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  • Air pollution mixture associated with oxidative stress exacerbation and symptoms deterioration in allergic rhinitis patients: Evidence from a panel study. The Science of the total environment Li, J., Wu, H., Xing, W., Li, X., Han, Z., Ji, R., Deng, Z., Jung, M., Sun, S., Chung, B. I., Cardenas, A., Langston, M. E. 2024: 172688


    With allergic rhinitis (AR) on the rise globally, there has been a growing focus on the role of environmental pollutants in the onset of AR. However, the potential mechanisms by how and which these pollutants exacerbate AR conditions remain unknown. This panel study of 49 patients diagnosed with AR over one year aimed to assess the individual and combined effects of short-term exposure to multiple ambient pollutants on oxidative stress, symptoms, and quality of life among patients with AR. All participants underwent four repeated assessments of health conditions and personal environmental exposures (PM2.5, O3, SO2, and NO2) over warm and cold seasons during 2017-2018. We evaluated two oxidative stress biomarkers (malondialdehyde [MDA], and superoxide dismutase [SOD]) via nasal lavage. We collected information on self-reported symptoms and quality of life using the Rhinitis Symptom Scale (SRS), the Visual Analog Scale (VAS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) through in-person interviews. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effects of pollutant mixture and identify key contributors. The results revealed a significant association of the pollutant mixture when all four pollutants were at or above their median levels, with increased oxidative stress. This was evidenced by elevated MDA and reduced SOD. We found a joint detrimental effect of the pollutant mixture on AR symptoms with a strong association with increased SRS scores, but a non-significant positive association with VAS and RQLQ scores. PM2.5, O3, and SO2 presented as the potentially primary contributors to the adverse health effects associated with the pollutant mixture in Taiyuan city. Patients with AR exposed to short-term air pollutant mixture are more likely to have greater nasal symptoms and worse quality of life from increased oxidative stress and reduced antioxidant capacity. Further research is warranted to better elucidate the underlying mechanisms.

    View details for DOI 10.1016/j.scitotenv.2024.172688

    View details for PubMedID 38663627

  • Low-Intensity Statin Plus Ezetimibe Versus Moderate-Intensity Statin for Primary Prevention: A Population-Based Retrospective Cohort Study in Asian Population. The Annals of pharmacotherapy Jung, M., Lee, B. J., Lee, S., Shin, J. 2024: 10600280241237781


    While moderate-intensity statin therapy is recommended for primary prevention, statins may not be utilized at a recommended intensity due to dose-dependent adverse events, especially in an Asian population. However, evidence supporting the use of low-intensity statins in primary prevention is limited.We sought to compare clinical outcomes between a low-intensity statin plus ezetimibe and a moderate-intensity statin for primary prevention.This population-based retrospective cohort study used the Korean nationwide claims database (2002-2019). We included adults without atherosclerotic cardiovascular diseases who received moderate-intensity statins or low-intensity statins plus ezetimibe. The primary outcome was a composite of all-cause mortality, myocardial infarction, and ischemic stroke. The safety outcomes were liver and muscle injuries and new-onset diabetes mellitus (DM). We used standardized inverse probability of treatment weighting (sIPTW) and propensity score matching (PSM).In the sIPTW model, 1717 and 36 683 patients used a low-intensity statin plus ezetimibe and a moderate-intensity statin, respectively. In the PSM model, each group included 1687 patients. Compared with moderate-intensity statin use, low-intensity statin plus ezetimibe use showed similar risks of the primary outcome (hazard ratio [HR] = 0.92, 95% CI = 0.81-1.12 in sIPTW and HR = 1.16, 95% CI = 0.87-1.56 in PSM model). Low-intensity statin plus ezetimibe use was associated with decreased risks of liver and muscle injuries (subHR [sHR] = 0.84, 95% CI = 0.74-0.96 and sHR = 0.87, 95% CI = 0.77-0.97 in sIPTW; sHR = 0.84, 95% CI = 0.72, 0.96 and sHR = 0.82, 95% CI = 0.72-0.94 in PSM model, respectively). For new-onset DM and hospitalization of liver and muscle injuries, no difference was observed.Low-intensity statin plus ezetimibe may be an alternative to moderate-intensity statin for primary prevention. Our findings provide evidence on safety and efficacy of statin therapy in Asian population.

