Our study suggests that cameramen are at high risk of WRMDs. Workplace improvements and management of the neck, shoulders, and lower extremities, which are susceptible to WRMDs, are necessary to prevent musculoskeletal disorders among cameramen.