Safety of BNT162b2 mRNA COVID-19 vaccine in children with chronic kidney disease: a national population study from South Korea.

BACKGROUND: In South Korea, COVID-19 vaccination has been recommended to adolescents aged 12 - 17 since October, 2021. We aimed to assess the rate of adverse events following COVID-19 vaccination in adolescents with chronic kidney disease (CKD) in South Korea, using national cohort data. METHODS: We retrieved the clinical information of adolescents 12 - 17 years old from the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service (K-COV-N) database, to calculate incidence rates of purpura and other hemorrhagic conditions, Guillain-Barré syndrome (GBS), Kawasaki disease/multisystem inflammatory syndrome in children (MIS-C), myocarditis and/or pericarditis, and anaphylaxis in adolescents with CKD, after BNT162b2 vaccination. RESULTS: Among the 2306 adolescents with CKD, 62.7% (n = 1446) had received the BNT-162b2 vaccine. GBS, Kawasaki disease/MIS-C, and anaphylaxis or anaphylactic shock did not occur during the observation period. Purpura and hemorrhagic conditions were more frequent in the unvaccinated group (7/860 vs. 1/1446), while myocarditis/pericarditis was observed only in the vaccinated group (0/860 vs. 1/1446). Adjusted odds ratio for any of the two adverse events was lower in vaccinated adolescents than in the unvaccinated group which did not reach statistical significance (adjusted odds ratio = 0.14, 95% confidence interval: 0.02, 1.16, P = 0.068). CONCLUSIONS: In this national cohort study of adolescents with CKD in South Korea, we observed no evidence of increased risk of adverse events following BNT162b2 vaccination. Our finding offers insights into the safety of COVID-19 vaccines, empowering adolescent patients with CKD and their caregivers to make informed decisions.

Multi spectral holographic ellipsometry for a complex 3D nanostructure.

We present an innovative ellipsometry technique called self-interferometric pupil ellipsometry (SIPE), which integrates self-interference and pupil microscopy techniques to provide the high metrology sensitivity required for metrology applications of advanced semiconductor devices. Due to its unique configuration, rich angle-resolved ellipsometric information from a single-shot hologram can be extracted, where the full spectral information corresponding to incident angles from 0° to 70° with azimuthal angles from 0° to 360° is obtained, simultaneously. The performance and capability of the SIPE system were fully validated for various samples including thin-film layers, complicated 3D structures, and on-cell overlay samples on the actual semiconductor wafers. The results show that the proposed SIPE system can achieve metrology sensitivity up to 0.123 nm. In addition, it provides small spot metrology capability by minimizing the illumination spot diameter up to 1 µm, while the typical spot diameter of the industry standard ellipsometry is around 30 µm. As a result of collecting a huge amount of angular spectral data, undesirable multiple parameter correlation can be significantly reduced, making SIPE ideally suited for solving several critical metrology challenges we are currently facing.

Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases.

BACKGROUND: Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data. METHODS: Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR. RESULTS: After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59-0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54-0.88 and HR 0.74; CI 0.55-0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62-0.98). CONCLUSIONS: In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Long-term proton pump inhibitor use and risk of osteoporosis and hip fractures: A nationwide population-based and multicenter cohort study using a common data model.

BACKGROUND AND AIM: Association between protonpump inhibitors (PPIs) and osteoporosis, hip fractures has not been fully elucidated. We aimed to evaluate the relationship between PPIs use and the risk of osteoporosis and hip fractures in the databases converted to a common data model (CDM) and to compare the results across the databases. METHODS: This was a population-based, propensity-matched, retrospective cohort study that included patients aged ≥ 50 years who were prescribed with PPIs for over 180 days. We compared the incidence of osteoporosis and hip fractures between new PPI user and new user of other drugs using the Cox proportional hazards model and performed meta-analysis in the electronic health record (EHR) databases. RESULTS: In the Korean National Health Insurance Service (NHIS)-CDM database, long-term PPI users had greater risk of osteoporosis [PPIs vs non-PPIs groups, 28.42/1000 person-years vs 19.29/1000 person-years; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.22-2.15; P = 0.001]. The meta-analytic results of six EHR databases also showed similar result (pooled HR, 1.57; 95% CI, 1.28-1.92). In the analysis of hip fracture, PPI use was not significantly associated with a hip fracture in the NHIS-CDM database (PPI vs non-PPI groups, 3.09/1000 person-years vs 2.26/1000 person-years; HR, 1.45; 95% CI, 0.74-2.80; P = 0.27). However, in the meta-analysis of four EHR databases, the risk of hip fractures was higher in PPI users (pooled HR, 1.82; 95% CI, 1.04-3.19). CONCLUSIONS: Long-term PPI was significantly associated with osteoporosis; however, the results of hip fractures were inconsistent. Further study based on better data quality may be needed.

Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea.

OBJECTIVE: The association between proton pump inhibitor (PPI) use and gastric cancer related to Helicobacter pylori eradication has not been fully investigated in geographical regions with high risk of gastric cancer. We aimed to evaluate the association between PPIs and gastric cancer in Korea. DESIGN: This study analysed the original and common data model versions of the Korean National Health Insurance Service database from 2002 to 2013. We compared the incidence rates of gastric cancer after 1-year drug exposure, between new users of PPIs and other drugs excluding PPIs, by Cox proportional hazards model. We also analysed the incidence of gastric cancer among PPI users after H. pylori eradication. RESULTS: The analysis included 11 741 patients in matched PPI and non-PPI cohorts after large-scale propensity score matching. During a median follow-up of 4.3 years, PPI use was associated with a 2.37-fold increased incidence of gastric cancer (PPI≥30 days vs non-PPI; 118/51 813 person-years vs 40/49 729 person-years; HR 2.37, 95% CI 1.56 to 3.68, p=0.001). The incidence rates of gastric cancer showed an increasing trend parallel to the duration of PPI use. In H. pylori-eradicated subjects, the incidence of gastric cancer was significantly associated with PPI use over 180 days compared with the non-PPI group (PPI≥180 days vs non-PPI; 30/12 470 person-years vs 9/7814 person-years; HR 2.22, 95% CI 1.05 to 4.67, p=0.036). CONCLUSION: PPI use was associated with gastric cancer, regardless of H. pylori eradication status. Long-term PPIs should be used with caution in high-risk regions for gastric cancer.

Physiological and Clinical Assessment of Resting Physiological Indexes.

BACKGROUND: Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indexes according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between resting physiological indexes and the risk of 2-year vessel-oriented composite outcomes (a composite of cardiac death, vessel-related myocardial infarction, and vessel-related ischemia-driven revascularization) was analyzed among 864 deferred vessels. RESULTS: Both RFR and dPR showed a significant correlation with iFR ( R=0.979, P<0.001 for RFR; and R=0.985, P<0.001 for dPR), which was higher than that with fractional flow reserve ( R=0.822, P<0.001; and R=0.819, P<0.001, respectively). RFR and dPR showed a very high agreement with iFR (C index, 0.987 and 0.993). Percent difference of iFR, RFR, and dPR according to the increase in anatomic and hemodynamic severity was almost identical. The diagnostic performance of iFR, RFR, and dPR was not different in the prediction of myocardial ischemia defined by both low hyperemic myocardial blood flow and low coronary flow reserve by 13N-ammonia positron emission tomography. All resting physiological indexes showed significant association with the risk of 2-year vessel-oriented composite outcomes (iFR per 0.1 increase: hazard ratio, 0.514 [95% CI, 0.370-0.715], P<0.001; RFR per 0.1 increase: hazard ratio, 0.524 [95% CI, 0.378-0.725], P<0.001; dPR per 0.1 increase: hazard ratio, 0.587 [95% CI, 0.436-0.791], P<0.001) in deferred vessels. CONCLUSIONS: All resting pressure-derived physiological indexes (iFR, RFR, and dPR) can be used as invasive tools to guide treatment strategy in patients with coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

Comparative risk of Clostridium difficile infection between proton pump inhibitors and histamine-2 receptor antagonists: A 15-year hospital cohort study using a common data model.