    View details for DOI 10.1177/10600280241237781

    View details for PubMedID 38506414

  • Clinical outcomes and predictors of a gap in direct-acting oral anticoagulant therapy in the elderly: A time-varying analysis of a nationwide cohort study. Thrombosis research Jung, M., Lee, B. J., Lee, S., Shin, J. 2023; 226: 61-68


    As direct-acting oral anticoagulants (DOACs) have short half-lives of around 12 h, even a short gap in DOAC therapy may diminish anticoagulation effects, increasing risks of adverse clinical outcomes. We aimed to evaluate clinical consequences of a gap in DOAC therapy with atrial fibrillation (AF) and to identify its potential predictors.In this retrospective cohort study, we included DOAC users aged over 65 years with AF from the 2018 Korean nationwide claims database. We defined a gap in DOAC therapy as no claim for a DOAC one or more days after the due date of a refill prescription. We used a time-varying-analysis method. The primary outcome was a composite of death and thrombotic events including ischemic stroke/transient ischemic attack or systemic embolism. Potential predictors of a gap included sociodemographic and clinical factors.Among 11,042 DOAC users, 4857 (44.0 %) patients had at least one gap. Standard national health insurance, non-metropolitan locations of medical institutions, history of liver disease, chronic obstructive pulmonary disease, cancer, or dementia, and use of diuretics or non-oral agents were associated with increased risks of a gap. In contrast, history of hypertension, ischemic heart disease, or dyslipidemia were associated with a decreased risk of a gap. A short gap in DOAC therapy was significantly associated with a higher risk of the primary outcome compared to no gap (hazard ratio 4.04, 95 % confidence interval 2.95-5.52). The predictors could be utilized to identify at-risk patients to provide additional support to prevent a gap.

    View details for DOI 10.1016/j.thromres.2023.04.018

    View details for PubMedID 37121013

  • A comparison of methods for the measurement of adherence to antihypertensive multidrug therapy and the clinical consequences: a retrospective cohort study using the Korean nationwide claims database. Epidemiology and health Jung, M., Choo, E., Lee, S. 2023: e2023050


    Objectives: In observational studies, the mehtods used to measure medication adherence may affect assessments of the clinical outcomes of drug therapy. This study estimated medication adherence to multidrug therapy in patients with hypertension using different measurement methods and compared their impacts on clinical outcomes.Methods: This was a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort database (2006-2015). Adults diagnosed with hypertension who initiated multidrug antihypertensive therapy in the index year 2007 were included. Adherence was defined as over 80% compliance. Adherence to multidrug antihypertensive therapy was measured in 3 ways using the proportion of days covered (PDC) with 2 approaches to the end-date of the study observations: PDC with at least one drug (PDCwith≥1), PDC with a duration weighted mean (PDCwm), and the daily polypharmacy possession ratio (DPPR). The primary clinical outcome was a composite of cardiovascular and cerebrovascular disease-specific hospitalizations or all-cause mortality.Results: In total, 4,226 patients who initiated multidrug therapy for hypertension were identified. The mean adherence according to the predefined measurements varied from 72.7% to 79.8%. Non-adherence was associated with an increased risk of a primary outcome. The hazard ratios (95% confidence intervals) primary outcomes varied from 1.38 (1.19-1.59) to 1.44 (1.25-1.67).Conclusion: Non-adherence to multidrug antihypertensive therapy was significantly associated with an increased risk of a primary clinical outcome. Across the varying estimates based on different methods medication adherence levels were similar. These findings may provide evidence to support decision-making when assessing medication adherence.

    View details for DOI 10.4178/epih.e2023050

    View details for PubMedID 37139667

  • Comparing the Sensitivities of Measures of Adherence to Antihypertensive Drugs Using Korean National Health Insurance Claims Data. Patient preference and adherence Choo, E., Jung, M., Shin, J., Lee, S. 2021; 15: 1717-1728


    Numerous studies have utilized various forms of adherence measures. However, methods for measuring adherence are inconsistent. Moreover, few studies are available that have compared sensitivities of the effects of several criteria on medication adherence. This study aims to compare measures of adherence using varied analytical decisions.We included three measures for adherence: proportion of days covered with one or more medications (PDCwith≥1), duration weighted mean PDC (PDCwm), and daily polypharmacy possession ratio (DPPR). We compared the sensitivities of the measures by changing parameters in the Korean nationwide claims database. First, we used PDCwith≥1 as our base model. Then, we divided an adherence measure algorithm into three categories: (1) definition of data cleaning, (2) inclusion criteria and observation period, and (3) calculation methods of medication adherence. The categories included eight decision nodes that incorporated 25 alternative options. Finally, we assessed the medication adherence for the base-case with commonly used values and then varied to measure with each alternative option.The base-case included 14,288 beneficiaries with antihypertensives. Among eight decisions, both handling an end-date-of-study and overlaps had the strongest impacts on measuring PDCwith≥1, PDCwm, and DPPR, with small differences in sample size. Instead of the estimates of adherence from PDCwm, those of PDCwith≥1 and DPPR were similar. Furthermore, a tendency toward a higher medication adherence was observed with a smaller study population.The decisions regarding identifying an end-date-of-study and overlaps showed meaningful impacts of all three measures including PDCwith≥1, PDCwm, and DPPR on measuring medication adherence.

