Influenza and the risk of active tuberculosis occurrence among individuals with latent tuberculosis infection: A national cohort study in South Korea (2015-2020).

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.

Discontinuation of blood pressure-lowering, glucose-lowering, and lipid-lowering medications after bariatric surgery in patients with morbid obesity: a nationwide cohort study in South Korea.

BACKGROUND: Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients. OBJECTIVES: To investigate the patterns in the use of blood pressure-lowering, glucose-lowering, and lipid-lowering medications following BS in Korean patients with morbid obesity. SETTING: This study is a retrospective cohort study using the Health Insurance Review and Assignment claims database of South Korea (from 2019 to 2021). METHODS: We included patients who underwent BS between 2019 and 2020 in South Korea. We evaluated the treatment patterns of blood pressure-lowering, glucose-lowering, and lipid-lowering medications at 3-month intervals for 1-year following BS, including medication use, individual medication classes, and the number of medications prescribed. Furthermore, we estimated remission rates for each disorder based on patient characteristics by defining patients who discontinued their medications for at least 2 consecutive quarters as remission. RESULTS: A total of 3810 patients were included in this study. For 1-year following BS, a marked decrease in the number of patients using blood pressure-lowering, glucose-lowering, and lipid-lowering medications was observed. The most remarkable decrease occurred in glucose-lowering medications, which decreased by approximately -75.1% compared with that at baseline. This tendency was consistently observed when analyzing both the number of medications prescribed and the specific medication classes. Regarding remission rates, patients who were female, younger, and received the biliopancreatic diversion-duodenal switch as their BS showed a relatively higher incidence of remission than other groups. CONCLUSIONS: BS was associated with a decrease in the use of medications for hypertension, diabetes mellitus (DM), and dyslipidemia.

Comparison of active tuberculosis occurrence associated with Janus kinase inhibitors and biological DMARDs in rheumatoid arthritis.

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.

Long-term cardiovascular risk reduction after gastric cancer surgery: a nationwide cohort study.

BACKGROUND: Gastrectomy for gastric cancer is associated with postoperative changes in cardiovascular risk factors, however, the impact of gastrectomy on cardiovascular events remains unclear. We 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=2,773), and matched control population(n=161,887) between 2004 and 2013. We 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 seven-year follow-up period. The gastrectomy group demonstrated a significantly decreased risk for MACE than the control population (hazard ratio[HR], 0.65; 95% confidence interval[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 seven-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.

Incidence of tuberculosis disease in individuals diagnosed with tuberculosis infection after screening: A population-based cohort study in South Korea.

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 <80%) rates were 36% for 9 months of treatment with isoniazid, 22% for 4 months of treatment with rifampicin, and 18% for 3 months of treatment with isoniazid and rifampicin. Non-adherence to TPT did not lead to a decrease in the risk of TB incidence, whereas adherence to TPT (MPR ≥80%) reduced the risk of TB incidence by up to 72%. CONCLUSIONS: This study reveals increased adherence with shorter TPT regimens in a national TBI cohort, emphasizing the pivotal role of medication adherence in preventing TB.

Assessing the Labeling Information on Drugs Associated With Suicide Risk: Systematic Review.

BACKGROUND: Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on rare ADRs, such as suicide. OBJECTIVE: We aimed to systematically review case reports on DIS to provide evidence-based drug information. METHODS: We searched PubMed to obtain case reports regarding DIS published until July 2021. Cases resulting from drugs that are no longer used or are nonapproved, substance use, and suicidal intentions were excluded. The quality of each case report was assessed using the CASE (Case Reports) checklist. We extracted data regarding demographics, medication history, suicide symptoms, and symptom improvement and evaluated the causality of DIS using the Naranjo score. Furthermore, to identify the potential suicidal risk of the unknown drugs, we compared the results of the causality assessment with those of the approved drug labels. RESULTS: In 83 articles, we identified 152 cases involving 61 drugs. Antidepressants were reported as the most frequent causative drugs of DIS followed by immunostimulants. The causality assessment revealed 61 cases having possible, 89 cases having probable, and 2 cases having definite relationships with DIS. For approximately 85% of suspected drugs, the risk of suicidal ADRs was indicated on the approved label; however, the approved labels for 9 drugs, including lumacaftor/ivacaftor, doxycycline, clozapine, dextromethorphan, adalimumab, infliximab, piroxicam, paclitaxel, and formoterol, did not provide information about these risks. CONCLUSIONS: We found several case reports involving drugs without suicide risk information on the drug label. Our findings might provide valuable insights into drugs that may cause suicidal ADRs.

