Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension.

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

Effects on viral suppression and the early-immune expression of ribavirin against spring viremia of carp virus in vitro.

Spring viremia of carp virus (SVCV) is a globally distributed virus that causes severe clinical symptoms and high mortality in fish belonging to the families Cyprinidae and Siluridae. To protect the host against viral infection, understanding the relatedness between viral susceptibility and antiviral mechanisms must be crucial. Thus, we evaluated the viral suppression efficacy of ribavirin by measuring the transcription levels of viral and immune genes in vitro. The results showed that following ribavirin treatment after SVCV infection (MOI 0.1), ribavirin inhibited SVCV replication in epithelioma papulosum cyprini (EPC) cells and completely inhibited viral gene (G and N) expression at concentrations above 10 µg/mL at 48 h post-infection. Ribavirin does not directly damage SVCV particles but inhibits early viral replication. In the absence of SVCV infection, the immunological dynamics triggered by ribavirin resulted in upregulated pattern recognition receptors and proinflammatory cytokine-related genes (i.e., PI3K, MYD88, IRAK1, RIG-І, MAVS, Mx1, TNF-α, and NF-κB). Furthermore, EPC cells treated with ribavirin following SVCV infection showed upregulation of PI3K, MYD88, IRAK1, RIG-І, TNF-α, and NF-κB genes within 24 h post-SVCV infection, suggesting that ribavirin positively inhibits the SVCV infection in vitro.

The role of ambulatory blood pressure monitoring in enhancing medication adherence among patients with newly diagnosed hypertension: an analysis of the National Health Insurance cohort database.

BACKGROUND: Improving adherence to antihypertensive medication (AHM) is a key challenge in hypertension management. This study aimed to assess the impact of ambulatory blood pressure monitoring (ABPM) on AHM adherence. METHODS: We utilized the Korean National Health Insurance Service database. Among patients newly diagnosed with hypertension who started AHM between July 2010 and December 2013, we compared clinical characteristics and adherence between 28,116 patients who underwent ABPM prior to starting AHM and 118,594 patients who did not undergo ABPM. Good adherence was defined as a proportion of days covered (PDC) of 0.8 or higher. RESULTS: The total study population was 146,710, with a mean age of 50.5 ± 6.4 years; 44.3% were female. Co-morbidities were noted in 4.2%. About a third of patients (33.1%) showed good adherence. The ABPM group had a notably higher PDC (total PDC: 0.64 ± 0.35 vs. 0.45 ± 0.39; P < 0.001), irrespective of the number of medications, dosing frequency, or prescription duration. After adjusting for significant clinical variables, ABPM was still closely linked with good adherence (odds ratio, 2.35; 95% confidence interval, 2.28-2.41; P < 0.001). CONCLUSIONS: In newly diagnosed hypertension, undergoing ABPM prior to AHM prescription appears to enhance adherence to AHM. The exact mechanisms driving this association warrant further exploration.

Digital Health Technology Use Among Older Adults: Exploring the Impact of Frailty on Utilization, Purpose, and Satisfaction in Korea.

BACKGROUND: The importance of digital technology is increasing among older adults. In this study, the digital health technology utilization status, purpose, and satisfaction of older adults were investigated according to frailty. METHODS: A face-to-face survey was conducted among adults aged 65 years or older. Frailty was defined using the Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight scale. RESULTS: A total of 505 participants completed the survey, with 153 (30.3%) identified as pre-frail or frail and 352 (69.7%) as healthy. All respondents used smartphones; 440 (87.1%) were application users, and 290 (57.4%) were healthcare application users. Wearable devices were used by only 36 patients (7.1%). Pre-frail or frail respondents used social media more frequently than healthy respondents (19.4% vs. 7.4%, P < 0.001). Among the respondents, 319 (63.2%) were not able to install or delete the application themselves, and 277 (54.9%) stated that the application was recommended by their children (or partner). Pre-frail and frail respondents used more healthcare applications to obtain health information (P = 0.002) and were less satisfied with wearable devices (P = 0.02). CONCLUSION: The usage rate of digital devices, including mobile phones among older adults in Korea is high, whereas that of wearable devices is low. There was a notable difference in the services used by pre-frail and frail respondents compared to healthy respondents. Therefore, when developing digital devices for pre-frail and frail older adults, it is crucial to incorporate customized services that meet their unique needs, particularly those services that they frequently use.

Development of a claims-based risk-scoring model to predict emergency department visits in older patients receiving anti-neoplastic therapy.

This study developed and validated a risk-scoring model, with a particular emphasis on medication-related factors, to predict emergency department (ED) visits among older Korean adults (aged 65 and older) undergoing anti-neoplastic therapy. Utilizing national claims data, we constructed two cohorts: the development cohort (2016-2018) with 34,642 patients and validation cohort (2019) with 10,902 patients. The model included a comprehensive set of predictors: demographics, cancer type, comorbid conditions, ED visit history, and medication use variables. We employed the least absolute shrinkage and selection operator (LASSO) regression to refine and select the most relevant predictors. Out of 120 predictor variables, 12 were integral to the final model, including seven related to medication use. The model demonstrated acceptable predictive performance in the validation cohort with a C-statistic of 0.76 (95% CI 0.74-0.77), indicating reasonable calibration. This risk-scoring model, after further clinical validation, has the potential to assist healthcare providers in the effective management and care of older patients receiving anti-neoplastic therapy.

Protective Effects of Bombyx batryticatus Protein-Rich Extract Against Cisplatin-Induced Nephrotoxicity in HEK293 Cells and a Mouse Model.