BACKGROUNDS AND AIM: There are potential concerns regarding infectious complications including Clostridium difficile infections (CDIs) among patients taking gastric acid suppressants. Furthermore, it is speculated that the stronger acid suppression by proton pump inhibitors (PPIs) potentially enhance infectious complications. This study aimed to compare the risk of CDI between PPIs and histamine-2 receptor antagonists (H2RAs). METHODS: Using the long-term database of the Kangdong Sacred Heart Hospital, converted to the Observational Medical Outcomes Partnership Common Data Model, we identified outpatients treated with PPIs and H2RAs for ≥ 7 days from January 1, 2004 through December 31, 2018. We conducted Cox regression analysis to examine the hazard ratio (HR) of CDI after propensity score matching. RESULTS: During a median follow-up period of 1.2 years (interquartile range, 0.2-3.2 years), the initial CDI occurrence differed significantly between matched cohorts of patients taking PPIs and H2RAs [PPIs vs H2RAs, 88/31 095 person years vs 47/32 836 person years; HR, 2.22; 95% confidence interval (CI) 1.29-3.96; P = 0.005]. Almost 50% of all events occurred within 1 year of drug exposure. The risk of CDIs was significantly greater among groups receiving PPIs or H2RAs than in matched controls (PPIs vs control: HR, 2.65; 95% CI 1.28-5.79; P = 0.011; and H2RAs vs control: HR 2.43; 95% CI 1.09-5.68; P = 0.034]. CONCLUSION: In long-term hospital cohort, outpatient-based PPIs were associated with greater risk of CDI than H2RAs. It is necessary to be cautioned about complication of CDI in patients taking long-term PPI therapy.

Reduced awareness of surroundings is the most central domain in the network structure of posttraumatic stress disorder symptoms.

Backgroud: Network models suggest that co-occurring symptoms are conceptualized as a syndrome due to interactions, rather than a categorical entity with an underlying common cause.Aim: Our study aimed to examine the network structure and centrality of Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV posttraumatic stress disorder (PTSD) symptoms, including essential and associated features.Methods: We constructed a network structure of 21 intertwined symptoms, evaluated with the Clinician-Administered PTSD Scale (CAPS), in 249 PTSD patients who have been exposed to various types of traumatic events (73% being traffic or other accidents) and were beginning psychiatric treatment. In addition, we estimated the centrality of the 21 symptoms through network analysis. Each of the symptoms was defined as ordered-categorical variables.Results: The network, with 21 symptoms, demonstrated a strong correlation among difficulty concentrating, reduced awareness of surroundings, and derealization. In addition, reduced awareness of surroundings was estimated as the most central symptom, whereas inability to recall important aspects of trauma was estimated as the least central symptom in the subjects. A community-detection analysis estimated that the 21 PTSD symptoms were organized into three clinically meaning clusters.Conclusion: Although dissociative features have been defined as associative symptoms rather than essential symptoms for the DSM diagnostic criteria, reduced awareness of surroundings may be regarded as the most central symptom in patients in the early phase of PTSD. Thus, evaluation and intervention for dissociative features may be needed in clinical practice and studies on PTSD.

Spectrum of susceptibility to air quality and weather in individual children with atopic dermatitis.

BACKGROUND: Exposure to air pollution aggravates symptoms of atopic dermatitis (AD) in children in the population studies. Variability in individual patient's response from individual susceptibility is needed to be explored. OBJECTIVE: This study aimed to investigate spectrum of individual variability in the associations between AD symptoms and air quality. METHODS: We enrolled 89 children aged 0-6 years with AD (22 890 person-days). Daily manifestation of symptoms was recorded for an average of 257 days (range 100-499). Both an individual analysis using logistic regression models and an overall analysis using a generalized estimating equation were performed. RESULTS: The odds ratios of an individual ranged 0.24-8.11 for particulate matter <10 µm in diameter (PM10 ), 0.09-101.92 for nitrogen oxide (NO2 ), 0.03-44.00 for ozone (O3 ), 0.11-58.30 for sulfur dioxide (SO2 ), 0.00-15.83 for carbon monoxide (CO), 0.00-39 446.94 for temperature, and 0.03-5.18 for relative humidity, demonstrating a wide individual variability. In the overall analysis, PM10 , NO2 , SO2 , and CO had a significantly positive association, whereas temperature and relative humidity were negatively associated with AD symptoms. Air pollution was responsible for aggravation of symptoms from 24.7% (O3 ) to 39.3% (SO2 ) of AD children. Overall, 71.9% of the AD children responded to at least one or more air pollution and weather variable. CONCLUSION: Responses of AD children to air pollution and weather variable were considerably variable among individuals. An individualized model would be useful to forecast and manage AD symptoms in patients.