Cardiovascular risk of Janus kinase inhibitors compared with biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis without underlying cardiovascular diseases: a nationwide cohort study.

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.

Psychiatric Comorbidities and Schizophrenia in Youths With Attention-Deficit/Hyperactivity Disorder.

Importance: The association between attention-deficit/hyperactivity disorder (ADHD) and schizophrenia has received increased attention; however, evidence on the association between psychiatric comorbidities and subsequent schizophrenia in patients with ADHD is limited. Objective: To investigate the risk of being diagnosed with schizophrenia in children and adolescents with ADHD considering the presence of psychiatric comorbidity. Design, Setting, and Participants: This was a population-based, retrospective cohort study using the Health Insurance Review and Assessment claims database from January 1, 2007, to December 31, 2019. Participants were children and adolescents aged 5 to 19 years who received an ADHD diagnosis between January 1, 2010, and December 31, 2018, in the nationwide claims data of Korea. Data were analyzed from January 2010 to December 2019. Interventions or Exposures: The presence of psychiatric comorbidity was assessed from diagnosis records within 1 year before ADHD diagnosis. Comorbidities were further categorized according to the number of comorbidities and specific comorbid disorders. Main Outcomes and Measures: Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs, examining the association between psychiatric comorbidities and the risk of being diagnosed with schizophrenia. Furthermore, the occurrence of psychiatric comorbidity during the follow-up period was explored among patients without psychiatric comorbidity at baseline. Results: A total of 211 705 patients with newly diagnosed ADHD were included. A total of 157 272 patients (74.3%) were male, and the age of 5 to 9 years showed the highest distribution (115 081 patients [54.4%]). Patients with psychiatric comorbidity had a significantly higher risk of being diagnosed with schizophrenia than those without (adjusted HR, 2.14; 95% CI, 2.05-2.23). The association between schizophrenia and psychiatric comorbidity became progressively greater with the increasing number of comorbidities. Several individual psychiatric disorders showed an association with development of schizophrenia, with ASD, intellectual disability, tic disorder, depression, and bipolar disorder being the top 5 disorders most associated. Furthermore, 3244 patients (73.8%) without psychiatric comorbidities experienced the emergence of other psychiatric disorders before schizophrenia occurrence. Conclusions and Relevance: In this retrospective cohort study involving children and adolescents with ADHD, the presence of psychiatric comorbidity in patients with ADHD was associated with an increased risk of being diagnosed with schizophrenia, with an increased risk observed in multiple comorbidities and a wide variety of comorbidities. These findings highlight the significance of assessing and managing psychiatric comorbidities in patients with ADHD to decrease subsequent schizophrenia risk and allow for early intervention.

Performance of Cardiovascular Risk Prediction Models in Korean Patients With New-Onset Rheumatoid Arthritis: National Cohort Study.

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.

Comparative Risk of Type 2 Diabetes after Gastrectomy and Endoscopic Resection for Gastric Cancer: A Nationwide Cohort Study.

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.

The relative importance of friendship to happiness increases with age.

