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Background: Influenza's potential impact on active tuberculosis (TB) development has been debated, with limited clinical evidence. To address this, we explored the association between influenza episodes and TB incidence in a national cohort of individuals with latent TB infection (LTBI). Methods: We examined adults (≥20 years) diagnosed with LTBI between 2015 and 2020, using the Health Insurance Review and Assessment Service's national database in South Korea. We collected demographic data, comorbidities, and influenza episodes within 6 months before and after the initial LTBI diagnosis (prior vs. subsequent episode). We stratified the analysis into groups with and without TB preventive therapy (TPT). Results: Among 220,483 LTBI subjects, 49% received TPT, while 51% did not. The average age was 48.4 years, with 52% having comorbidities. A prior and subsequent influenza episode was identified in 3221 and 4580 individuals, respectively. Of these, 1159 (0.53%) developed incident TB over an average follow-up of 1.86 years. The incidence rates of TB were comparable between individuals with and without prior and/or subsequent influenza episodes in the TPT group, but 1.4 times higher in the non-TPT group for those with such episodes. Cox proportional-hazards regression analysis indicated that influenza was not a risk factor for incident TB in the TPT group. However, a subsequent influenza episode significantly increased TB risk in the non-TPT group (hazard ratio: 1.648 [95% CI, 1.053–2.580]). Conclusions: In individuals with LTBI not receiving TPT, experiencing an influenza episode may elevate the risk of developing active TB.

BackgroundInformation and communications technology–based tailored management (TM) intervention is a novel automatic system in which a smartphone app for the management of patients with hypertension and diabetes, the provider web, and Bluetooth devices are linked. However, little evidence exists regarding the cost-effectiveness of the interventions using mobile apps. ObjectiveThis study aimed to assess the cost-effectiveness of TM intervention for adult patients with hypertension or diabetes in primary care compared with usual care (UC). MethodsCost-effectiveness analysis using a Markov model was conducted from the Korean health care system perspective. Based on 6-month outcome data from an information and communications technology–based tailored chronic disease management (ICT-CM) trial, effectiveness over a lifetime beyond the trial periods was extrapolated using a cardiovascular disease risk prediction model. Costs were estimated using ICT-CM trial data and national health insurance claims data. Health utility weights were obtained from the Korea National Health and Nutrition Examination Survey. ResultsIn the base-case analysis, compared with UC, TM was more costly (US $23,157 for TM vs US $22,391 for UC) and more effective (12.006 quality-adjusted life-years [QALYs] for TM vs 11.868 QALYs for UC). The incremental cost-effectiveness ratio was US $5556 per QALY gained. Probabilistic sensitivity analysis showed that the probability of TM being cost-effective compared with UC was approximately 97% at an incremental cost-effectiveness ratio threshold of US $26,515 (KRW 35 million) per QALY gained. ConclusionsCompared with UC, TM intervention is a cost-effective option for patients with hypertension or diabetes in primary care settings. The study results can assist policy makers in making evidence-based decisions when implementing accessible chronic disease management services.

Cancer cells mechanically interact with the tumor microenvironment during cancer development. Mechano-reciprocity has emerged as a crucial factor affecting anti-cancer drug resistance during adjuvant therapy. Here, we investigated the focal adhesion kinase (FAK)/Yes-associated protein (YAP) signaling axis as a prospective strategy for circumventing cisplatin resistance in ovarian cancer (OC). The Cancer Genome Atlas (TCGA) data analysis revealed that FAK overexpression significantly correlated with unfavorable clinical outcomes in patients with ovarian cancer. AFM indentation experiments showed that cell elasticity depends on FAK activity. Notably, the combination of FAK inhibition and cisplatin treatment led to a 69 % reduction in the IC50 of cisplatin. This combined treatment also increased apoptosis compared to the individual treatments, along with the upregulation of the pro-apoptotic factor BAX and cleaved PARP. Suppressing FAK expression sequestered YAP in the cytosol, potentially reducing cellular proliferation and promoting apoptosis. Moreover, reduced FAK expression sensitized drug-resistant OC cells to cisplatin treatment owing to a decrease in nuclear tension, allowing the relocation of YAP to the cytosol. In a mouse model, the co-administration of an FAK inhibitor and cisplatin significantly suppressed tumor growth and increased apoptotic events and DNA fragmentation. Our findings suggest that drug resistance can be attributed to the perturbation of mechanosensing signaling pathways, which drive the mechanical reinforcement of cancer cells. OC cells can restore their sensitivity to cisplatin treatment by strategically reducing YAP localization in the nucleus through FAK downregulation.

