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.

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.

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.

Remission of type 2 diabetes after gastrectomy for gastric cancer: diabetes prediction score.

BACKGROUND: Although type 2 diabetes (T2D) remission after gastric cancer surgery has been reported, little is known about the predictors of postoperative T2D remission. METHODS: This study used data from a nationwide cohort provided by the National Health Insurance Service in Korea. We developed a diabetes prediction (DP) score, which predicted postoperative T2D remissions using a logistic regression model based on preoperative variables. We applied machine-learning algorithms [random forest, XGboost, and least absolute shrinkage and selection operator (LASSO) regression] and compared their predictive performances with those of the DP score. RESULTS: The DP score comprised five parameters: baseline body mass index (< 25 or ≥ 25 kg/m2), surgical procedures (subtotal or total gastrectomy), age (< 65 or ≥ 65 years), fasting plasma glucose levels (≤ 130 or > 130 mg/dL), and antidiabetic medications (combination therapy including sulfonylureas, combination therapy not including sulfonylureas, single sulfonylurea, or single non-sulfonylurea]). The DP score showed a clinically useful predictive performance for T2D remission at 3 years after surgery [training cohort: area under the receiver operating characteristics (AUROC) 0.73, 95% confidence interval (CI), 0.71-0.75; validation cohort: AUROC 0.72, 95% CI 0.69-0.75], which was comparable to that of the machine-learning models (random forest: AUROC 0.71, 95% CI 0.68-0.74; XGboost: AUROC 0.70, 95% CI 0.67-0.73; LASSO regression: AUROC 0.75, 95% CI 0.73-0.78 in the validation cohort). It also predicted the T2D remission at 6 and 9 years after surgery. CONCLUSIONS: The DP score is a useful scoring system for predicting T2D remission after gastric cancer surgery.

Risk of seizures associated with antipsychotic treatment in pediatrics with psychiatric disorders: a nested case-control study in Korea.

Antipsychotic drugs raise seizure risk in adults, and antipsychotic drug use is increasing among pediatric psychiatric disorder patients. However, few studies have examined seizure risk in this younger patient population. To evaluate seizure risk in pediatric patients on antipsychotics, we conducted a nested case-control study using a nationwide database. Patient information was retrieved from the Korean Health Insurance Review and Assessment (HIRA) database from 2008-2018. Antipsychotic use among newly diagnosed psychiatric patients was gathered starting 1 year before the index date and categorized as recent, past, consistent, or none. Seizure cases among these patients were defined based on (1) prescription of antiepileptic drugs or (2) an electroencephalography (EEG) examination among patients with seizure diagnostic code. A conditional logistic regression model was constructed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for seizure risk due to antipsychotic use. In total, 1523 seizure cases and 6092 seizure-free controls aged 8-19 years with newly diagnosed psychiatric disorders were included for analysis. Logistic regression revealed a significant association between antipsychotic use and seizure development (recent users OR = 4.03, 95% CI 3.4-4.79; consistent users: OR = 2.84, 95% CI 2.44-3.3). Seizure risk enhanced further with an increase in the number of antipsychotic drugs used. Risperidone, aripiprazole, quetiapine, olanzapine, paliperidone, and blonanserin were independently associated with greater seizure risk. Pediatric patients receiving antipsychotics, especially new or multiple antipsychotic users, should be carefully monitored for seizure development.

Lifetime survival and medical costs of lung cancer: a semi-parametric estimation from South Korea.

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.

The association between proton pump inhibitor use and the risk of tuberculosis: A case-control study.

PURPOSE: Few studies have reported an association between proton pump inhibitor (PPI) use and tuberculosis. Tuberculosis incidence is relatively high in Asian people, and an increase in PPI prescriptions has been reported in South Korea. Thus, we investigated the association between PPI use and tuberculosis development. METHODS: We conducted a case-control study on 25 672 newly diagnosed tuberculosis patients using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database (2002-2013). We selected a control group without tuberculosis using 1:1 exact matching based on age, sex, index year, insurance type, and income level. We investigated PPI exposure 2 years prior to the index date and classified the subjects into nonuser, continuous user, recent user, and former user groups. Odds ratios (ORs) and 95% confidence intervals (CIs) for tuberculosis development were calculated using conditional logistic regression. RESULTS: A total of 51 344 cases and controls were analyzed. Recent PPI use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.18-1.39) and continuous PPI use (aOR, 1.13; 95% CI 1.10-1.28) were significantly associated with tuberculosis development, compared with nonuse of PPIs. An increased tuberculosis incidence was not observed in the former use group compared with the nonuse group (aOR 1.05, 95% CI 0.95-1.17). CONCLUSIONS: In this case-control study, we found that recent PPI use and continuous PPI use were associated with increased tuberculosis development. Although further investigation is needed, the tuberculosis risk accompanying PPI treatment should be considered.

