Eun Jin Jang

Use of inhaled corticosteroids and the risk of tuberculosis

Background Inhaled corticosteroid (ICS) use could decrease local immunity of the lung. Concerns have been raised regarding the risk of tuberculosis (TB) development among ICS users. The aim of this study was to elucidate the association between ICS use and development of TB among patients with various respiratory diseases in South Korea, an intermediate-TB-burden country. Methods A nested case-control study based on the Korean national claims database was performed. The eligible cohort consisted of 853 439 new adult users of inhaled respiratory medications between 1 January 2007 and 31 December 2010. Patients diagnosed as having TB after initiation of inhaled medication were included as cases. For each case individual, up to five control individuals matched for age, sex, diagnosis of asthma or chronic obstructive pulmonary disease (COPD) and initiation date of inhaler use were selected. Results From the cohort population, we matched 4139 individuals diagnosed as having TB with 20 583 controls. ICS use was associated with increased rate of TB diagnosis (adjusted OR (aOR), 1.20; 95% CI 1.08 to 1.34). The association was dose dependent (p for trend <0.001). A subgroup analysis revealed that ICS use increased the risk of TB development among non-users of oral corticosteroid (OCS) but not among OCS users. Conclusions ICS use increases the risk of TB in an intermediate-TB-burden country. Clinicians should be aware of the possibility of TB development among patients who are long-term high-dose ICS users.

Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance Database Study

Aims/Introduction This study aimed to estimate the prevalence of gestational diabetes mellitus (GDM) and use of anti-diabetic medications for patients with GDM in Korea, using data of the period 2007–2011 from the Health Insurance Review and Assessment (HIRA) database, which includes the claims data of 97% of the Korean population. Materials and Methods We used the Healthcare Common Procedure Coding System codes provided by the HIRA to identify women with delivery in the HIRA database between 2009 and 2011. GDM was defined according to ICD-10 codes, and patients with pre-existing diabetes between January 1, 2007 and pregnancy were excluded. A Poisson regression was performed to evaluate the trends in annual prevalence rates. Results The annual numbers of deliveries in 2009–2011 were 479,160 in 2009, 449,747 in 2010, and 377,374 in 2011. The prevalence of GDM during that period was 7.5% in 2009–2011: 5.7% in 2009, 7.8% in 2010, and 9.5% in 2011. The age-stratified analysis showed that the prevalence of GDM was highest in women aged 40–44 years, at 10.6% in 2009–2011, and that the annual prevalence significantly increased even in young women aged 20–29 years during that period (P < 0.05). More than 95% of the patients with GDM did not take any anti-diabetic medication. Among the anti-diabetic medications prescribed for patients with GDM, insulin was most commonly prescribed (for >98% of the patients with GDM on medication). Conclusions The prevalence of GDM in Korean women recently reached 5.7–9.5% in recent years. This represents a public health concern that warrants proper screening and medical care for GDM in women during the childbearing years.

Inhaled bronchodilators and the risk of tachyarrhythmias

BACKGROUND/OBJECTIVES There have been controversies about whether inhaled bronchodilators could increase the risk of clinically important tachyarrhythmias. We investigated the association between inhaled bronchodilators and the development of tachyarrhythmias, including atrial fibrillation and other paroxysmal tachyarrhythmias in real practice. METHODS We conducted a nested case-control study with the use of the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea). Overall, 3312 cases with newly developed tachyarrhythmias including atrial fibrillation and other paroxysmal tachyarrhythmias and 9732 matched (up to 1:5) controls were identified from 545,508 subjects without acute major cardiovascular events in the past year between January 1, 2011 and December 31, 2011. Conditional logistic regression analysis adjusted by comorbidities, cardiovascular drugs and healthcare utilization was performed. RESULTS In various multivariate models, the use of inhaled long-acting muscarinic antagonists (LAMAs) or long-acting inhaled β2 agonists (LABAs) was significantly associated with tachyarrhythmias. Statistically significant effects of LAMAs on tachyarrhythmias were found only in the non-users of β-blockers. We did not find a statistically significant difference in the impact of a LABA without a LAMA vs a LAMA without a LABA (aOR, 0.93; 95% CI, 0.74-1.18), or a multiplicative or additive interaction between a LABA and a LAMA. CONCLUSIONS Inhaled LAMAs and LABAs were significantly and comparably associated with an increased risk of tachyarrhythmias.

