Ju-Young Shin

Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study.

Objective To determine whether treatment with methylphenidate in children and young people with attention-deficit/hyperactivity disorder (ADHD) was associated with cardiovascular events. Design Self controlled case series analysis. Setting Nationwide health insurance database, 1 January 2008 to 31 December 2011, in South Korea. Participants 1224 patients aged ≤17 who had experienced an incident cardiovascular event and had had at least one incident prescription for methylphenidate. Main outcome measures A recorded diagnosis (either a primary or secondary cause) of any of the following cardiovascular adverse events: arrhythmias (ICD-10 (international classification of diseases, 10th revision) codes I44, I45, I47, I48, I49), hypertension (codes I10-I15), myocardial infarction (code I21), ischemic stroke (code I63), or heart failure (code I50). Incidence rate ratios were calculated with conditional Poisson regression and adjusted for time varying comorbidity and comedication. Results Increased risk of arrhythmia was observed in all exposed time periods—that is, periods of treatment with methylphenidate—(incidence rate ratio 1.61, 95% confidence interval 1.48 to 1.74), and the risk was highest in the children who had congenital heart disease. No significant risk of myocardial infarction was observed for all exposed time periods (1.33, 0.90 to 1.98), though risk was higher in the early risk periods between eight and 56 days after the start of treatment with methylphenidate. No significant increased risk was observed for hypertension, ischemic stroke, or heart failure. Conclusion The relative risk of myocardial infarction and arrhythmias is increased in the early period after the start of methylphenidate treatment for ADHD in children and young people. Though the absolute risk is likely to be low, the risk-benefit balance of methylphenidate should be carefully considered, particularly in children with mild ADHD.

Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis

ABSTRACT Objective: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest. Results: 54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation. Conclusion: Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.

Comparative safety for cardiovascular outcomes of DPP-4 inhibitors versus glimepiride in patients with type 2 diabetes: A retrospective cohort study

Abstract Concerns about the cardiovascular safety of dipeptidyl peptidase-4 (DPP-4) inhibitors persist. This study sought to determine whether there is a differential risk of hospitalization for cardiovascular diseases (CVDs) between DPP-4 inhibitors and glimepiride. We conducted this retrospective cohort study by using the Korean National Health Insurance Service database from December 1, 2008, to December 31, 2013. The study subjects were new users of DPP-4 inhibitors or glimepiride for type 2 diabetes. Outcome was defined as hospitalization for CVDs, including angina pectoris, myocardial infarction, transient cerebral ischemic attack, heart failure, or cerebrovascular disease or any procedure involving coronary artery bypass grafting or percutaneous coronary intervention. We used a Cox proportional hazard model to estimate the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs), to assess the risk of CVDs associated with the use of DPP-4 inhibitors compared with glimepiride. The cohort consisted of 1,045,975 patients, with 6504 in the DPP-4 inhibitors group and 13,447 in the glimepiride group. No significant increased risk of total CVDs was found (aHR, 0.87; 95% CI, 0.75–1.01) in the DPP-4 inhibitors versus glimepiride group. A decreased risk of hospitalization for CVDs was found among patients with a history of visit for CVDs (aHR, 0.73; 95% CI, 0.56–0.97) or with >2.5 years’ duration of type 2 diabetes (aHR, 0.77; 95% CI, 0.66–0.91) in the DPP-4 inhibitors versus glimepiride group. DPP-4 inhibitors did not increase cardiovascular risk compared with glimepiride regardless of CVD history and diabetes duration.

Health Care Utilization and Direct Costs in Mild, Moderate, and Severe Adult Asthma: A Descriptive Study Using the 2014 South Korean Health Insurance Database