Happiness is predicted by social relationships in general and contact frequency in particular. This study aims to examine if the relative importance of social contacts with the closest family/relative, friend, and neighbor in happiness changes with advancing age. We used data for all participants aged 19 years and older (n = 229,099) in the 2019 Community Health Survey, which measured the frequency of contact with the closest relative/family, neighbor, and friend among a representative sample of Koreans between August 16 and October 31, 2019. The Shapley value decomposition method was used to measure the relative importance of each predictor of happiness. Overall, contact frequency was positively associated with happiness (p<0.001). The relative importance value of contact with the closest family, neighbor, and friend to happiness increased from 4.70%, 3.98%, and 7.35%, respectively, in the 19-29 years group to 8.09%, 4.44%, and 11.00%, respectively, in the 60 years and older group. Frequent interactions with the closest friend could have a greater impact on happiness in old age than those with the closest family and neighbor.

Cost-Effectiveness of All-Oral Regimens for the Treatment of Multidrug-Resistant Tuberculosis in Korea: Comparison With Conventional Injectable-Containing Regimens.

BACKGROUND: Regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) have been changed from injectable-containing regimens to all-oral regimens. The economic effectiveness of new all-oral regimens compared with conventional injectable-containing regimens was scarcely evaluated. This study was conducted to compare the cost-effectiveness between all-oral longer-course regimens (the oral regimen group) and conventional injectable-containing regimens (the control group) to treat newly diagnosed MDR-TB patients. METHODS: A health economic analysis over lifetime horizon (20 years) from the perspective of the healthcare system in Korea was conducted. We developed a combined simulation model of a decision tree model (initial two years) and two Markov models (remaining 18 years, six-month cycle length) to calculate the incremental cost-effectiveness ratio (ICER) between the two groups. The transition probabilities and cost in each cycle were assumed based on the published data and the analysis of health big data that combined country-level claims data and TB registry in 2013-2018. RESULTS: The oral regimen group was assumed to spend 20,778 USD more and lived 1.093 years or 1.056 quality-adjusted life year (QALY) longer than the control group. The ICER of the base case was calculated to be 19,007 USD/life year gained and 19,674 USD/QALY. The results of sensitivity analyses showed that base case results were very robust and stable, and the oral regimen was cost-effective with a 100% probability for a willingness to pay more than 21,250 USD/QALY. CONCLUSION: This study confirmed that the new all-oral longer regimens for the treatment of MDR-TB were cost-effective in replacing conventional injectable-containing regimens.

Prevalence and causative drugs of drug-induced Parkinsonism in pediatric patients.

Although several studies provided evidence on the epidemiology of drug-induced Parkinsonism (DIP) and its causative drugs, it is still limited in pediatrics. This study aimed to investigate the prevalence and risk of DIP in pediatrics. We used the Health Insurance Review and Assessment Service-Pediatric Patients Sample in Korea between 2010 and 2017 to estimate the annual prevalence of DIP and causative drug use using a cross-sectional design. The risk of DIP associated with causative drugs was evaluated using a case-crossover design. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated using a conditional logistic regression. A total of 2925 pediatric patients had diagnosed with DIP from 2010 to 2017. Most patients were aged between 12 and19 years old, and 99.8% had any diagnosis of mental health disorder (MHD). During the study period, the prevalence of DIP increased by 10.0-fold from 2010 to 2017. All causative drugs showed a corresponding increase in their use, with atypical antipsychotics being the most prominent (increase ratio, 2.07). For both in the prevalence of DIP and atypical antipsychotic use, the increment was much bigger in patients with non-psychotic MHD than that in patients with psychotic MHD. In the case-crossover study, antipsychotics showed the largest aOR with DIP. Risperidone among antipsychotics showed the highest risk for DIP (aOR = 7.09, 95% CI = 3.83-13.09), followed by aripiprazole (aOR = 5.03, 95% CI = 2.88-8.80). This study suggests that the increase in DIP prevalence in pediatric patients might be because of the increased use of atypical antipsychotics.