Positive Association Between Helicobacter pylori Infection and Metabolic Syndrome in a Korean Population: A Multicenter Nationwide Study.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection causes extra-gastrointestinal as well as gastric diseases. This analytical cross-sectional study was performed to investigate the association between H. pylori infection and metabolic syndrome in a Korean population. METHODS: Anthropometric and metabolic data, as well as anti-H. pylori IgG antibodies, were measured in 21,106 subjects who participated in a health checkup between January 2016 and June 2017. The classification of metabolic syndrome followed the revised National Cholesterol Education Program criteria. RESULTS: After excluding subjects with a history of H. pylori eradication therapy, or gastric symptoms, the seropositivity of H. pylori was 43.2% in 15,195 subjects. H. pylori-positive participants had significantly higher body mass index (BMI), waist circumference, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein (HDL-C) than did seronegative participants (P < 0.05). After adjusting for confounders, high TC, low HDL-C, and high LDL-C were associated with H. pylori seropositivity. Finally, the prevalence of metabolic syndrome was higher in H. pylori-seropositive subjects than in negative ones (27.2% vs. 21.0%, P < 0.05), and H. pylori seropositivity increased the likelihood of metabolic syndrome (OR 1.19, 95% CI 1.09-1.31, P < 0.001) after adjusting for sex, age, BMI, smoking, residence, household income, and education level. However, the association between H. pylori seropositivity and metabolic syndrome disappeared in those ≥ 65 years old. CONCLUSIONS: H. pylori infection plays an independent role in the pathogenesis of metabolic syndrome in Koreans under 65 years old.

Drug holiday patterns and bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: There is limited evidence regarding the appropriate length of a bisphosphonate (BP) holiday to reduce the risk of osteonecrosis of the jaw (ONJ). In this cross-sectional study, we investigated the population-based patterns of the gaps between BP discontinuation and ONJ diagnosis. SUBJECTS AND METHODS: We used the claims database of the National Health Insurance Service in Korea. Among BP users between 2006 and 2015, incident ONJ cases during 2010-2015 with no history of ONJ in the last 4 years were identified. We assessed the time gap from the last BP administration to ONJ diagnosis. RESULTS: Among 1,569 incident ONJ cases, 836 (53.3%) occurred after BP discontinuation. The cumulative proportions of ONJ occurrence within 1 month, 3 months, 1 year, 2 years, and 3 years after discontinuation were 58.9%, 70.8%, 87.0%, 93.2%, and 96.1%, respectively. The length of drug holidays showed no significant difference between patients with or without comorbid cancer and diabetes mellitus (p-value, 0.12 and 0.52, respectively). However, the use of injectable BP formulations significantly affected ONJ incidence (p < 0.01). CONCLUSIONS: Most ONJ cases occurred within 3 years from BP suspension, with a higher prevalence among BP injection users with 1 year or lesser BP holiday.

Sex differences in the association between asthma incidence and modifiable risk factors in Korean middle-aged and older adults: NHIS-HEALS 10-year cohort.

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.

Quality of life of middle-aged adults in single households in South Korea.

PURPOSE: The number of single households has increased worldwide with middle-aged people in such households indicating the highest increase. However, there is a lack of studies on the topic. This study estimated the quality of life (QOL) by household type for middle-aged Korean adults. METHODS: We used the Korea National Health and Nutrition Examination Survey data from 2007 to 2015. QOL was analyzed using EQ-5D 3-level, and demographic and health-related variables were included as confounders. The households were divided into single household, married couple without child, other one-generation, married couple with child, single parent with child, other two-generation, and three-generation. Logistic regression using level, strata, and sample weight of data was performed based on average QOL. RESULTS: This study included 18,147 responders aged 45-64 years, with single households constituting 5.7%. Single households having average or less QOL were 48.4%, with men and women constituting 40.1 and 53.3%, respectively. After adjusting socioeconomic factors and health-related factors, the odds ratio (OR) of single households was 1.375 (95% CI 1.122-1.684) compared to the three-generation group. According to the sex, the OR of single households with men was higher (OR 1.552, 95% CI 1.121-2.149). However, no significance was found in women. CONCLUSIONS: The study results revealed that middle-aged people in single households had low QOL than those in multi-person households. The trend was significantly observable in men than in women. Because middle-aged adults might transform into elderly with low QOL, program development and social support for middle-aged adults in single households should be provided.

Factors associated with menstrual cycle irregularity and menopause.

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.

Assessing the risk of type 2 diabetes mellitus among children and adolescents with psychiatric disorders treated with atypical antipsychotics: a population-based nested case-control study.

