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Abstract Background Since the influx of international immigrants to South Korea (Korea) in the 1980s, the number of immigrants married to native Koreans has increased substantially over the last 30 years. This study aims to provide recent evidence on the self-rated health of immigrant women married to native men and raising children. We evaluated the self-rated health of immigrant women sorted by their country of origin and elucidated factors that affect their self-rated health. Methods Data were obtained from the 2015 Korean National Multi-Cultural Family Survey. From the survey, a total of 6960 Korean-Chinese, Han-Chinese, Japanese, Vietnamese, and Filipino women were identified and a series of logistic regressions was conducted to elucidate factors that affected the self-rated health of immigrant women. Results The majority of immigrant women in Korea perceived that they are healthy. However, the self-rated health of immigrant women varied by country of origin. Korean-Chinese and Japanese immigrants are less likely to perceive that they are healthy compared with Filipino and Vietnamese immigrants. We identified several factors at the individual, household, and community levels and found that the majority of them are likely to be ethnic dependent. However, satisfaction with husband and experience of unmet medical needs presented consistent results in the five ethnicity groups. Conclusions Programs that strengthen spousal relationships and policies to enhance access to healthcare could be prioritized options to improve the self-rated health of immigrant women in Korea.

Histatin peptides are endogenous anti-microbial peptides that were originally discovered in the saliva. Aside from their broad anti-microbial properties, these peptides play an important role in multiple biological systems. Different members of this family are thought to have relative specializations, with histatin-5 originally being thought to have mostly anti-fungal properties, and histatin-1 having strong wound healing properties. In this report, we describe the robust wound healing properties of histatin-5 and elucidate a functional domain, which is necessary and sufficient for promoting wound healing. We demonstrate these findings in multiple different cell types in vitro and with a standardized murine corneal wound healing model. Discovery of this wound healing domain and description of this functional role of histatin-5 will support developing therapies.

Abstract Background The speed of adoption of new drugs and frequencies of substitutions leads to changes in health care expenditures as well as patient outcomes. In this study, we aim to understand the speed of adoption of new drugs and their prescription volume in health care institutions and evaluate the impact of policy options to manage pharmaceutical expenditure. Methods We conducted a retrospective cohort study of health care institutions prescribing NOACs, including Apixaban, Dabigatran, and Rivaroxaban, to address the speed of adoption and their substitution from October 1, 2010, through December 31, 2015, using the National Health Insurance Service-National Sample Cohort. Two threshold time points, including the extension of reimbursement with the need for the letter of opinion and the withdrawal of the letter of opinion, were noted in this study. Then, we applied a survival analysis to elucidate factors that affected the speed of adoption of NOACs, and interrupted time series analysis to estimate the effect of amendments in reimbursement coverage in prescription volume. Results Among 934 health care institutions in a study population, 334 institutions (36%) had prescribed NOACs at least one time during the study period, indicating that health care institutions were conservative in adopting new drugs. However, the speed of adoption was related to the characteristics of health care institution. We also found that prescriptions of NOACs before the withdrawal of the need for the letter of opinion were marginal, and the prescription volume of NOACs was significantly increased after the withdrawal of a letter of opinion. Conclusions Health care institutions were conservative in adopting new drugs, and the speed of adoption is not closely related to an increased prescription volume in the short run. Thus, policies that are centered on managing pharmaceutical expenditure should be devised with considering the impact of introducing new drugs in the long run. A letter of opinion, which was devised to manage prescriptions of NOACs, was effective in managing pharmaceutical expenditures in health care institutions, particularly for tertiary institutions. Conversely, the withdrawal of the need for the letter of opinion should be implemented with caution.