PURPOSEnAlthough asthma exacerbation comprises a large burden of the total asthma-related costs, few studies have examined the frequency and cost of acute exacerbation according to asthma severity. This study investigated asthma-related health care utilization and costs according to the severity of asthma.nnnMETHODSnWe conducted a descriptive study using the national health insurance claims database between January 1 and December 31, 2014. We included adult patients with asthma (18 years of age and older) who had ≥2 claims with for an asthma diagnosis and were prescribed ≥1 asthma medications. They were classified into 3 asthma severity levels (level 1 = mild, level 2 = moderate, and level 3 = severe), based on individual medication prescriptions. Acute exacerbation was defined as having a corticosteroid burst, an emergency department visit, or hospitalization. Health care utilization, acute exacerbation, and direct costs associated with asthma were compared according to asthma severity levels.nnnFINDINGSnOf the 36,687 adult asthma patients, level 1 had the largest proportion of patients (81.2%), followed by level 2 (18.2%), and level 3 (0.6%). The average number of asthma-related outpatient visits was 4.5 for level 1, 7.2 for level 2, and 11.9 for level 3 (P < 0.01). The estimated asthma-related direct cost per patient was

Trends in prescription of pregnancy-contraindicated drugs in Korea, 2007–2011

174 for level 1,

Prescribing patterns for attention deficit hyperactivity disorder medications among children and adolescents in Korea, 2007-2011.

634 for level 2, and

The Uncertainty of the Association Between Proton Pump Inhibitor Use and the Risk of Dementia: Prescription Sequence Symmetry Analysis Using a Korean Healthcare Database Between 2002 and 2013

1635 for level 3 (P < 0.01). The number of patients who experienced acute exacerbation increased as asthma severity increased: level 1, 22.6%; level 2, 26.0%; and level 3, 48.7% (P < 0.01). Direct costs associated with asthma exacerbation dramatically increased and accounted for 15.1% of the total cost in level 1 patients, 19.5% in level 2 patients, and 40.8% in level 3 patients (P < 0.01).nnnIMPLICATIONSnThe direct costs of acute exacerbation increased as asthma severity increased. In patients with severe asthma, acute exacerbation and the relative cost ratio in South Korea were higher than those in other countries. Proper management is required to avoid acute exacerbations and to reduce the burden of asthma, particularly in patients with severe asthma.

Decrease in use of contraindicated drugs with automated alerts in children

This study aims to evaluate changes in use of contraindicated drugs during pregnancy in Korea using the nationwide Health Insurance and Assessment Service (HIRA) database. Study drugs were 314 drugs that were announced as pregnancy-contraindicated on December 11, 2008. The study population consisted of the pregnant women who gave birth and were prescribed any of the drugs in 2007-2011 before giving birth. Pregnancy-contraindicated drug use was defined as the proportion of prescriptions among pregnant women that were for study drugs. The relative and absolute reductions in contraindicated drug use after the 2008 action were estimated with 95% confidence interval (CI) by medical institution type, region, and drug class. The predicted monthly contraindicated drug use was estimated by performing ordinary least-squares regression analysis of data before the action and compared with observed data after the action. Between 2007 and 2011, a total of 1,468,588 pregnant women received 1,796,208 prescriptions. Contraindicated drug use accounted for 15.96% of total prescriptions (Nxa0=xa0355,783) before the action but decreased to 11.52% (Nxa0=xa0453,832) afterward. Overall, the relative reduction was 27.77% (95% CI: 27.64%-27.90%) and greatest for hormones at 46.56% (95% CI: 46.21%-46.93%). The relative reduction was 55.43% (95% CI: 54.60%-55.43%) for all category X drugs, 17.09% (95% CI: 16.46%-17.75%) for category X drugs excluding hormones, and 0.14% (95% CI: 0.14%-0.15%) for category D drugs including hormones. A regulatory action toward pregnancy-contraindicated drugs led to moderate decrease in contraindicated drug use during pregnancy. Despite the decreases, contraindicated drugs were still widely prescribed to pregnant women, highlighting the need to develop strategies to assess and improve drug safety during pregnancy.

Comparison of Effectiveness Between Delamanid and Bedaquiline Among Patients with Multidrug-Resistant Tuberculosis: A Markov Model Simulation Study