The association between weight change after gastric cancer surgery and type 2 diabetes risk: A nationwide cohort study.

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 < -10% of postoperative weight decrease (hazard ratio, 0.65; 95% confidence interval, 0.49-0.87; P = 0.004) had the lowest type 2 diabetes risk. A non-linear association occurred between postoperative weight decrease and the type 2 diabetes risk in gastrectomy recipients (Akaike's information criterion [AIC] for non-linear model, 5423.52; AIC for linear model, 5425.61). CONCLUSIONS: A U-shaped non-linear association occurred between the type 2 diabetes risk and postoperative weight decrease in gastric cancer survivors who underwent gastrectomy. The lowest type 2 diabetes risk occurred in patients with ≥ -15% to < -10% of postoperative weight decrease at 3 years.

Supervised Relation Extraction Between Suicide-Related Entities and Drugs: Development and Usability Study of an Annotated PubMed Corpus.

BACKGROUND: Drug-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. OBJECTIVE: This 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. METHODS: We 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. RESULTS: Our 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. CONCLUSIONS: To our knowledge, this is the first and most extensive corpus of drug-suicide relations.

Association of Uncontrolled Hypertension or Diabetes Mellitus With Major Adverse Cardiovascular Events and Mortality in South Korea: Population-Based Cohort Study.

BACKGROUND: Managing 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. OBJECTIVE: We aimed to examine the association of uncontrolled HT or DM with the incidence of cardiovascular events or deaths from any cause. METHODS: This 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. RESULTS: Among 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. CONCLUSIONS: This 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.

Incidence and risk factors of tuberculosis in patients following gastrectomy or endoscopic submucosal dissection: a cohort analysis of country-level data.

BACKGROUND: Gastric cancer adversely affects nutrition and immunity, while increasing the risk of tuberculosis (TB). This study investigated the incidence and risk factors for TB in gastric cancer patients who had undergone gastrectomy or endoscopic submucosal dissection (ESD). METHODS: This retrospective cohort study was conducted using Korean national insurance claims data. We defined three study groups (total gastrectomy, subtotal gastrectomy, and ESD) of patients diagnosed with gastric cancer plus a cancer-free control group. The latent TB infection (LTBI) screening status, TB incidence, and potential confounders in each cohort were analyzed, and the risk of TB was analyzed using a Cox proportional hazard model. RESULTS: LTBI tests were performed in less than 1% of all patients, and the TB incidence rates were 473.8, 287.4, 199.4, 111.1 events/100,000 person-years in the total gastrectomy, subtotal gastrectomy, ESD, and control cohorts, respectively. Compared to the control cohort, the total gastrectomy cohort showed the highest hazard ratio (HR) for TB incidence (HR: 2.896, 95% CI: 2.559-2.337), while the ESD cohort showed a significantly increased risk (HR: 1.578, 95% CI: 1.957-1.980). Age, body mass index, and lack of exercise were risk factors in all cohorts. Comorbidities were also considered risk factors, depending on the cohort type. CONCLUSIONS: Patients who underwent gastrectomy or ESD had an increased risk of TB, and this risk was correlated with the scope of gastrectomy. Considering the low rate of LTBI diagnostic tests and increased risk of TB in the study cohorts, more specific and practical guidelines for TB management are required for gastric cancer patients.

Real-world association of adherence with outcomes and economic burden in patients with tuberculosis from South Korea claims data.

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.

Comparison of prediction methods for treatment continuation of antipsychotics in children and adolescents with schizophrenia.