Objective: Although quarantine is an effective measure for the prevention of the spread of infectious diseases, it may have negative effects on the mental health of the isolated individual. During the 2015 outbreak of the Middle East Respiratory Syndrome (MERS) in Korea, healthcare workers came in contact with patients with MERS were quarantined either at home or in a hospital ward. In this study, we aimed to compare the psychiatric symptoms of these employees according to the method of quarantine.Methods: All 146 quarantined staff completed self-report questionnaires. Depressive symptoms were measured using the Patient Health Questionnaire-9, anxiety symptoms were assessed using Spielberger's State-Trait Anxiety Inventory, and acute stress disorder (ASD) symptoms were evaluated using the Stanford Acute Stress Reaction Questionnaire.Results: The in-hospital quarantine group had a higher rate of symptoms of depression (p < 0.001) and ASD (p = 0.014) than the group quarantined at home. Logistic regression analysis showed that respondents quarantined in the hospital (OR = 6.342; 95% CI 1.853–21.708) and those quarantined for longer periods (OR = 1.153, 95% CI = 1.036–1.285) had a higher risk of depressive symptoms.Conclusions: In-hospital quarantine and quarantine for longer periods increase the risk of depressive symptoms. When quarantine measures are taken, certain measures are needed to minimize the risk of psychiatric problems. Appropriate interventions should be implemented if psychiatric problems occur.

Abstract Background Recently, interest in compulsory licensing of pharmaceuticals has been growing regardless of a country’s income- level. We aim to investigate the use of compulsory licensing as a legitimate part of the patent system and tool for the government to utilize by demonstrating that countries with a mature patent system were more likely to utilize compulsory licensing of pharmaceuticals. Methods We used a multivariate logistic model to regress attempts to issue compulsory licensing on the characteristics of the intellectual property system, controlling for macro context variables and other explanatory variables at a country level. Results A total 139 countries, selected from members of the World Trade Organization, were divided into a CL-attempted group (N = 24) and a non-CL-attempted group (N = 115). An attempt to issue compulsory licensing was associated with population (+) and a dummy variable for other regions, including Europe and North America (−). After controlling for macro context variables, mature intellectual property system was positively associated with attempting compulsory licensing. Conclusions Our study provided evidence of an association between attempting compulsory licensing and matured patent systems. This finding contradicts our current understanding of compulsory licensing, such as compulsory licensing as a measure to usurp traditional patent systems and sometimes diametrically opposed to the patent system. The findings also suggest a new role of compulsory licensing in current patent systems: compulsory licensing could be a potential alternative or complement to achieve access to medicines in health systems through manufacturing and exporting patented pharmaceuticals.

Introduction: Generic entry is a well-known driver of competition and cost containment.Objectives: We aim to measure the market exclusivity of originator drugs and to determine what influences the entry of generics in South Korea.Methods: A list of originator drugs approved by the authority from 2000 to 2013 and their corresponding generics were paired. An event history model was applied for a statistical estimation for the duration until generic entry and to identify abbreviating or prolonging factors on the duration.Results: A total of 2,061 pairs of originator and generics were identified. The market exclusivity for the originator drugs, including NDAs and non-NDAs, has not notably changed. However, competition among non-NDAs was less common than we expected. We found delayed time to entry of generics in the long run, particularly for non-NDAs in injection forms and biologics, and this finding is partially associated with market attractiveness.Conclusion: The authority should address the delayed availability of certain types of generic drugs. The government could provide information on off-patent pharmaceuticals with no generic competition, designate their corresponding submissions as prioritized in the review process, and provide additional market exclusivity when entering the market via a long period of exclusivity.

IntroductionSodium hyaluronate eye drops are frequently prescribed for dry eye disease in South Korea.ObjectivesThis study analyzed the trends in the utilization of sodium hyaluronate eye drops and evaluate the impact of the introduction of high-priced disposable forms in the South Korean market.MethodsThe yearly claims data for sodium hyaluronate eye drops from 2002 to 2015 were retrieved from the National Health Insurance Service-National Sample Cohort. Prescriptions of sodium hyaluronate eye drops were sorted by the characteristics of patients and health care institutions.ResultsThe number of prescriptions has continuously increased and the share of disposable forms in total prescriptions reached 37% in 2015. Particularly, the prevalence of prescriptions (general users) has increased during the study period from 2,562/100,000 persons in 2002 to 14,732/100,000 persons in 2015, while the incidence of prescriptions (new users) has remained steady during the study period, approximately 3,500/100,000 persons. More female patients were noted in terms of general users and new users, and the proportion of male patients was higher in new users than in general users. The average age of general users increased during the study period, while that of new users slightly decreased. Finally, the distribution of prescription category was significantly different between sex and age groups in frequently prescribed users.ConclusionsEye drops in disposable forms, which are safe and more convenient to use, have expanded the market in South Korea and caused equity issues in utilization. Thus, the utilization of eye drops should be closely monitored from the perspectives health equity.