ObjectivesnThis study analyzed the prevalence of attention deficit hyperactivity disorder (ADHD) medication users among children and adolescents in Korea between January 1, 2007 and December 31, 2011.nnnMethodsnUsing the Korea National Health Insurance claims database, we identified the patients aged between 1 and 17 years who had at least one medical claim for the diagnosis of ADHD (ICD-10: F90.0). The annual prevalence of ADHD diagnosis was calculated, using national census data from the Statistics Korea on the population aged between 1 and 17 years as the denominator. The prevalence was age-standardized using 2010 population as the standard population. The number of patients who were treated with either methylphenidate or atomoxetine and the prevalence of total patients with ADHD that were treated with either drug were also calculated for each year. All analyses were performed by gender and age group (1-5y, 6-12y, and 13-17y).nnnResultsnThe number of patients diagnosed with ADHD increased from 72,704 persons (0.71%) in 2007 to 85,468 persons (0.93%) in 2011. The annual age-standardized prevalence of ADHD diagnosis increased from increased from 0.67% in 2007 to 0.94% in 2011. The prevalence of methylphenidate users decreased from 73.91% in 2007 to 70.33% in 2011 whereas that of atomoxetine users increased from 5.77% in 2009 to 13.09% in 2011.nnnConclusionnWhile methylphenidate remains the most commonly prescribed ADHD drug, use of atomoxetine has increased.OBJECTIVES This study analyzed the prevalence of attention deficit hyperactivity disorder (ADHD) medication use among children and adolescents in Korea between January 1, 2007 and December 31, 2011. METHODS Using the Korea National Health Insurance claims database, we identified patients between one and 17 years of age who had at least one medical claim for the diagnosis of ADHD (International Classification of Diseases, 10th revision: F90.0). The annual prevalence of ADHD diagnoses was calculated, using national census data from Statistics Korea on the population aged between one and 17 years as the denominator. The prevalence was age-standardized using the 2010 population as the standard population. The number of patients who were treated with methylphenidate and/or atomoxetine and the prevalence of total patients with ADHD that were treated with either drug were also calculated for each year. All analyses were stratified according to gender and age group (1-5 years, 6-12 years, and 13-17 years). RESULTS The number of patients diagnosed with ADHD increased from 72,704 persons (0.71%) in 2007 to 85,468 persons (0.93%) in 2011. The annual age-standardized prevalence of ADHD diagnoses increased from 0.67% in 2007 to 0.94% in 2011. The prevalence of methylphenidate use among children and adolescents with ADHD decreased from 73.91% in 2007 to 70.33% in 2011, whereas that of atomoxetine use increased from 5.77% in 2009 to 13.09% in 2011. CONCLUSIONS While methylphenidate remains the most commonly prescribed ADHD drug, the use of atomoxetine has increased.

Quantifying Children's Engagement with Educational Tangible Blocks

IntroductionStudies have found an association between the use of proton pump inhibitors (PPIs) and dementia, but these findings may have been confounded by selection biases.ObjectiveWe used prescription sequence symmetry analysis (PSSA) to estimate the sequence ratio (SR) between PPI use and dementia compared with an active comparator, the use of histamine-2 receptor antagonists (H2RAs).MethodsWe conducted a PSSA on a nationwide South Korean database between 2002 and 2013. Exposure was defined as new PPI users, and outcome was defined as a new dementia diagnosis (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] codes F00-03, F05.1, G30, G31.1, G31.9, G31.82). In this study, we applied the 3-year time window. So the patients who initiated PPIs 3 years before or after their first diagnosis of dementia were included. The pairs with the time window <xa06 months were excluded to minimize the potential protopathic bias. The SR was calculated as the number of patients first diagnosed with dementia after initiating PPI (causal group) divided by the number of patients first diagnosed with dementia before the initiation of PPI (non-causal group). The SR was adjusted (aSR) to avoid the distortion of results due to underlying trends in PPI use and dementia diagnosis over time. We calculated 95% confidence intervals (CIs) for the aSR. The analysis was repeated for initiators of H2RAs. Sensitivity analyses were conducted using 1-, 2-, and 6-year time windows and using the initiation of medication for dementia treatment (Anatomical Therapeutic Chemical code: N06D).ResultsOur results showed that the aSR of dementia and PPIs (7342 pairs, aSR 1.21 [95% CI 1.16–1.27]) was not higher than that for dementia and H2RAs (6170 pairs, aSR 1.91 [95% CI 1.80–2.02]). When we used various time windows and restricted the findings to the use of medication for treating dementia, the results were consistent with the main results.ConclusionThe risk of PPIs being associated with dementia may be overestimated. Further pharmacoepidemiological studies are needed to identify the risk of dementia with PPI use.