    View details for DOI 10.2147/PPA.S322745

    View details for PubMedID 34408405

    View details for PubMedCentralID PMC8360770

  • Comprehensive Trends and Patterns of Antihypertensive Prescriptions Using a Nationwide Claims Database in Korea. Clinical epidemiology Jung, M., Choo, E., Lee, S. 2020; 12: 963-975


    The number of people receiving antihypertensive prescriptions in Korea has increased more than threefold from 2002 to 2016. However, previous studies regarding the current use of these medications have been fairly limited. We aimed to examine the current trends and changes in the patterns of antihypertensive prescriptions based on a nationwide claims database.Patients receiving antihypertensive medications over 30 days, without any limited therapeutic indication, were identified using the Health Insurance Review and Assessment Service (HIRA) database between 2015 and 2017. For each patient, the use of antihypertensive medication was specified as the class of drug used for the longest duration in each year.A total of 8,625,821 patients in 2015, 8,997,829 patients in 2016, and 9,357,751 patients in 2017 taking antihypertensives were included in this study. Angiotensin II receptor blockers (ARB) (35.9% in 2015 and 38.9% in 2017) and calcium channel blockers (CCB) (37.1% in 2015 and 35.2% in 2017) for monotherapy, ARB+CCB combinations (49.3% in 2015 and 56.3% in 2017) for dual therapy, and ARB+CCB+diuretics combinations (48.8% in 2015 and 48.9% in 2017) for more than triple therapy were the most frequently prescribed. Subjects aged ≥70 showed the highest prescription rate of antihypertensives compared with those <70; however, a decreasing trend presented from 62.3% in 2015 to 54.2% in 2017. Additionally, in subjects aged >70 years, the rate in women was higher than that in men, but this was reversed in younger patients. While changes arose in the patterns of the use of antihypertensives, these were similar each year.The trends and changes in the patterns of the use of antihypertensive medications were affected by age, sex, and type of therapy. Our findings may contribute to a better understanding of the actual status regarding the use of antihypertensive medications in Korea.

    View details for DOI 10.2147/CLEP.S265966

    View details for PubMedID 32982461

    View details for PubMedCentralID PMC7494009

  • Impact of Statin Use on Dementia Incidence in Elderly Men and Women with Ischemic Heart Disease. Biomedicines Kim, M. Y., Jung, M., Noh, Y., Shin, S., Hong, C. H., Lee, S., Jung, Y. S. 2020; 8 (2)


    This study aimed to determine the association between statins and the prevention of dementia according to sex differences in elderly patients with ischemic heart disease (IHD). We performed a nationwide retrospective cohort study using the Korean Health Insurance Review and Assessment Service database (2007-2015). Among the 264,036 eligible patients aged ≥65 years with IHD, statin users were compared with non-users by propensity score matching at a 1:1 ratio (71,587 in each group). The primary outcome was dementia risk by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Differential risks of dementia were assessed by sex in the subgroups of statin types, exposure duration, and patient age, implying that sex is an influential factor for the link between statin use and dementia incidence. Among seven commonly prescribed statins, rosuvastatin was associated with the greatest preventive effect on dementia incidence, with an adjusted HR of 0.82 (95% CI = 0.78-0.87). In a subgroup analysis organized by sex, the differential risk of dementia incidence was assessed in each statin group, implying that sex is an influential factor for the link between statin and dementia. This study suggests that appropriate statin use considering sex differences may have beneficial effects on the development of dementia.