Objectives This study aimed to evaluate the risk of tuberculosis associated with the use of Janus kinase (JAK) inhibitors or biological disease-modifying antirheumatic drugs (bDMARDs) in patients diagnosed with rheumatoid arthritis (RA) in South Korea.Methods In this nationwide matched-cohort study, we retrospectively identified adult patients with new-onset RA from the National Health Insurance Service database who were prescribed bDMARDs or JAK inhibitors and recently underwent latent tuberculosis infection (LTBI) screening during 2012‒2021, and followed them up until the end of 2022 for the development of active tuberculosis. HRs were estimated using Cox proportional hazards regression in a propensity score-matched cohort.Results Among 16 760 matched patients with RA (3352 JAK inhibitor users and 13 408 bDMARD users), 18.8% received tuberculosis preventive therapy for LTBI. Overall, JAK inhibitor users had a significantly lower risk of tuberculosis than bDMARD users (HR (95% CI)=0.37 (0.22 to 0.62)). Among the patients treated for LTBI, patients with low treatment adherence had a significantly higher risk than those without LTBI (HR (95% CI)=2.78 (1.74 to 4.44)). Patients without LTBI and using JAK inhibitors had a significantly lower risk of tuberculosis across all ages and sexes compared with bDMARD users.Conclusion Patients with RA using JAK inhibitors have a significantly lower risk of active tuberculosis than bDMARD users in South Korea; however, patients with RA having LTBI are equally at risk regardless of the treatment received (JAK inhibitor vs bDMARD). Therefore, vigilant tuberculosis monitoring, especially in patients with low adherence to tuberculosis preventive therapy, is essential.

Objectives: Limited evidence exists regarding the impact of adherence to diverse tuberculosis (TB) preventive therapy (TPT) regimens on TB risk in individuals with TB infections (TBIs). This study aimed to examine the association between adherence to three TPT regimens and TB incidence. Methods: This population-based retrospective cohort study used South Korean national health insurance data to identify individuals who were newly diagnosed with TBI between 2015 and 2020. TB incidence was compared among the different TPT regimens used. Treatment adherence was evaluated using the medication possession ratio (MPR). Results: The study involved 220,483 individuals with TBI, with half undergoing TPT. Over a mean 3.17-year follow-up, 2,430 cases of active TB were observed. TPT was associated with a 14% reduction in TB incidence risk in the entire study population with varying levels of TB risk. Non-adherence (MPR

Abstract Background Although gastric cancer patients generally experience drastic weight decrease post‐gastrectomy, the impact of weight decrease on type 2 diabetes risk remains unclear. We investigated the type 2 diabetes risk after gastric cancer surgery according to postoperative weight decrease in gastric cancer survivors in South Korea, the country with the world's highest rate of gastric cancer survival. Methods This retrospective nationwide cohort study included gastric cancer surgery recipients between 2004 and 2014 who survived for ≥5 years post‐surgery. We included patients without a history of diabetes at the time of surgery and those who had not received adjuvant chemotherapy before or after the surgery. Postoperative weight loss was defined as the per cent body weight loss at 3 years post‐surgery compared with the baseline. The type 2 diabetes risk was evaluated using Cox regression analyses for five groups of postoperative weight decrease. Results In 5618 included gastric cancer surgery recipients (mean age, 55.7 [standard deviation, SD, 10.9] years; 21.9% female; mean body mass index, 23.7 [SD, 2.9] kg/m2), 331 patients (5.9%) developed postoperative type 2 diabetes during follow‐up duration of 8.1 years (median; interquartile range, 4.8 years; maximum, 15.2 years). Compared with those who gained weight post‐surgery, patients with ≥ −15% to

Background This study aimed to compare the performance of established cardiovascular risk algorithms in Korean patients with new‐onset rheumatoid arthritis. Methods and Results This retrospective cohort study identified patients newly diagnosed with rheumatoid arthritis without a history of cardiovascular diseases between 2013 and 2019 using the National Health Insurance Service database. The cohort was followed up until 2020 for the development of the first major adverse cardiovascular event. General cardiovascular risk prediction algorithms, such as the systematic coronary risk evaluation model, the Korean risk prediction model for atherosclerotic cardiovascular diseases, the American College of Cardiology/American Heart Association pooled equations, and the Framingham Risk Score, were used. The discrimination and calibration of cardiovascular risk prediction models were evaluated. Hazard ratios were estimated using Cox proportional hazards regression. A total of 611 patients among 24 889 patients experienced a major adverse cardiovascular event during follow‐up. The median 10‐year atherosclerotic cardiovascular diseases risk score was significantly higher in patients with major adverse cardiovascular events than those without. The C‐statistics of risk algorithms ranged between 0.72 and 0.74. Compared with the low‐risk group, the actual risk of developing major adverse cardiovascular events increased significantly in the intermediate‐ and high‐risk groups for all algorithms. However, the risk predictions calculated from all algorithms overestimated the observed cardiovascular risk in the middle to high deciles, and only the systematic coronary risk evaluation algorithm showed comparable observed and predicted event rates in the low‐intermediate deciles with the highest sensitivity. Conclusions The systematic coronary risk evaluation model algorithm and the general risk prediction models discriminated patients with rheumatoid arthritis appropriately. However, overestimation should be considered when applying the cardiovascular risk prediction model in Korean patients.

Objectives: Despite the ethnic differences in cardiovascular (CV) risks and recent increase in the prescription of Janus kinase (JAK) inhibitors, limited evidence is available for their CV outcomes in Asian patients with rheumatoid arthritis (RA). We aimed to compare the major adverse CV events (MACEs) of JAK inhibitors to those of biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with RA without baseline CV disease (CVD).Methods: In a nationwide retrospective cohort study, patients newly diagnosed with RA without a history of CVD between 2013 and 2018 were identified using the National Health Insurance Service database. The cohort was followed up until the end of 2019 for the development of MACEs. Hazard ratios (HRs) for MACEs such as myocardial infarction, stroke, coronary revascularization, or all-cause death, were estimated using Cox proportional hazard regression in a propensity score-matched cohort.Results: In total, 4,230 matched patients with RA were included (846 JAK inhibitor users and 3,384 bDMARD users). The crude incidence rate (95% confidence intervals, CI) per 100 patient-years for MACEs was 0.83 (0.31–1.81) and 0.74 (0.53–1.02) in the JAK inhibitor and bDMARD groups, respectively. The risk of MACEs was not significantly different between JAK inhibitor and bDMARD users with an adjusted HR (95% CI) of 1.28 (0.53–3.11). There were no significant differences in the risk of MACEs between JAK inhibitors and bDMARDs in each subgroup according to the types of bDMARDs, age, sex, Charlson comorbidity index score, and comorbidities.Conclusion: Compared to bDMARDs, JAK inhibitors were not associated with the occurrence of MACEs in Korean patients with RA without a history of CVD.