Clinical Outcome of Lesions With Discordant Results Among Different Invasive Physiologic Indices　- Resting Distal Coronary to Aortic Pressure Ratio, Resting Full-Cycle Ratio, Diastolic Pressure Ratio, Instantaneous Wave-Free Ratio, and Fractional Flow Reserve.

BACKGROUND: We evaluated the 2-year clinical outcomes of deferred lesions with discordant results between resting and hyperemic pressure-derived physiologic indices, including resting distal to aortic coronary pressure (resting Pd/Pa), instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and fractional flow reserve (FFR).Methods and Results:The 2-year clinical outcomes of 1,024 vessels (435 patients) with available resting Pd/Pa, iFR, RFR, dPR, and FFR data were analyzed according to a 4-group classification using known cutoff values (resting Pd/Pa ≤0.92, iFR/RFR/dPR ≤0.89, and FFR ≤0.80): Group 1 (concordant normal), Group 2 (high resting index and low FFR), Group 3 (low resting index and high FFR), and Group 4 (concordance abnormal). The primary outcome was vessel-oriented composite outcomes (VOCO) in deferred vessels at 2 years. In the comparison of VOCO risk among 4 groups classified according to FFR and 4 resting physiologic indices, Group 4 consistently showed a significantly higher risk of VOCO than Group 1. Comparison of VOCO risk among 4 groups classified according to iFR and other resting physiologic indices also showed the same results. The presence of discordance, either between hyperemic and resting indices or among resting indices, was not an independent predictor for VOCO. CONCLUSIONS: Discordant results between resting physiologic indices and FFR and among the resting indices were not associated with increased risk of VOCO in deferred lesions.

Intermittent burst of a super rogue wave in the breathing multi-soliton regime of an anomalous fiber ring cavity.

We report the intermittent burst of a super rogue wave in the multi-soliton (MS) regime of an anomalous-dispersion fiber ring cavity. We exploit the spatio-temporal measurement technique to log and capture the shot-to-shot wave dynamics of various pulse events in the cavity, and obtain the corresponding intensity probability density function, which eventually unveils the inherent nature of the extreme events encompassed therein. In the breathing MS regime, a specific MS regime with heavy soliton population, the natural probability of pulse interaction among solitons and dispersive waves exponentially increases owing to the extraordinarily high soliton population density. Combination of the probabilistically started soliton interactions and subsequently accompanying dispersive waves in their vicinity triggers an avalanche of extreme events with even higher intensities, culminating to a burst of a super rogue wave nearly ten times stronger than the average solitons observed in the cavity. Without any cavity modification or control, the process naturally and intermittently recurs within a time scale in the order of ten seconds.

Metallic Fresnel zone plate implemented on an optical fiber facet for super-variable focusing of light.

We propose and investigate a metallic Fresnel zone plate (FZP/MFZP) implemented on a silver-coated optical fiber facet for super-variable focusing of light, the focal point of which can be drastically relocated by varying the wavelength of the incident light. We numerically show that when its nominal focal length is set to 20 µm at 550 nm, its effective focal length can be tuned by ~13.7 µm for 300-nm change in the visible wavelength range. This tuning sensitivity is over 20 times higher than that of a conventional silica-based spherical lens. Even with such high tuning sensitivity with respect to the incident wavelength change, the effective beam radius at the focal point is preserved nearly unchanged, irrespective of the incident wavelength. Then, we fabricate the proposed device, exploiting electron- and focused-ion-beam processes, and experimentally verify its super-variable focusing functionality at typical red, green, and blue wavelengths in the visible wavelength range, which is in good agreement with the numerical prediction. Moreover, we propose a novel MFZP structure that primarily exploits the surface-plasmon-polariton-mediated, extra-ordinary transmission effect. For this we make all the openings of an MFZP, which are determined by the fundamental FZP design formula, be partitioned by multi-rings of all-sub-wavelength annular slits, so that the transmission of azimuthally polarized light is inherently prohibited, thereby leading to super-variable and selective focusing of radially polarized light. We design and fabricate a proof-of-principle structure implemented on a gold-coated fused-silica substrate, and verify its novel characteristics both numerically and experimentally, which are mutually in good agreement. We stress that both the MFZP structures proposed here will be very useful for micro-machining, optical trapping, and biomedical sensing, in particular, which invariably seek compact, high-precision, and flexible focusing schemes.