IntroductionUnderstanding marketing strategies and price competition among manufacturers is essential to manage health care expenditures, particularly those related to blockbuster drugs.ObjectivesTo assess marketing and pricing strategies of blockbuster drugs in South Korea.MethodsBaseline information on manufacturers who were granted marketing approval for choline alfoscerate in various forms was retrieved. Accumulation of manufacturers in the market was also identified, and manufacturers were categorized into first movers and latecomers based on their marketing time. Then, an event history analysis and a regression analysis were applied to estimate the duration of marketing and their price competition.ResultsCurrently, 109, 83, and 26 manufacturers produce choline alfoscerate in capsule, tablet, or syrup form, respectively, indicating that many manufacturers have marketed generics and the majority of the generics are categorized as latecomers. The size of the manufacturer was a significant factor in marketing new medicines, while the variable was not related to the marketing of modified drugs. Furthermore, price competition in the market was rare and only a few major firms initiated price competition.ConclusionThe Korean market appears to be an example of perfect competition when we focus on the number of manufacturers. However, the market is near-monopolistic when examining the price of generic drugs. While product competition between different forms of drugs is effective in lowering price, product competition within the same form of a drug does not exist in the market.

Light detection and ranging (LiDAR) data of 3D point clouds acquired from laser sensors is a crucial form of geospatial data for recognition of complex objects since LiDAR data provides geometric information in terms of 3D coordinates with additional attributes such as intensity and multiple returns. In this paper, we focused on utilizing multiple returns in the training data for semantic segmentation, in particular building extraction using PointNet++. PointNet++ is known as one of the efficient and robust deep learning (DL) models for processing 3D point clouds. On most building boundaries, two returns of the laser pulse occur. The experimental results demonstrated that the proposed approach could improve building extraction by adding two returns to the training datasets. Specifically, the recall value of the predicted building boundaries for the test data was improved from 0.7417 to 0.7948 for the best case. However, no significant improvement was achieved for the new data because the new data had relatively lower point density compared to the training and test data.

Abstract Background Regulatory approval and reimbursement decisions are necessary if new drugs are to become accessible in a timely manner. However, the process of regulatory approval and the establishment of reimbursement decisions varies across countries. This study aims to analyze the duration between regulatory approval and reimbursement decision for new drugs and to evaluate various factors affecting the timely availability of new medicines in the Korean market. The duration was subdivided into regulatory approval–reimbursement application and reimbursement application–reimbursement decision. We used pharmaceutical approval data to identify new medicines, retrieved documents from the pharmaceutical benefits committee to collect information on reimbursement decision, and applied a non-parametric event history model. Results A total of 128 new medicines applied for reimbursement decision, including 85 drugs between 2007 and 2013 and 43 drugs between 2014 and 2016. Delays in access to new medicines occurred at various levels, and various factors affected in different durations. In proportional hazard model, the second period shortened all durations in the models. Biologics and clinically improved drugs were the factor that delayed the duration of regulatory approval–reimbursement application, while uncertain drugs in clinical effectiveness and ATC J or L delayed the duration of reimbursement application–reimbursement decision. Conclusions The duration between regulatory approval and reimbursement decision has decreased, and the main cause of the delay has changed. For instance, the proportion of reimbursement trial–reimbursement decision in the total duration was 62.9% (18.39 months out of 29.24 months) in the first period, while the proportion of regulatory approval–reimbursement trial in the total duration was 64.2% (8.6 months out of 13.40 months) in the second period. A series of policies to reinforce access to medicines after 2014 has been effective for the timely availability of new medicines, including both prompt reimbursement application decided by manufacturers and timely review process by the authorities.