BackgroundDrug-induced suicide has been debated as a crucial issue in both clinical and public health research. Published research articles contain valuable data on the drugs associated with suicidal adverse events. An automated process that extracts such information and rapidly detects drugs related to suicide risk is essential but has not been well established. Moreover, few data sets are available for training and validating classification models on drug-induced suicide. ObjectiveThis study aimed to build a corpus of drug-suicide relations containing annotated entities for drugs, suicidal adverse events, and their relations. To confirm the effectiveness of the drug-suicide relation corpus, we evaluated the performance of a relation classification model using the corpus in conjunction with various embeddings. MethodsWe collected the abstracts and titles of research articles associated with drugs and suicide from PubMed and manually annotated them along with their relations at the sentence level (adverse drug events, treatment, suicide means, or miscellaneous). To reduce the manual annotation effort, we preliminarily selected sentences with a pretrained zero-shot classifier or sentences containing only drug and suicide keywords. We trained a relation classification model using various Bidirectional Encoder Representations from Transformer embeddings with the proposed corpus. We then compared the performances of the model with different Bidirectional Encoder Representations from Transformer–based embeddings and selected the most suitable embedding for our corpus. ResultsOur corpus comprised 11,894 sentences extracted from the titles and abstracts of the PubMed research articles. Each sentence was annotated with drug and suicide entities and the relationship between these 2 entities (adverse drug events, treatment, means, and miscellaneous). All of the tested relation classification models that were fine-tuned on the corpus accurately detected sentences of suicidal adverse events regardless of their pretrained type and data set properties. ConclusionsTo our knowledge, this is the first and most extensive corpus of drug-suicide relations.

BackgroundManaging hypertension (HT) and diabetes mellitus (DM) is crucial to preventing cardiovascular diseases. Few studies have investigated the incidence and risk of cardiovascular diseases or mortality in uncontrolled HT or DM in the Asian population. Epidemiological studies of cardiovascular disease should be conducted with continuous consideration of the changing disease risk profiles, lifestyles, and socioeconomic status over time. ObjectiveWe aimed to examine the association of uncontrolled HT or DM with the incidence of cardiovascular events or deaths from any cause. MethodsThis population-based retrospective study was conducted using data from the Korean National Health Insurance Service–National Health Screening Cohort, including patients aged 40-79 years who participated in national screening from 2002 to 2003 and were followed up until 2015. The health screening period from 2002 to 2013 was stratified into 6 index periods in 2-year cycles, and the follow-up period from 2004 to 2015 was stratified accordingly into 6 subsequent 2-year periods. The incidence rates and hazard ratio (HR) for major adverse cardiovascular events (MACE) and death from any cause were estimated according to HT or DM control status. Extended Cox models with time-dependent variables updated every 2 years, including sociodemographic characteristics, blood pressure (BP), fasting blood glucose (FBG), medication prescription, and adherence, were used. ResultsAmong the total cohort of 440,249 patients, 155,765 (35.38%) were in the uncontrolled HT or DM group. More than 60% of the patients with HT or DM who were prescribed medications did not achieve the target BP or FBG. The incidence of MACE was 10.8-15.5 and 9.6-13.3 per 1000 person-years in the uncontrolled DM and uncontrolled HT groups, respectively, and increased with age. In the uncontrolled HT and DM group, the incidence of MACE was high (15.2-17.5 per 1000 person-years) at a relatively young age and showed no age-related trend. Adjusted HR for MACE were 1.28 (95% CI 1.23-1.32) for the uncontrolled DM group, 1.32 (95% CI 1.29-1.35) for the uncontrolled HT group, and 1.54 (95% CI 1.47-1.60) for the uncontrolled HT and DM group. Adjusted HR for death from any cause were 1.05 (95% CI 1.01-1.10) for the uncontrolled DM group, 1.13 (95% CI 1.10-1.16) for the uncontrolled HT group, and 1.17 (95% CI 1.12-1.23) for the uncontrolled HT and DM group. ConclusionsThis up-to-date evidence of cardiovascular epidemiology in South Korea serves as the basis for planning public health policies to prevent cardiovascular diseases. The high uncontrolled rates of HT or DM, regardless of medication prescription, have led us to suggest the need for a novel system for effective BP or glycemic control, such as a community-wide management program using mobile health technology.