Corrugation-assisted metal-coated angled fiber facet for wavelength-dependent off-axis directional beaming.

We propose a fiber-optic-plasmonic hybrid device that is based on a corrugation-assisted metal-coated angled fiber facet (CA-MCAFF) for wavelength-dependent off-axis directional beaming (WODB). The device breaks into two key structures: One is the MCAFF structure, which is a modified Kretschmann configuration implemented onto a fiber platform, thereby being able to generate a unidirectional surface plasmon with dramatically enhanced properties in terms of non-confined diffracted radiation loss and operational bandwidth. The other is the periodic corrugation structure put on the MCAFF, thereby enabling WODB functionality out of the whole structures. The corrugated metal surface out-couples the surface plasmon mode to free-space optical radiation into a direction that varies with the wavelength of the optical radiation with excellent linearity. We perform extensive numerical investigations based on the finite-element-method and analyze the out-coupling efficiency (OCEout) and spectral bandwidth (SBout) of the proposed device for various designs and conditions. We determine the seven structural parameters of the device via taking sequential optimization steps. We deduce two optimal conditions particularly for the fiber-facet angle, in terms of the averaged OCEout or the SBout in the whole visible wavelength range (400 - 700 nm), which eventually leads to OCEout = 30.4% and SBout = 230 nm or to OCEout = 24.5% and SBout = 245 nm, respectively. These results suggest substantial enhancements in both OCEout and SBout, in comparison with the performance properties of a typical nano-slit-based device having a similar type of WODB functionality. The proposed CA-MCAFF is a simple, compact and efficient WODB device that is fully compatible with the state-of-the-art optical fiber technology.

Theoretical study on the generation of a low-noise plasmonic hotspot by means of a trench-assisted circular nano-slit.

We propose a novel trench-assisted circular metal nano-slit (CMNS) structure implementable on a fiber platform for the generation of a low-noise cylindrical surface plasmon (CSP) hotspot. We design trench structures based on a multi-pole cancellation method in order that a converging surface plasmon signal is well separated from co-propagating non-confined diffracted light (NCDL) at the hotspot location. In fact, the secondary radiation by the quasi-pole oscillation at the edge of the trench cancels the primary NCDL, thereby enhancing the signal-to-noise ratio (SNR) of the CSP hotspot. In particular, we investigate two types of trench structures: a rectangular-trench (RT) structure and an asymmetric-parabolic-trench (APT) structure, which are considered for the sake of the simplicity of fabrication and of the maximal enhancement of the SNR, respectively. In comparison with a conventional CMNS having no trenches, we highlight that the mean SNR of the CSP hotspot is enhanced by 6.97 and 11.89 dB in case of the optimized RT and APT CMNSs, respectively. The proposed schemes are expected to be useful for increasing the SNR of plasmonic devices that are interfered by NCDL, such as various types of nano-slits for generating high-resolution plasmonic signals, for example.

Optimization of electrochemical regeneration of intercalated MXene for the adsorptive removal of ciprofloxacin: Prospective mechanism.

2D-Ti3C2Tx MXene nanosheets intercalated with sodium ions (SI-Ti3C2Tx) were synthesized and utilized in simultaneous adsorption and electrochemical regeneration with ciprofloxacin (CPX). The primary focus of this study is to investigate the long-term stability of SI-Ti3C2Tx MXene and to propose the underlying regeneration mechanisms. The successful synthesis of Ti3AlC2, Ti3C2Tx MXene, and SI-Ti3C2Tx MXene was confirmed using X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy. Electrochemical regeneration parameters such as charge passed, regeneration time, current density, and electrolyte composition were optimized with values of 787.5 C g-1, 7.5 min, 10 mA cm-2, and 2.5w/v% sodium chloride, respectively, enabling the complete regeneration of the SI-Ti3C2Tx MXene. In addition, the electrochemical regeneration significantly enhanced CPX removal from the SI-Ti3C2Tx MXene owing to partial amorphization, disorderliness, increased functional groups, delamination, and defect creation in the structure. Thus, the synthesized nano-adsorbent has proven helpful in practical water treatment with optimized electrochemical regeneration processes.