OBJECTIVE: There is little evidence for finding optimal antipsychotic treatment for schizophrenia, especially in paediatrics. To evaluate the performance and clinical benefit of several prediction methods for 1-year treatment continuation of antipsychotics. DESIGN AND SETTINGS: Population-based prognostic study conducting using the nationwide claims database in Korea. PARTICIPANTS: 5109 patients aged 2-18 years who initiated antipsychotic treatment with risperidone/aripiprazole for schizophrenia between 2010 and 2017 were identified. MAIN OUTCOME MEASURES: We used the conventional logistic regression (LR) and common six machine-learning methods (least absolute shrinkage and selection operator, ridge, elstic net, randomforest, gradient boosting machine, and superlearner) to derive predictive models for treatment continuation of antipsychotics. The performance of models was assessed using the Brier score (BS), area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). The clinical benefit of applying these models was also evaluated by comparing the treatment continuation rate between patients who received the recommended medication by models and patients who did not. RESULTS: The gradient boosting machine showed the best performance in predicting treatment continuation for risperidone (BS, 0.121; AUROC, 0.686; AUPRC, 0.269). Among aripiprazole models, GBM for BS (0.114), SuperLearner for AUROC (0.688) and random forest for AUPRC (0.317) showed the best performance. Although LR showed lower performance than machine learnings, the difference was negligible. Patients who received recommended medication by these models showed a 1.2-1.5 times higher treatment continuation rate than those who did not. CONCLUSIONS: All prediction models showed similar performance in predicting the treatment continuation of antipsychotics. Application of prediction models might be helpful for evidence-based decision-making in antipsychotic treatment.

Association of Treatment With Antipsychotics, Antidepressants, or Both With Movement Disorders and Seizures Among Children and Adolescents With Depression in Korea.

Importance: Little evidence exists on neurological adverse events (movement disorders and seizures) that occur during adjuvant use of antipsychotics with antidepressants, especially in children and adolescents. Objective: To assess the association between neurological adverse events (movement disorders, including parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tic, and seizures) and the adjuvant use of antipsychotics in children and adolescents with depression. Design, Setting, and Participants: A retrospective cohort study using the Health Insurance Review and Assessment claims database in Korea between 2008 and 2018. The study population was children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between January 1, 2010, and December 31, 2018. Data were analyzed between December 9, 2020, and December 10, 2021. Exposure: Time-varying exposure to antidepressants, antipsychotics, and concomitant use of antidepressants and antipsychotics. Concomitant use was further subdivided according to the antipsychotic treatment status (dose and agent). Main Outcomes and Measures: The extended Cox proportional hazards regression model, with adjustment for sex, age, health insurance type, psychiatric comorbidities, psychiatric hospitalization, and comedication with other psychotropic drugs, was used to estimate adjusted hazard ratios (aHRs) and 95% CIs for the associations of movement disorders and seizures with use of antidepressants and antipsychotics. Results: A total of 9890 patients were included in the study: 9541 (mean [SD] age, 14.8 [2.8] years; 4956 [51.9%] female) and 7731 (mean [SD] age, 14.9 [2.7] years; 4150 [53.7%] female) met the inclusion criteria for movement disorders and seizures, respectively. For movement disorders, associations were found between concomitant use (aHR, 3.68; 95% CI, 3.06-4.44) and antipsychotic-only use (aHR, 3.84; 95% CI, 3.03-4.87) compared with antidepressant-only use, but their CIs overlapped. The associations with seizure were similar (concomitant use: aHR, 2.06; 95% CI, 1.66-2.55; antipsychotic-only use: aHR, 2.05; 95% CI, 1.53-2.75). With concomitant use, the aHRs gradually increased with increasing doses of antipsychotics. Haloperidol had the highest aHR, 7.15 (95% CI, 3.89-10.00) for movement disorders. The highest aHR for seizure was observed with quetiapine (aHR, 2.36; 95% CI, 1.55-3.59), followed by aripiprazole (aHR, 2.05; 95% CI, 1.52-2.77). Conclusions and Relevance: In this cohort study, adjunctive antipsychotics with antidepressants were associated with movement disorders and seizures compared with antidepressant monotherapy in children and adolescents with depression. These results suggest that careful consideration of the risk-benefit profile of the antipsychotic use as adjuvant therapy in this population is needed.