Objectives: We analyzed tuberculosis (TB)-related costs according to treatment adherence, as well as the association between treatment adherence, treatment outcomes, and costs related to drug-susceptible TB in South Korea.Methods: Patients who had newly treated TB in South Korea between 2006 and 2015 were selected from nationwide sample claims data and categorized into adherent and non-adherent groups using the proportion of days TB drugs covered. Patients were followed-up from the initiation of TB treatment. The mean five-year cumulative costs per patient were estimated according to adherence. Moreover, we evaluated the relative ratios to identify cost drivers such as adherence, treatment outcomes, and baseline characteristics using generalized linear models. Four treatment outcomes were included: treatment completion, loss to follow-up, death, and the initiation of multidrug-resistant TB treatment.Results: Out of the 3,799 new patients with TB, 2,662 were adherent, and 1,137 were non-adherent. Five years after initiating TB treatment, the mean TB-related costs were USD 2,270 and USD 2,694 in the adherent and non-adherent groups, respectively. The TB-related monthly cost per patient was also lower in the adherent than in the non-adherent (relative ratio = 0.89, 95% CI 0.92–0.98), while patients who were lost to follow-up spent more on TB-related costs (2.52, 2.24–2.83) compared to those who completed the treatment.Conclusion: Non-adherent patients with TB spend more on treatment costs while they have poorer outcomes compared to adherent patients with TB. Improving patient adherence may lead to effective treatment outcomes and reduce the economic burden of TB. Policymakers and providers should consider commitment programs to improve patient’s adherence.

Abstract Background It is essential to have information on the disease burden of lung cancer at an individual level throughout the life; however, few such results have been reported. Thus, this study aimed to assess the lifetime disease burden in patients with lung cancer by assessing various factors, such as survival, years of life lost (YLL) and medical expenditure in South Korea based on real-world data and extrapolation. Methods Newly diagnosed lung cancer patients (n = 2919) in 2004–2010 were selected and observed until the end of 2015 using nationwide reimbursement claim database. The patients were categorised into the Surgery group, Chemo and/or Radiotherapy group (CTx/RTx), and Surgery+CTx/RTx according to their treatment modality. Age- and sex-matched control subjects were selected from among general population using the life table. The survival and cost data after diagnosis were analysed by a semi-parametric method, the Kaplan–Meier analysis for the first 100 months and rolling extrapolation algorithm for 101–300 months. YLL were derived from the difference in survival between patients and controls. Results Lifetime estimates (standard error) were 4.5 (0.2) years for patients and 14.5 (0.1) years for controls and the derived YLL duration was 10.0 (0.2) years. Lifetime survival years showed the following trend: Surgery (14.2 years) > Surgery+CTx/RTx (8.5 years) > CTx/RTx group (3.0 years), and YLL were increased as lifetime survival years decreased (2.3, 8.7, 12.2 years, respectively). The mean lifetime medical cost was estimated at 30,857 USD/patient. Patients in the Surgery group paid higher treatment cost in first year after diagnosis, but the overall mean cost per year was lower at 4359 USD compared with 7075USD of Surgery+CTx/RTx or 7626USD of CTx/RTx group. Conclusions Lung cancer has resulted in about 10 years of life lost in overall patients. The losses were associated with treatment modality, and the results indicated that diagnosing lung cancer in patients with low stage disease eligible for surgery is beneficial for reducing disease burden in terms of survival and treatment cost per year throughout the life.

Summary: Background/Objective: The number of gastric cancer and type II diabetes mellitus is increasing in Korea. Metabolic surgery could be extended to gastric cancer patients with type II diabetes, especially those who are expected to achieve long-term survival. This study aimed to investigate change of diabetic status in patients undergoing long-limb Roux-en-Y bypass reconstruction compared with conventional Billroth II after curative gastrectomy. In total, 130 patients from five university hospital centers underwent long-limb Roux-en Y reconstruction after radical distal gastrectomy. Methods: In the long-limb group, the length of biliopancreatic limbs was more than 80 cm, and the length of the Roux limb was more than 80 cm. The control group comprised 96 patients who underwent conventional Billroth II reconstruction after distal gastrectomy. Follow-up data at three, six, nine, and 12 months were compared between the two groups. Results: Fasting blood sugar (FBS) and hemoglobin (Hb) A1c levels decreased more significantly in the long-limb Roux-en-Y group (FBS: 28.8 mg/dL; HbA1c: 0.72%). However, decreases in body mass index, albumin, and hemoglobin did not differ significantly between the two groups. Diabetes control significantly improved in the long-limb group. In multivariate analysis, long-limb bypass reconstruction was the significant factor for glycemic outcomes. Conclusion: Roux-en-Y bypass with increased length of limbs after gastrectomy shows a favorable glycemic control for gastric cancer patients with type II diabetes without nutritional deficit and anemia. To obtain future perspectives, large-scale prospective studies with long-term outcomes are needed. Keywords: Type II DM, Gastric cancer, Long limb Roux-en Y

BackgroundTramadol is known to cause fewer adverse events (AEs) than other opioids. However, recent research has raised concerns about various safety issues. ObjectiveWe aimed to explore these new AEs related to tramadol using social media and conventional pharmacovigilance data. MethodsThis study used 2 data sets, 1 from patients’ drug reviews on WebMD (January 2007 to January 2021) and 1 from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS; January 2016 to December 2020). We analyzed 2062 and 29,350 patient reports from WebMD and FAERS, respectively. Patient posts on WebMD were manually assigned the preferred terms of the Medical Dictionary for Regulatory Activities. To analyze AEs from FAERS, a disproportionality analysis was performed with 3 measures: proportional reporting ratio, reporting odds ratio, and information component. ResultsFrom the 869 AEs reported, we identified 125 new signals related to tramadol use not listed on the drug label that satisfied all 3 signal detection criteria. In addition, 20 serious AEs were selected from new signals. Among new serious AEs, vascular disorders had the largest signal detection criteria value. Based on the disproportionality analysis and patients’ symptom descriptions, tramadol-induced pain might also be an unexpected AE. ConclusionsThis study detected several novel signals related to tramadol use, suggesting newly identified possible AEs. Additionally, this study indicates that unexpected AEs can be detected using social media analysis alongside traditional pharmacovigilance data.