Timely Pulmonary Tuberculosis Diagnosis Based on the Epidemiological Disease Spectrum: Population-Based Prospective Cohort Study in the Republic of Korea.

BACKGROUND: Timely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. OBJECTIVE: We aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. METHODS: The Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. RESULTS: Among the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. CONCLUSIONS: Timely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption.

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study.

AIMS: Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers. METHODS AND RESULTS: Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group. CONCLUSION: Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers.

In this study of 19 425 participants, we investigated whether alcohol consumption reduction was associated with lower risk of incident atrial fibrillation (AF) in individuals with chronic heavy alcohol consumption. The absolute abstinence significantly reduced incident AF, but reducing alcohol consumption was not associated with a lower incident AF. The benefit of absolute abstinence for incidence of AF was significantly identified in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease.

Risks of long-term use of proton pump inhibitor on ischemic vascular events: A distributed network analysis of 5 real-world observational Korean databases using a common data model.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed drugs. However, it has been suggested that they are associated with an increased risk of ischemic vascular events (IVE) including stroke, although the data are inconsistent. AIMS: We investigated the association between PPIs use and IVE in five observational Korean databases using a common data model (CDM). METHODS: This study included patient-based retrospective, observational cohort data of subjects aged over 18 years between January 1, 2004, and December 31, 2020, from five medical centers as part of the Observational Medical Outcomes Partnership (OMOP) CDM. Subjects who were included in both cohorts or had a previous history of ischemic stroke were excluded. After propensity matching, 8007 propensity-matched pairs between the PPIs and H2 receptor antagonist (H2RA) users were included in this study. RESULTS: In the 1:1 propensity score matching with 8007 in each group, long-term PPIs use (⩾365 days) was not associated with ischemic stroke (odds ratio (OR) = 1.05, 95% confidence interval (CI) 0.71-1.56; I2 = 57%), ischemic stroke and transient ischemic attack (OR = 1.02, 95% CI 0.71-1.48; I2 = 53%), and net adverse clinical events (OR = 1.08, 95% CI 0.83-1.40; I2 = 47%) compared with H2RAs users. CONCLUSIONS: Our analysis in a large dataset found no evidence that long-term use of PPIs was associated with an increased risk of ischemic stroke.

Association between cardio-cerebrovascular disease and systemic antipsoriatic therapy in psoriasis patients using population-based data: A nested case-control study.

The effect of antipsoriatic therapy on cardio-cerebrovascular disease (CCVD) is not well described. Thus, we performed a population-based nested case-control study to investigate the effect of systemic antipsoriatic therapy on CCVD in psoriasis patients. Using nationwide cohort data from the Korean National Health Insurance Claims database, newly diagnosed psoriasis patients were identified. Among the enrolled participants, postenrollment development of CCVD events (ischemic heart disease, myocardial infarction, cerebral infarction, and cerebral hemorrhage) was investigated. To evaluate the effect of systemic antipsoriatic therapy on CCVD risk, we calculated the proportion of the treatment period with systemic antipsoriatic therapy during the study period (PTP [%]: the sum of all systemic antipsoriatic therapy durations divided by total observation period). Among 251 813 participants, 6262 experienced CCVD events during the study period (CCVD group). Controls included 245 551 patients without CCVD history during the study period (non-CCVD group). The non-CCVD group had greater PTP than the CCVD group (CCVD 2.12 ± 7.92, non-CCVD 2.64 ± 9.64; P < 0.001). In multiple logistic regression analysis, PTP was inversely associated with the CCVD risk after adjusting for age, sex, diabetes, hypertension, and dyslipidemia. A 10% increase in PTP reduced CCVD risk by 0.96 (95% confidence interval 0.93 to 0.99). Reduced CCVD risk was robust for both conventional antipsoriatic therapy and biologics. Our study found that systemic antipsoriatic therapy use was inversely associated with CCVD risk in psoriasis patients. These findings suggested that systemic antipsoriatic therapy could reduce CCVD development in patients with psoriasis.