To examine the associations between atypical antipsychotic (AAP) exposure and the development of type 2 diabetes mellitus (T2DM) in Korean pediatric patients with psychiatric disorders, we conducted a nested case-control study using the claims data of the National Health Insurance system of Korea between 2010 and 2014. A cohort of patients with psychiatric disorders was identified, and enrollment was taken as the date of the first psychiatric diagnosis. Cases involved patients with a diagnosis of T2DM or prescriptions for glucose lowering drugs after enrollment, and the identification of T2DM was defined as the index date. We performed a conditional logistic regression analysis for matched case-control data to assess associations between AAP exposure and T2DM, and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) are presented. From 1,092,019 patients aged 2-19 years, we identified 20,263 cases with T2DM and 80,043 controls, matched by sex, age, enrollment date, and primary psychiatric diagnosis. After adjusting for comorbidities, psychotropic medication history, and the healthcare institution characteristics, the aOR of having T2DM was significantly higher in multi-AAP users compared with non-users (aOR 1.89; 95% CI 1.63-2.20). Particularly high ORs for T2DM were observed in clozapine users compared with non-users (aOR 3.47; 95% CI 1.88-6.41). We observed a linear relationship between the increase in risperidone dose and the increase in the risk of developing T2DM. Our findings suggest a significantly increased risk of developing T2DM in child or adolescent patients with psychiatric disorders exposed to AAPs compared with those not exposed to AAPs.

Effect of Helicobacter pylori Eradication and ABO Genotype on Gastric Cancer Development.

BACKGROUND: Evidence is lacking regarding how Helicobacter pylori infection status, eradication history, and ABO blood type affect the development of gastric cancer (GC) given the multifactorial and distinctive etiology according to cancer location (noncardia vs cardia) and histologic type (intestinal vs diffuse-type). We evaluated the effect of H. pylori infection status incorporated with H. pylori eradication history and ABO genotype on GC development according to cancer location and histologic type. METHODS: A case-control study of 997 patients with noncardia GC (NCGC) and 1147 control subjects was performed using risk analyses with 14 factors including H. pylori infection with eradication history and ABO genotype. As final analyses, multivariable logistic regression models were fitted. Additionally, H. pylori infection status with eradication history was tested for its association with age, atrophic gastritis (AG), and intestinal metaplasia (IM). RESULTS: The ABO genotype with the B allele was associated with a significantly lower risk of NCGC of both histologic types. The reduction in risk for NCGC by adding the B allele was more prominent in diffuse-type than that in the intestinal-type. H. pylori infection with eradication history was associated with a significantly lower risk of NCGC of both histologic types, compared with those without eradication history (odds ratio (OR), 0.22; 95% confidence interval (CI), 0.14-0.34) approaching that of uninfected subjects. Past infection status without an eradication history was associated with older age, AG, and IM. CONCLUSIONS: H. pylori eradication and the B allele decreased the risks of the intestinal and diffuse-types of NCGC. H. pylori eradication revealed a strong association against developing NCGC. Therefore, it should be considered as a primary measure in NCGC prevention.

Prescribed drugs and polypharmacy in healthcare service users in South Korea: an analysis based on National Health Insurance Claims data.

OBJECTIVE: This study was conducted to analyze and compare the exposure to individually prescribed drugs and the prevalence of polypharmacy according to age group and concomitant disease in South Korea. METHODS: The use of prescribed drugs was evaluated according to average numbers of prescription drugs used daily during a year or month, using the Korean Health Insurance Claims Database, which is representative of over 90% of citizens, in 2010 and 2011. The use of prescribed drugs was also analyzed according to concomitant diseases and age. Polypharmacy was defined as the use of 5 or more drugs daily during a specific observation period, and proportions of polypharmacy users were calculated according to comorbidity and age group. RESULTS: The annual average numbers of daily used prescription drugs in 2010 and 2011 were 0.3 (SD = 0.5), 0.4 (SD = 0.7), 1.2 (SD = 1.5), and 2.3 (SD = 2.0) for people aged < 20 years, 20-49 years, 50-64 years, and ≥ 65 years, respectively. Proportions of individuals demonstrating polypharmacy increased with age and were 9.5% and 44.1% for elderly individuals in the year- and month-based analyses, respectively. The annual average number of daily medications used increased by ~2 drugs in the concomitant disease group, and the higher mortality group used a higher number of prescribed drugs than the lower mortality group. CONCLUSIONS: The results highlight the elevated burden of multi-medication in elderly patients, and the study found that prescribed drug use increased with age and the number of concomitant diseases.

Evidence supporting the need for considering the effects of smoking on drug disposition and effectiveness in medication practices: a systematic narrative review.