The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.

Abstract Background This study investigated the sex-specific incidence of asthma and the effects of modifiable risk factors, particularly obesity, on asthma incidence among middle-aged and older individuals in Korea. Methods We used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS), which includes health examinees aged 40–79 years in 2002–2003. In total, 459,529 participants with baseline anthropometric measurements were followed-up for 10 years and the development of asthma was evaluated (2004–2013). For subgroup analysis, 246,019 participants who had body mass index (BMI) and waist circumference (WC) measurements taken in 2008–2009 were included in the analysis of the asthma incidence for 2010–2013. Factors associated with asthma were analysed using Cox proportional hazard models. Results The cohort comprised 4,248,813 (men, 2,358,541; women, 1,890,272) person-years of follow-up for 2004–2013. The asthma incidence was 10.58 and 15.03 per 1000 person-years for men and women, respectively. Asthma incidence increased with age, notably so in men. Obesity based on the baseline BMI was significantly associated with asthma development in both sexes (men, HR = 1.23, 95% confidence interval (CI) = 1.13–1.34; women, HR = 1.40 95% CI = 1.32–1.48). High WC was also related to asthma incidence in both sexes with statistical significance (men, HR = 1.34, 95% CI = 1.16–1.57; women, HR = 1.19 95% CI = 1.03–1.37). Analysis of the combined effects of BMI and WC showed that men had a higher asthma risk in the group with both general obesity and abdominal obesity than in the group with non-abdominal obesity and normal BMI. However, obese women had a higher risk of asthma regardless of abdominal obesity. Similarly, smoking was associated with asthma in both sexes but drinking and physical activity showed different associations between the sexes. Conclusions Our results revealed that asthma incidence was substantially high at old age and lifestyle factors were associated with asthma development. Practical strategies including weight control and healthy lifestyle modification are required to prevent asthma in older people.

Background: Potential adverse effects might be caused by increasing the number of antipsychotic prescriptions. However, the empirical evidence regarding pediatric psychiatric patients is insufficient. Therefore, we explored the antipsychotic-induced adverse effects focusing on the neurological system.Method: Using the medical information of pediatric patients retrieved from the claims data of Health Insurance Review and Assessment in Korea, we identified those psychiatric patients who were started on antipsychotic treatment at age 2–18 years between 2010 and 2018 (n = 10,969). In this study, movement disorders and seizures were considered as major neurological adverse events. The extended Cox model with time-varying covariates was applied to explore the association between antipsychotic medication and adverse events.Findings: Total 1,894 and 1,267 cases of movement disorders and seizures occurred in 32,046 and 33,280 person-years, respectively. The hazard risks of neurological adverse events were 3–8 times higher in the exposed to antipsychotics period than in the non-exposure period. Among the exposure periods, the most dangerous period was within 30 days of cumulative exposure. High doses or polypharmacy of antipsychotics was associated with increased risks of neurological adverse events. Among individual antipsychotics, haloperidol showed the highest risk of developing movement disorders among the examined agents. Quetiapine showed a lower risk of developing movement disorders but a higher risk of developing seizures than risperidone.Conclusion: These findings suggest that antipsychotics should be used with caution in pediatric patients, especially regarding initial exposure, high dose, and polypharmacy.

Background: Tuberculosis (TB) has significant effects on patients’ health-related quality of life (HRQOL) and this study was conducted to evaluate the HRQOL based on EQ-5D utility score according to various health statuses of TB patients.Methods: A systematic literature review was conducted to select articles on HRQOLs outcomes of TB patients since 2000. A total of 1,710 articles were searched for primary screening and seven studies that directly assessed all types of TB patients using the EQ-5D were finally selected.Results: The EQ-5D scores of TB patients were in the ranges of 0.43–0.70. After the completion of TB treatment, the utility weights increased to the ranges of 0.88–0.98 and the EQ VAS values showed similar trend as the results of the EQ-5D. The EQ-5D score for multi-drug-resistant TB was very low at 0.51 during treatment but increased to 0.88 after the treatment was completed. The utility weights of latent TB were not significantly different from those of the general population.Conclusion: This study showed that the HRQOL based on the EQ-5D utility score of TB patients has significantly decreased, and the TB treatment has a significantly positive effect on the quality of life of patients.