    View details for DOI 10.3390/biomedicines8020030

    View details for PubMedID 32050497

    View details for PubMedCentralID PMC7168191

  • Efficacy of Aspirin in the Primary Prevention of Cardiovascular Diseases and Cancer in the Elderly: A Population-Based Cohort Study in Korea. Drugs & aging Jung, M., Lee, S. 2020; 37 (1): 43-55


    Aspirin is widely used to prevent cardiovascular diseases (CVDs). However, the balance of its benefits and risks in the primary prevention of CVDs and cancer is unclear, especially in elderly Asians. The present study aimed to evaluate the efficacy of aspirin in the primary prevention of major adverse cardiac and cerebrovascular events (MACCE), bleeding risk, and cancer in elderly Koreans with cardiovascular (CV) risk factors.This retrospective cohort study used data from the Korean National Health Insurance Service-Senior cohort database (2002-2015). Patients aged 60-90 years with hypertension, type 2 diabetes mellitus (T2DM), or dyslipidemia were identified. Aspirin users were compared with non-users using propensity score matching at a 1:3 ratio. The primary outcome was MACCE, a composite of CV mortality, myocardial infarction, and ischemic stroke. The secondary outcomes were the components of MACCE, all-cause mortality, angina pectoris, heart failure, the incidence and mortality of cancer, and the risks of hemorrhagic stroke and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazard model.A total of 3366 aspirin users and 10,089 non-users were finally included in the study. During a mean follow-up of 7.8 years, the incidence of MACCE was 15.2% in aspirin users and 22.4% in non-users. The risk of MACCE was significantly lower in aspirin users than in non-users (HR 0.76; 95% CI 0.69-0.85), and this risk was significantly reduced in patients using aspirin over 5 years (HR 0.52; 95% CI 0.46-0.60). Aspirin use was associated with a 21% reduction in the risk of primary cancer (HR 0.79; 95% CI 0.70-0.88) and cancer-related mortality (HR 0.72; 95% CI 0.61-0.84). No significant differences in bleeding risks were observed between the two groups.Aspirin reduced the risks of MACCE and cancer without increasing the bleeding risk in elderly Koreans with hypertension, T2DM, or dyslipidemia. Moreover, the benefits of the long-term use of aspirin in reducing the risks of MACCE were demonstrated. However, the decision of using aspirin for primary prevention must be carefully made on an individual basis, while estimating the benefit-risk balance of aspirin.

    View details for DOI 10.1007/s40266-019-00723-3

    View details for PubMedID 31755069

  • Effects of Statin Therapy on the Risk of Intracerebral Hemorrhage in Korean Patients with Hyperlipidemia. Pharmacotherapy Jung, M., Lee, S. 2019; 39 (2): 129-139


    Statins are widely used for primary and secondary prevention of cardiovascular and cerebrovascular disease. Several large randomized trials have suggested that statins might increase the risk of intracerebral hemorrhage (ICH); studies have also shown interethnic variability in responses to statins. This study aimed to determine the association between statin use and the risk of ICH in patients with hyperlipidemia among a Korean population.Population-based, retrospective cohort study.Korean National Health Insurance Service-National Sample Cohort database (2002-2015).A total of 313,368 patients, aged 40-85 years, without a history of hemorrhagic stroke were included after being diagnosed with hyperlipidemia between January 2003 and December 2013 (for follow-up through December 2015). Of those, statin users were compared with nonusers by using propensity score matching in a 1:1 ratio (21,797 in each group). The study groups were matched for age, sex, Charlson Comorbidity Index score, follow-up duration, comorbidities, and concurrent medications.The primary endpoint was occurrence of an ICH event. Secondary endpoints were mortality (all-cause, major adverse cardiovascular and cerebrovascular event related, and stroke related) and outcomes after ICH (e.g., recurrent ICH and mortality after primary ICH event). The Cox proportional hazard model was used to evaluate the ICH risk of statins. Subgroup analyses were performed based on ICH-related risk factors. During a mean follow-up period of 6.4 years, ICH occurred in 456 of the 43,594 patients (1.05%). Statin use was significantly associated with a decreased ICH risk (adjusted hazard ratio [aHR] 0.78, 95% confidence interval [CI] 0.65-0.94). Compared with nonusers, statin users showed significantly lower all-cause mortality (aHR 0.61, 95% CI 0.57-0.64), cardiovascular and cerebrovascular disease-related mortality (aHR 0.75, 95% CI 0.65-0.85), and stroke-related mortality (aHR 0.69, 95% CI 0.54-0.88). No significant differences in recurrence and mortality after an ICH event were noted between study groups.Statin therapy was associated with a decreased ICH risk and improvements in ischemic cardiovascular and cerebrovascular outcomes in Korean patients with hyperlipidemia. Further large-scale clinical studies are needed to clarify the impact of statins on the risk of developing ICH.

    View details for DOI 10.1002/phar.2211

    View details for PubMedID 30585646