This study was conducted to provide a narrative overview of interactions between smoking and drug effectiveness/ pharmacokinetics. Database searches were performed to identify review articles published prior to March 10, 2013. Eligible articles reporting altered pharmacokinetic profiles, drug response, or adverse drug effects due to drug-smoking interactions were selected. Information on mechanism of action and clinical effects from the selected articles (n = 83) were summarized by therapeutic drug class. For cardiovascular drugs, smoking effects were variable. Smoking reduced aspirin response but increased clopidogrel response by increasing active metabolites. Warfarin, which has a narrow therapeutic range, required dosage adjustment in smokers due to its rapid clearance. Smoking is a risk factor for respiratory disease, leading to a lower response to corticosteroid and requiring increased doses or additional drugs. Higher doses of theophylline and some antipsychotics, which are mainly metabolized by CYP1A2, are required to reach an optimal plasma concentration in smokers. Smoking is also a risk factor for cancer, especially for lung cancer. Erlotinib or gefitinib are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer and showed lower anticancer effects in smokers. This summary of the interactions between smoking and drug pharmacological properties will aid healthcare professionals in providing patients with appropriate drug therapies, and emphasizes the need for considering smoking status as a patient factor in the clinical setting.

Association of fracture risk with benzodiazepine among adults in South Korea.

This study examined the association between fracture and benzodiazepine (BZD) prescription in Korean adults using case-crossover (CCO) and self-controlled case-series (SCCS) designs, which have the advantage to control confounding bias, such as individual characteristics. Patients with fracture were defined as patients who visited the emergency room and orthopedics department with the ICD-10 diagnosis code for fracture. Fractures due to motor vehicle accidents and stroke were excluded. Whereas the CCO design presented odds ratio (OR) using a conditional logistic regression model, SCCS design showed incidence rate ratio (IRR) using a conditional Poisson regression model. The concomitant drugs that can affect the fracture were adjusted. Sensitivity analysis and subgroup analysis by age (elderly vs. nonelderly), action mechanism (short-acting vs. long-acting), and prescription duration (short-term user vs. long-term user) were conducted. The adjusted OR (AOR) for control period I (prior to 90 days from case) was 1.39 (95% CI=1.25-1.54) for all BZD prescriptions. The adjusted ORs for other control periods showed similar trends. The adjusted IRRs (AIRR) during the first 4 weeks, 4-8 weeks, 8-12 weeks, and 12-16 weeks from new BZD use were 1.46 (95% CI=1.28-1.66), 1.23 (95% CI=1.01-1.49), 1.09 (95% CI=0.86-1.37), and 1.38 (95% CI=1.07-1.77), respectively. Regardless of age group, action mechanism, or prescription duration, fracture risk was higher during case period than control. The risk for fracture was higher in both elderly and non-elderly people with BZD prescription than in those without BZD prescription. Careful monitoring for people who start BZD treatment and further research in the non-elderly is required.

New Glabretal Triterpenes from the Immature Fruits of Poncirus trifoliata and Their Selective Cytotoxicity.

Two new glabretal triterpenes, pancastatins A (1) and B (2), were isolated from the immature fruits of Poncirus trifoliata. Their chemical structures were elucidated by spectroscopic analyses including one- and two-dimensional NMR and high-resolution electrospray ionization mass spectrometry. Compounds 1 and 2 exhibited selective cytotoxicity against PANC-1 pancreatic cancer cells under low-glucose stress conditions.

In-depth investigation for prescribing trends of benzodiazepines in South Korea.

This study aimed to investigate national prescription trends of benzodiazepines (BZD) for adults between 2007 and 2011 using Health Insurance Review and Assessment Service (HIRA) database in South Korea. Data analysis was performed by claim unit or patient unit. For the analysis of patient unit, each claim was merged by the same patient. Defined daily dose (DDD) was used to analyze the data in terms of dose and periods of BZD prescription. We identified a total of 22,361,449 adult patients who had BZD prescription at least once in 1,989,263 claims during 5 years. The average national BZD prescription prevalence for 1 year was 23.7%, 7.9%, 4.7%, and 3.2% of >= 1 day supply, >= 30 days supply, >= 90 days supply, and >= 180 days supply, respectively. The trends for 5 years were very similar. Among study population, 87.7% visited only non-psychiatric departments and the most frequent indication was gastrointestinal related diseases. BZD consumption expressed as DDDs per 1,000 inhabitants per day was 109.2. BZD consumption tended to be ~ 4 x higher in elderly than that of non-elderly (268.6 vs. 60.0 in male and 367.7 vs. 90.9 in female). Our study indicated the possibilities for inappropriate prescription of BZD, and the limitation policy on continuous prescription over 30 days supply did not seem to be effective. The effective interventions including an educational program for appropriate prescription of BZD should be considered.