Development of a Korean Fracture Risk Score (KFRS) for Predicting Osteoporotic Fracture Risk: Analysis of Data from the Korean National Health Insurance Service.

Background Asian-specific prediction models for estimating individual risk of osteoporotic fractures are rare. We developed a Korean fracture risk prediction model using clinical risk factors and assessed validity of the final model. Methods A total of 718,306 Korean men and women aged 50–90 years were followed for 7 years in a national system-based cohort study. In total, 50% of the subjects were assigned randomly to the development dataset and 50% were assigned to the validation dataset. Clinical risk factors for osteoporotic fracture were assessed at the biennial health check. Data on osteoporotic fractures during the follow-up period were identified by ICD-10 codes and the nationwide database of the National Health Insurance Service (NHIS). Results During the follow-up period, 19,840 osteoporotic fractures were reported (4,889 in men and 14,951 in women) in the development dataset. The assessment tool called the Korean Fracture Risk Score (KFRS) is comprised of a set of nine variables, including age, body mass index, recent fragility fracture, current smoking, high alcohol intake, lack of regular exercise, recent use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis. The KFRS predicted osteoporotic fractures over the 7 years. This score was validated using an independent dataset. A close relationship with overall fracture rate was observed when we compared the mean predicted scores after applying the KFRS with the observed risks after 7 years within each 10th of predicted risk. Conclusion We developed a Korean specific prediction model for osteoporotic fractures. The KFRS was able to predict risk of fracture in the primary population without bone mineral density testing and is therefore suitable for use in both clinical setting and self-assessment. The website is available at http://www.nhis.or.kr.

Risk of hospital admission or emergency room visit for pneumonia in patients using respiratory inhalers: A case-crossover study

The impact of inhaled corticosteroid (ICS) use on the development of pneumonia has been heavily debated. The aim of this study was to elucidate the association between the use of inhalers, including ICS, and a hospital admission or an emergency room (ER) visit for pneumonia.

Epidemiology of Hip Replacements in Korea from 2007 to 2011

We analyzed national data collected by the Health Insurance Review and Assessment Service in Korea from 2007 to 2011; 1) to document procedural numbers and procedural rate of bipolar hemiarthroplasty (BH), primary and revision total hip arthroplasties (THAs), 2) to stratify the prevalence of each procedure by age, gender, and hospital type, and quantified, 3) to estimate the revision burden and evaluate whether the burden is changed over time. Our final study population included 60,230 BHs, 40,760 primary THAs, and 10,341 revision THAs. From 2007 to 2011, both the number and the rate of BHs, primary THAs increased steadily, whereas there was no significant change in revision THAs. Over the 5 yr, the rate of BHs and primary THAs per 100,000 persons significantly increased by 33.2% and 21.4%, respectively. The number of revision THAs was consistent over time. The overall annual revision burden for THA decreased from 22.1% in 2007 to 18.9% in 2011. In contrast to western data, there were no changes in the number and rate of revision THAs, and the rates of primary and revision THAs were higher for men than those for women. Although 5 yr is a short time to determine a change in the revision burden, there have been significant decreases in some age groups. Graphical Abstract

Efficacy of Treatment for Latent Tuberculosis in Patients Undergoing Treatment with a Tumor Necrosis Factor Antagonist

Rationale: Current guidelines recommend that all patients undergoing treatment with a tumor necrosis factor‐&agr; antagonist should receive screening for latent tuberculosis and appropriate treatment before initiating the inhibitor. However, no well‐designed study has shown the efficacy of treating these patients for latent tuberculosis. Objectives: To compare the risk of active tuberculosis between tumor necrosis factor antagonist users who have received treatment for latent tuberculosis with those who have not. Methods: We performed a national‐level retrospective cohort study in South Korea, a country with an intermediate tuberculosis burden, by analyzing claims recorded between January 1, 2011, and December 31, 2013, in an obligatory national health insurance claims database. The primary outcome, the incidence of active tuberculosis, was measured as the occurrence of an International Statistical Classification of Diseases and Related Health Problems, 10th edition, diagnosis of tuberculosis and prescription of at least two antituberculosis drugs at least twice within 90 days. Results: Among 10,863 eligible new tumor necrosis factor antagonist users, 2,461 (22.7%) received treatment for latent tuberculosis. The incidence rate of tuberculosis per 1,000 person‐years was lower for the treated group (4.07; 95% confidence interval [CI], 1.55‐6.60) than for the untreated group (12.34; 95% CI, 9.96‐14.72). The risk for tuberculosis was significantly reduced by preventive chemotherapy (incidence rate ratio, 0.33; 95% CI, 0.17‐0.63). Conclusions: Treatment for latent tuberculosis was highly effective in preventing the development of tuberculosis among tumor necrosis factor antagonist users.