Background: Adherence to tuberculosis (TB) drugs is one of the key aspects of global TB control, yet there is a lack of epidemiological evidence on the factors influencing adherence to TB drugs. Thus, this study aimed to explore the adherence and factors associated with adherence among TB patients in South Korea.Methods: We conducted a cohort study using a sampled national healthcare database from 2017 to 2018. Our study population included incident TB patients initiating quadruple or triple regimen who were available for follow-up for 180-days. Adherence was evaluated using the proportion of days covered (PDC): 1) adherent group: patients with PDC ≥80%; 2) non-adherent group: patients with PDC

Abstract Background A regular menstrual cycle is an important indicator of a healthy reproductive system. Previous studies reported obesity, stress, and smoking as the factors that are associated with irregular menstruation and early menopause. However, the integrative effects of these modifiable risk factors have not been fully understood. This study aimed to investigate the modifiable risk factors of menstrual cycle irregularity and premature menopause, as well as their individual and combined effects among adult women in Korea. Method This study selected adult women aged 19 years and above who had been included in the 2007–2014 Korean National Health and Nutrition Examination Survey. We used a separate dataset to analyze the risk factors of menstrual cycle irregularity and menopause (pre- and postmenopausal women: n = 4788 and n = 10,697, respectively). Univariate and multiple logistic regression analyses were conducted to evaluate the effects of smoking, drinking, obesity, and perceived level of stress on the menstrual cycle and menopause. Both logit and linear models were used in the analyses of the association between smoking and menopausal age. Equivalized household income, marital status, and educational level were considered as covariates. The modifiable risk factor scores were also calculated to integrate the effect of smoking, drinking, and obesity in the analysis. Result Results showed that smoking status, pack-year, obesity, and perceived level of stress were significantly associated with irregular menstruation among premenopausal women. Especially, women demonstrating > 3 modifiable risk factor scores had 1.7 times higher risk of having irregular menstruation than those who had a 0 score. Meanwhile, early initiation of smoking (≤19 years) and high pack-year (≥5) were also significantly associated with premature menopause among postmenopausal women. Conclusion This study demonstrated that modifiable risk factors, such as smoking, obesity, and stress, were significantly associated with menstrual cycle irregularity. Lifetime smoking was also correlated with early menopause. Our results suggested that healthier lifestyle practices, including, cessation of smoking, weight control, and stress management, were important factors in improving the reproductive health of women throughout life.

We evaluated the survival rates and medical expenditure in patients with lung cancer using a nationwide claims database in South Korea. A retrospective observational cohort study design was used, and 2,919 lung cancer patients and their matched controls were included. Medical expenditures were analyzed with the Kaplan-Meier sample average method, and patients were categorized into 4 groups by operation and primary treatment method (i.e. Patients with operation: OP = surgery, OP+CTx/RTx = surgery with anti-cancer drugs or radiotherapy; Patients without operation: CTx/RTx = anti-cancer drugs or radiotherapy, Supportive treatment). The 5-year medical expenditure per case was highest in the OP+CTx/RTx group ($36,013), followed by the CTx/RTx ($23,134), OP ($22,686), and supportive treatment group ($3,700). Lung cancer-related anti-cancer drug therapy was the major cost driver, with an average 53% share across all patients. Generalized linear regression revealed that monthly medical expenditure in lung cancer patients, after adjustment for follow-up month, was approximately 3.1-4.3 times higher than that in the control group (cost ratio for OP = 3.116, OP+CTx/RTx = 3.566, CTx/RTx = 4.340, supportive treatment = 4.157). The monthly medical expenditure at end of life was estimated at $2,139 for all decedents, and approximately a quarter of patients had received chemotherapy in the last 3 months. In conclusion, this study presented the quantified treatment costs of lung cancer on various aspects compared with matched controls according to the treatment of choice. In this study, patients with operation incurred lower lifetime treatment costs than patients with CTx/RTx or supportive treatment, indicating that the economic burden of lung cancer was affected by treatment method. Further studies including both cancer stage and treatment modality are needed to confirm these results and to provide more information on the economic burden according to disease severity.

BACKGROUND:Several studies have examined the risk and health outcomes related to polypharmacy among the elderly. However, information regarding polypharmacy among pediatric patients is lacking. OBJECTIVE:The aim of this study was to investigate the prevalence of polypharmacy and its related factors among the pediatric population of South Korea. METHODS:We used national claim data from the Health Insurance Review and Assessment Service-Pediatric Patients Sample (HIRA-PPS) in Korea originating from 2012 through 2016. Polypharmacy was defined as a daily average of two or more drugs used yearly. Complex chronic conditions (CCCs) were examined to evaluate concomitant chronic diseases in pediatric patients. Age-specific contraindications and potential drug-drug interactions were assessed according to criteria established by the Korea Institute of Drug Safety & Risk Management (KIDS). Descriptive statistics and logistic regression were conducted to analyze the status of polypharmacy and its associated risk factors in pediatric patients. RESULTS:The 5-year prevalence of pediatric polypharmacy in pediatric patients was 3.7%. The prevalence of polypharmacy was much higher in younger pediatric patients: 9.5% for patients between the ages of 1-7 years, 0.9% for ages 6-11 years, and 1.1% for ages 12-19 years. Pediatric patients with CCCs, Medical Aid benefits, or a hospital admission history had a significantly higher prevalence of polypharmacy when compared to their counterparts without those conditions. The most commonly prescribed drugs were respiratory agents (29%) followed by anti-allergic drugs (18.7%), central nervous system agents (15.9%), antibiotics (10.1%), and gastrointestinal drugs (7.7%). There was a positive correlation between the daily average number of inappropriate prescriptions and the degree of polypharmacy, especially in pediatric patients between the ages of 1-7 years. Contraindications and potential drug-drug interactions occurred in 11.0% and 10.1% of patients exposed to polypharmacy, respectively. CONCLUSIONS:One in ten pediatric patients under the age of 7 years was prescribed two or more concurrent drugs on average per day. Furthermore, pediatric patients exposed to polypharmacy showed an increased risk of inappropriate drug use. The implementation of a medication review system that considers pediatric patient polypharmacy exposure would reduce inappropriate drug use and prevent unwanted adverse outcomes.