Abstract Background The inclusion of patent linkage mechanisms in bilateral and plurilateral trade and investment agreements has emerged as a key element in the United States’ TRIPS-Plus intellectual property (IP) negotiating agenda. However, the provisions establishing patent linkage mechanisms in several agreements appear to reflect a degree of ambiguity, potentially enabling some flexibility in their implementation. In this study, we reviewed the features of the prototypic patent linkage mechanism established by the Hatch-Waxman Act in the United States, and compared these with the implementation of systems in three countries whose agreements with the US include patent linkage obligations. From these analyses, we draw lessons for moderating the impact of these mechanisms on access to generic medicines. Methods We reviewed the features of the patent linkage mechanism in the US, and undertook a detailed analysis of relevant treaty provisions and the manner of implementation in Canada, Australia, and South Korea. Results A key difference between the US implementation of patent linkage and that of its trading partners is the disparate treatment afforded to biologics. Because of the significant differences in the regulatory frameworks applying to small molecule and biologic medicines in the US, the Hatch- Waxman provisions do not apply to biologics and they are not subject to patent linkage. By contrast, the regulatory frameworks in Canada, Australia and South Korea do not reflect similar distinctions and thus patent linkage mechanisms also capture biologics. Additional variations in implementation, mainly the result of constructive ambiguities in the respective treaty texts, offer potential opportunity for mitigating the adverse impact of patent linkage provisions on market entry of generic medicines. Practical measures include ensuring the availability of an accessible, transparent and easily searchable database of patent information; avoiding automatic stays of generic marketing approval where possible; and requiring certification by rights holders to prevent abuse of the system. Conclusions Where countries accept treaty obligations to establish patent linkage mechanisms, the impact on access to generic medicines may be moderated to a degree by retaining and exploiting constructive ambiguities in the treaty text and addressing practical aspects of implementation.

Abstract Background Subsyndromal delirium, a condition in which patients exhibit some, but not all, of the symptoms of delirium, can negatively affect the outcomes of patients with cancer. However, the incidence of subsyndromal delirium in patients with gastric cancer is unknown. Here, we investigated the incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer. Methods We recruited consecutive patients with gastric cancer who were scheduled for curative resection at a tertiary hospital. Patients’ subsyndromal delirium symptoms were serially assessed preoperatively and 1, 2, 3, and 7 days postoperatively using the Delirium Rating Scale-Revised-98 (DRS-R-98). A DRS-R-98 score of 8–14 at any postoperative assessment was considered to indicate subsyndromal delirium. Sociodemographic and pre−/intra-operative clinical data were also assessed. Logistic regression analyses were used to determine the associated risk factors. Results Data were analysed from 163 out of 217 eligible patients. Postoperative delirium occurred in one patient (0.6%) and subsyndromal delirium occurred in 19 patients (11.7%). Age ≥ 70 years (odds ratio, [OR] 3.85; 95% confidence interval [CI], 1.36–10.92; p = 0.011) and education level ≤ 9 years (OR, 3.98; 95% CI, 1.39–11.41; p = 0.010) were independent risk factors of subsyndromal delirium after adjusting for preoperative cognitive function. Other pre−/intra-operative variables including anxiety/depression, poor sleep quality, and anaesthesia duration were not associated with subsyndromal delirium. Conclusions In contrast to the low incidence of delirium among patients undergoing curative resection of gastric cancer, a substantial proportion of such patients experienced subsyndromal delirium. Considering the prognostic implications, more careful detection and management of subsyndromal delirium may be warranted in patients with gastric cancer.

Background Trap-door deformity is a biophysical phenomenon in which U-, C-, or V-shaped linear scars tend to become depressed and the tissue circumscribed by them tends to bulge. The aim of the present study was to demonstrate the efficacy of triamcinolone acetonide (TCA) injection and subcision as a first-line treatment for post-traumatic acute trap-door deformity. Methods In trap-door deformity patients, a subcision was made by cutting the fibrotic band along the scar line in the depression using a 22-gauge needle. TCA was administered. An intralesional injection was made along areas of scarring that were difficult to penetrate with the needle. Scar quality parameters were assessed at each follow-up by a single observer and the patient, using the patient and observer scar assessment scale (POSAS) with an additional question about bulging. Results The average POSAS score per question on the observer scale improved from 6.6±1.31 to 3.6±1.08, and the average POSAS score per question on the patient scale improved from 5.5±1.57 to 2.5±1.26. The average bulging score on the observer scale decreased from 6.0±0.98 to 3.0±0.83, and that on the patient scale decreased from 5.0±1.67 to 2.0±1.30. The average general opinion score on the observer scale decreased from 5.5±1.12 to 3.5±0.91, and that on the patient scale decreased from 6.0±1.84 to 2.0±0.79. Conclusions Better outcomes can be obtained by using both TCA and subcision as the first-line therapy for post-traumatic acute trap-door deformity.