Osteoporotic Fracture Risk Assessment Using Bone Mineral Density in Korean: A Community-based Cohort Study

Background Fracture-risk assessment tool (FRAX) using just clinical risk factors of osteoporosis has been developed to estimate individual risk of osteoporotic fractures. We developed prediction model of fracture risk using bone mineral density (BMD) as well as clinical risk factors in Korean, and assessed the validity of the final model. Methods To develop and validate an osteoporotic FRAX, a total of 768 Korean men and women aged 50 to 90 years were followed for 7 years in a community-based cohort study. BMD as well as clinical risk factors for osteoporotic fracture including age, sex, body mass index, history of fragility fracture, family history of fracture, smoking status, alcohol intake, use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis were assessed biannually. Results During the follow-up period, 86 osteoporotic fractures identified (36 in men and 50 in women). The developed prediction models showed high discriminatory power and had goodness of fit. Conclusions The developed a Korean specific prediction model for osteoporotic fractures can be easily used as a screening tool to identify individual with high risk of osteoporotic fracture. Further studies for validation are required to confirm the clinical feasibility in general Korean population.

The efficacy and safety of triple inhaled treatment in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis using Bayesian methods

Purpose Although tiotropium (TIO) and inhaled corticosteroid (ICS)/long-acting β-agonists are frequently prescribed together, the efficacy of “triple therapy” has not been scientifically demonstrated. We conducted a systematic review and meta-analysis using Bayesian methods to compare triple therapy and TIO monotherapy. Methods We searched the MEDLINE, EMBASE, and Cochrane Library databases for randomized controlled trials comparing the efficacy and safety of triple therapy and TIO monotherapy in patients with chronic obstructive pulmonary disease (COPD). We conducted a meta-analysis to compare the effectiveness and safety of triple therapy and TIO monotherapy using Bayesian random effects models. Results Seven trials were included, and the risk of bias in the majority of the studies was acceptable. There were no statistically significant differences in the incidence of death and acute exacerbation of disease in the triple therapy and TIO monotherapy groups. Triple therapy improved the prebronchodilator forced expiratory volume in 1 second (mean difference [MD], 63.68 mL; 95% credible interval [CrI], 45.29–82.73), and patients receiving triple therapy showed more improvement in St George Respiratory Questionnaire scores (MD, −3.11 points; 95% CrI, −6.00 to −0.80) than patients receiving TIO monotherapy. However, both of these differences were lower than the minimal clinically important difference (MCID). No excessive adverse effects were reported in triple therapy group. Conclusion Triple therapy with TIO and ICSs/long-acting β-agonists was only slightly more efficacious than TIO monotherapy in treating patients with COPD. Further investigations into the efficacy of new inhaled drugs are needed.

Glucocorticoids Are Associated with an Increased Risk for Vertebral Fracture in Patients with Rheumatoid Arthritis

Objective. To identify the effects of glucocorticoids (GC) on various types of fractures in patients with rheumatoid arthritis (RA). Methods. We used the Korean National Healthcare Claims database from 2010 to establish a retrospective cohort of patients with RA ≥ 19 years old. We then followed those patients through December 2013. The incidence rates of total and major fractures were calculated. We evaluated the effects of GC dose and duration on fractures using multivariable logistic regression analyses. We also examined the influence of GC on fractures in RA patients without a history of osteoporosis. Results. A total of 11,599 fractures was observed in 9964 out of 138,240 patients with RA. During followup, 68.2% of patients used oral GC for > 3 months. Adjusted analysis showed the risk of vertebral fractures was increased by the following characteristics: duration of GC ≥ 6 months (OR 1.76, p < 0.01); mean dose of GC ≥ 2.5 mg (OR range = 1.37–1.71, p < 0.01); and highest daily dose of GC ≥ 10 mg (OR range = 1.23–1.75, p < 0.03). However, neither the duration nor the dose of oral GC increased the risk of hip and nonvertebral/nonhip fractures in patients with RA. Consistent results were observed in RA patients without osteoporosis. Conclusion. Longer duration and higher dose of oral GC in patients with RA increased the risk of vertebral fractures. However, the dose and duration of GC did not influence the risk of hip and nonvertebral/nonhip fractures.