Korea has the highest burden of tuberculosis (TB) among Organization for Economic Co-operation and Development countries. Various strategies have been implemented to eradicate TB in Korea, and it is critical to evaluate previous TB management outcomes before framing future TB policies. Over the past few decades, the rapid increase in the aging population in Korea has substantially impacted the incidence of TB among the elderly. Thus, in this study, we aimed to develop a mathematical model for the assessment of TB management outcomes incorporating special features of TB transmission dynamics in Korea. First, we incorporate 2-age groups in our TB model because TB epidemics in Korea are different between the elderly and the non-elderly (

Background/AimsEndoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC) that has demonstrated a minimal risk of lymph node metastasis in retrospective studies. We sought to prospectively evaluate the short-term outcomes of ESD treatment in EGCs.Methods : A prospective multicenter cohort study of neoplasms 3 cm or less in diameter at endoscopic size evaluation was performed in 12 Korean ESD study group-related university hospitals and the National Cancer Center. Resected specimens were evaluated by the central pathologic review board.Results : A patient cohort (n=712) with a total of 737 EGCs was analyzed. The margin-freeen bloc resection rate was 97.3%, and curative resection of 640 lesions (86.8%) was achieved. Lower curative resection rates were associated with lesions 2 to 3 cm in size prior to ESD compared with lesions 2 cm or less in size (78.6% vs 88.1%, respectively, p=0.009). Significant factors associated with noncurative resection were moderately or poorly differentiated histological type, posterior wall tumor location, tumor size larger than 3 cm, ulceration, and submucosal invasion. Delayed bleeding occurred in 49 patients (6.9%), and 12 patients (1.7%) exhibited perforations.Conclusion : sESD is an effective treatment with a high curative resection rate for EGCs that meets relatively conservative pre-ESD indications. Long-term survival outcomes should be evaluated in follow-up studies.

BACKGROUND:The National Liver Cancer Surveillance Program (NLCSP) targets patients with liver diseases that lead to liver cancer in South Korea. This study aimed to investigate the risk of liver disease leading to liver cancer using nationally representative data to establish an efficient NLCSP. METHODS:This study used data from the National Health Insurance Service National Sample Cohort (NHIS-NSC) from 2002 to 2013. A retrospective matched cohort design was applied to compare the development of liver cancer in patients with and without liver disease. Cox- proportional hazard regression for liver cancer with competing risk of death was performed for all subjects or each group stratified according to age or income level. RESULTS:A total of 66,192 patients with liver disease and matched subjects without liver disease were included in the study. The incidences of liver cancer among patients with and without liver disease within a median 8-year follow-up period were 2.68% (n = 1,772) and 0.34% (n = 210), respectively. Cox- regression analysis for liver cancer incidence indicated that cirrhosis had the highest risk (hazard ratio [HR]: 18.13, 95% confidence interval [CI]: 15.24-21.58), followed by hepatitis B (HR: 9.32, 95% CI: 8.00-10.85). Subgroup analysis showed that the presence of liver disease was an important risk factor in younger as well as elderly people, and a higher risk of liver disease was also observed in the patients with Medicaid. CONCLUSIONS:Attention should be paid to the development of liver cancer in young people under 50 years old and preventive efforts to decrease the incidence of liver cancer among Medicaid recipients is needed.

Few studies have assessed the long-term medical costs and incidence of obesity and overweight in Asia. We evaluated the impact of body mass index (BMI) on medical expenditures and disease incidence and prevalence over more than 10 years in South Korea.Using 2002-2013 data from the Korean National Claims Database, we analysed two population sets (initial BMI in 2002-2003; consistent BMI in 2002-2003 and 2012-2013). Obesity was defined by Asian BMI criteria. Incremental medical expenditures or Charlson Comorbidity Index (CCI) ratios for obese compared to normal weight individuals were calculated. Medical expenditure over 11 years was estimated by BMI using a generalised linear model. Individual obesity-related disease incidence was determined and adjusted hazard ratios were calculated.Data for 496,469 and 214,477 individuals were included in the entire and consistent BMI level populations, respectively. Average CCI score change in normal weight and the obesity III (BMI 35-59.99 kg/m2) group over 11 years were 0.94 and 1.56, respectively in the entire population, and incremental ratio in the obesity III group was 66.0% compared to the normal weight group. In consistent BMI level population, incremental ratio (92.1%) for obesity III was higher than entire population. Medical costs in the obesity III groups versus the normal weight group in the entire and consistent BMI level populations increased by 38.4% and 77.1%, respectively. Over 11 years, individuals with BMI ≥30 kg/m2 in the entire and consistent BMI level populations had post-adjustment medical expenditures of 1.13-1.20 and 1.21-1.40 times the normal weight group, respectively. Incidence rate and adjusted hazard ratio of obesity-related disease increased in the obesity groups compared to the normal weight group.Our findings emphasize the importance of the effective and sustainable obesity management strategies, considering the dramatic increase in obesity (BMI ≥30 kg/m2) in South Korea.