Abstract Background Precise assessment of health-related quality of life (HRQOL) with a reliable and valid measure is a prerequisite to the enhancement of HRQOL. This study examined the psychometric properties of the Korean version of the Medical Outcomes Study HIV Health Survey (K-MOS-HIV). Methods The reliability and validity of the K-MOS-HIV were examined in a multicenter survey involving 201 outpatients with human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) from four teaching hospitals throughout Korea. Results Ceiling effects were observed in six subscales scores, particularly, for the role functioning (71.1%), social functioning (63.2%), and pain (48.8%) scores. The Cronbach’s α for the physical health summary and mental health summary were 0.90 and 0.94, respectively, and it ranged from 0.78 to 0.95 for the subscales. The results of the exploratory structural equation modeling supported the two-factor structure of the K-MOS-HIV (physical health summary and mental health summary). An examination of the mean square statistics values from the Rasch analysis showed that the information-weighted fit and outlier-sensitive fit statistics were within the acceptable ranges of 0.6–1.4 except for two items in the mental health summary. The convergent validity of the K-MOS-HIV was supported by its significant positive correlations with the World Health Organization Quality of Life-HIV-BREF subscale scores. Its known-group validity was proven with its ability to detect significant differences in several K-MOS-HIV subscale scores among participants with different sociodemographic and clinical characteristics. Conclusions The K-MOS-HIV health survey appears to be a reliable and valid measure of HRQOL.

The article discusses the study of the electrothermal soft manipulator enabling safe transport and handling of thin cell/tissue sheets and bioelectronic devices. Topics discusses include this study presents a soft manipulator that can manipulate and transport cell/tissue sheets and ultrathin wearable biosensing devices seamlessly; and the soft manipulator consists of an ultrafast thermo-responsive, microchanneled hydrogel layer with tissue-like softness and an electric heater layer.

The title compound, C12H11N5, was synthesized as a potential tridentate ligand to make catalytic metal complexes. The dihedral angle between the pyrazolyl rings is 67.9 (1)°. The most prominent feature in the crystal packing are C—H...N hydrogen-bonding interactions that link the molecules into a supramolecular tape along the b-axis direction.

In the title complex, [CoCl2(C25H21N5)], the CoII atom is coordinated by two Cl atoms and two N atoms, provided by a tridentate pyrazolylpyridyl ligand, forming a slightly distorted tetrahedral geometry [range of angles: 96.51 (10) (chelate ring) to 118.60 (9)°]. The dihedral angle between Cl/Co/Cl and N/Co/N planes is 86.83 (7)°. The chelate ring has the conformation of a distorted boat. The dihedral angle between pyridyl ring and the coordinated pyrazolyl ring is 56.16 (12)°. The uncoordinated pyrazolyl ring is almost perpendicular to the pyridyl ring with the dihedral angle of 87.49 (10)°. In the crystal packing, intermolecular phenyl-C—H ...π(pyridyl) interactions generate dimeric aggregates. These are connected into a zigzag supramolecular chain along the c-axis direction via π–π interactions [inter-centroid distance between pyridyl and phenyl rings = 3.664 (2) Å].

In the title compound, C13H13N5, the planes of the pyrazolyl groups are nearly perpendicular to that of the central pyridine ring, making dihedral angles of 87.77 (8) and 85.73 (7)°. In the crystal, weak C—H...N hydrogen bonds link the molecules into layers extending parallel to (10-1).

In the complex cation of the title salt, [CrCl(C2H6OS)5]Cl2, the CrIII ion is coordinated by one chloride ligand and five O atoms from dimethyl sulfoxide (DMSO) ligands, leading to a slightly distorted octahedral coordination environment [O—Cr—O angles range from 86.69 (16) to 92.87 (16)°]. In the crystal, complex cations are arranged in hexagonally packed rows parallel to [010], with the chloride counter-anions situated in between. The interactions between cations and anions are mainly ionic in nature.