Background: Asian countries including Korea face aging populations and lack well-designed social welfare systems for the elderly. The objective of this study was to compare the out-of-pocket (OOP) medication expenditure burden of elderly and nonelderly patients with chronic conditions and to identify those vulnerable to expenditure burden. Methods: We analyzed data from the Korea Health Panel. We examined annual OOP medication expenditures in 2008, financial burden of OOP medication expenditures, and subjective feelings regarding the expenditure burden of elderly and nonelderly people. We conducted descriptive analyses and multiple regression analyses for those variables. Results: One in 10 elderly people taking drugs for chronic conditions spent more than 10% of their income on medication, and the probability of having an expenditure burden among elderly persons was 3.8 times as high as that among the nonelderly. The low-income status of elderly Koreans, combined with the coinsurance payment policy, may result in a large medication cost burden. Conclusion: Compared to nonelderly people in Korea, the elderly had greater OOP medication expenditures and were more vulnerable to OOP medication expenditure burden. In countries where social security systems are not sufficiently developed, payment policies for pharmaceuticals that consider the income status of the poor elderly need to be implemented.

Dementia is a major concern among growing chronic diseases in the aging society and its association with polypharmacy has not been adequately assessed. The objective of this study was to determine the association between polypharmacy and dementia through multiple statistical approaches. We conducted a nested case-control study for newly diagnosed dementia cases using the South Korean National Health Insurance Service sample cohort database (2002-2013, n = 1,025,340). Interactions between polypharmacy (an average use of ≥5 prescription drugs daily) and comorbidities or potentially inappropriate medications (PIMs) were tested. The odds ratios (ORs) for dementia were analyzed according to the presence of comorbidities, PIM uses, the average number of prescribed daily drugs, and significant interactions with polypharmacy using univariate and multiple logistic regression analyses. A higher prevalence of comorbidities, history of PIM use, higher PIM exposure, and higher proportion of polypharmacy were noted among cases than in controls. In the univariate analysis, the OR for dementia increased significantly with the increase in the number of prescribed drugs [1-

BACKGROUND:Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis. METHODS:We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases. RESULTS:A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied. CONCLUSIONS:This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.

Background: Gastrectomy for gastric cancer is associated with postoperative changes in cardiovascular risk factors, however, the impact of gastrectomy on cardiovascular events remains unclear. The authors assessed the incidence of cardiovascular events between patients undergoing gastrectomy or endoscopic resection for gastric cancer, and the general population. Materials and methods: This retrospective nationwide cohort study included patients with gastric cancer undergoing gastrectomy (n =37 698), endoscopic resection (n=2773), and matched control population (n= 161 887) between 2004 and 2013. The authors included patients without a history of cancer other than gastric cancer, myocardial infarction, or ischemic stroke. The primary outcome was the incidence of major adverse cardiovascular events (MACE) such as acute myocardial infarction, revascularization, or acute ischemic stroke, in patients with gastric cancer. Results: Among patients who underwent gastrectomy for gastric cancer, 2.9% (4.69 per 1000 person-years) developed novel MACE within the 1-year follow-up period. The gastrectomy group demonstrated a significantly decreased risk for MACE than the control population [hazard ratio (HR), 0.65; 95% CI: 0.61-0.69; P<0.001). Among the patients undergoing endoscopic resection for gastric cancer, 5.4% (8.21 per 1000 person-years) developed novel MACE within the 7-year follow-up period. The risk for MACE in the endoscopic resection group was not significantly different from the control population. Conclusion: Patients with gastric cancer who have undergone gastrectomy exhibit a reduced risk of cardiovascular diseases in comparison to the general population. In contrast, the risk for cardiovascular diseases in patients with gastric cancer who underwent endoscopic resection did not demonstrate a significant difference in cardiovascular risk in comparison to the general population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with gastric cancer (GC) experience 2 characteristic treatment modalities (gastrectomy or endoscopic resection), which may induce heterogeneity in the risk of post-cancer treatment type 2 diabetes (T2D). We investigated differences in the risk for T2D development in survivors of GC according to the 2 treatment methods. STUDY DESIGN: This retrospective nationwide population-based cohort study included 14,646 patients with GC who underwent gastrectomy (n = 12,918) or endoscopic resection (n = 1,728). We enrolled patients who survived for at least 5 years after gastrectomy or endoscopic resection, had no history of diabetes, and had not received adjuvant chemotherapy. T2D risk was evaluated using Cox regression for the gastrectomy group and compared to that of the endoscopic resection group. Because of the competing risks of incident T2D and death, a competing risk regression was performed. RESULTS: After a median follow-up duration of 8.1 years, the incidence rates of T2D in the endoscopic resection group and gastrectomy group were 7.58 and 6.98 per 1,000 person-years, respectively. Patients undergoing gastrectomy showed a significantly higher risk for developing T2D than patients undergoing endoscopic resection (hazard ratio [HR], 1.37; 95% CI 1.18 to 1.58; p < 0.0001). In subgroup analyses, gastrectomy was associated with increased T2D risk in female patients (HR, 1.72; 95% CI 1.22 to 2.43; p = 0.030 for interaction). CONCLUSIONS: Among GC survivors, patients undergoing gastrectomy showed a 37% increased risk of T2D development compared to patients undergoing endoscopic resection. Subgroup analyses showed that T2D risk increased by up to 72% in female patients. These results provide insights for establishing screening and preventive strategies for GC survivors to prevent T2D according to different treatment modalities. [ABSTRACT FROM AUTHOR]