Cisplatin, a potent and prominent chemotherapeutic drug, has considerable side effects, including nephrotoxicity, which limits its therapeutic application and efficacy. Therefore, the development of agents that protect normal cells while preserving cisplatin's chemotherapeutic properties is of utmost importance. This study aimed to explore the protective effects of Bombyx batryticatus protein-rich extract (BBPE) against cisplatin-induced nephrotoxicity in a cisplatin-treated mouse model and human embryonic kidney (HEK293) cells. Apoptosis was assessed in HEK293 cells to determine the cytoprotective effects of BBPE and its effects on the generation of cisplatin-induced reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) collapse. Although cisplatin induced nephrotoxicity in HEK293 cells, pretreatment with BBPE showed significant protective effects against cisplatin-induced nephrotoxicity by regulating the expression levels of pro- and antiapoptotic proteins. The cytoprotective effects of BBPE were mediated by decreased ROS production and MTP loss in cisplatin-treated HEK293 cells. The in vitro results were confirmed in the cisplatin-treated mouse model. Pretreatment with BBPE protected against cisplatin-induced nephrotoxicity by restoring malondialdehyde, superoxide dismutase, and catalase levels in kidney tissue and blood urea nitrogen and creatinine serum levels. Furthermore, histopathological assessment and terminal dUTP nick end-labeling staining showed that BBPE mitigated cisplatin-induced nephrotoxicity in kidney tissues. Overall, BBPE may act as a potent agent for alleviating cisplatin-induced nephrotoxicity, thereby increasing the safety of cisplatin-based chemotherapy.

Development and validation of a machine learning-based fall-related injury risk prediction model using nationwide claims database in Korean community-dwelling older population.

BACKGROUND: Falls impact over 25% of older adults annually, making fall prevention a critical public health focus. We aimed to develop and validate a machine learning-based prediction model for serious fall-related injuries (FRIs) among community-dwelling older adults, incorporating various medication factors. METHODS: Utilizing annual national patient sample data, we segmented outpatient older adults without FRIs in the preceding three months into development and validation cohorts based on data from 2018 and 2019, respectively. The outcome of interest was serious FRIs, which we defined operationally as incidents necessitating an emergency department visit or hospital admission, identified by the diagnostic codes of injuries that are likely associated with falls. We developed four machine-learning models (light gradient boosting machine, Catboost, eXtreme Gradient Boosting, and Random forest), along with a logistic regression model as a reference. RESULTS: In both cohorts, FRIs leading to hospitalization/emergency department visits occurred in approximately 2% of patients. After selecting features from initial set of 187, we retained 26, with 15 of them being medication-related. Catboost emerged as the top model, with area under the receiver operating characteristic of 0.700, along with sensitivity and specificity rates around 65%. The high-risk group showed more than threefold greater risk of FRIs than the low-risk group, and model interpretations aligned with clinical intuition. CONCLUSION: We developed and validated an explainable machine-learning model for predicting serious FRIs in community-dwelling older adults. With prospective validation, this model could facilitate targeted fall prevention strategies in primary care or community-pharmacy settings.

Resistant hypertension: consensus document from the Korean society of hypertension.

Although reports vary, the prevalence of true resistant hypertension and apparent treatment-resistant hypertension (aTRH) has been reported to be 10.3% and 14.7%, respectively. As there is a rapid increase in the prevalence of obesity, chronic kidney disease, and diabetes mellitus, factors that are associated with resistant hypertension, the prevalence of resistant hypertension is expected to rise as well. Frequently, patients with aTRH have pseudoresistant hypertension [aTRH due to white-coat uncontrolled hypertension (WUCH), drug underdosing, poor adherence, and inaccurate office blood pressure (BP) measurements]. As the prevalence of WUCH is high among patients with aTRH, the use of out-of-office BP measurements, both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM), is essential to exclude WUCH. Non-adherence is especially problematic, and methods to assess adherence remain limited and often not clinically feasible. Therefore, the use of HBPM and higher utilization of single-pill fixed-dose combination treatments should be emphasized to improve drug adherence. In addition, primary aldosteronism and symptomatic obstructive sleep apnea are quite common in patients with hypertension and more so in patients with resistant hypertension. Screening for these diseases is essential, as the treatment of these secondary causes may help control BP in patients who are otherwise difficult to treat. Finally, a proper drug regimen combined with lifestyle modifications is essential to control BP in these patients.

The role of radiolabeling in BNCT tracers for enhanced dosimetry and treatment planning.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are potent technologies for non-invasive imaging of pharmacological and biochemical processes in both preclinical and advanced clinical research settings. In the field of radiation therapy, boron neutron capture therapy (BNCT) stands out because it harnesses biological mechanisms to precisely target tumor cells while preserving the neighboring healthy tissues. To achieve the most favorable therapeutic outcomes, the delivery of boron-enriched tracers to tumors must be selective and efficient, with a substantial concentration of boron atoms meticulously arranged in and around the tumor cells. Although several BNCT tracers have been developed to facilitate the targeted and efficient delivery of boron to tumors, only a few have been labeled with PET or SPECT radionuclides. Such radiolabeling enables comprehensive in vivo examination, encompassing crucial aspects such as pharmacodynamics, pharmacokinetics, tumor selectivity, and accumulation and retention of the tracer within the tumor. This review provides a comprehensive summary of the essential aspects of BNCT tracers, focusing on their radiolabeling with PET or SPECT radioisotopes. This leads to more effective and targeted treatment approaches which ultimately enhance the quality of patient care with respect to cancer treatment.

Effect of multimorbidity on hypertension management.

Multimorbidity, the coexistence of multiple health conditions, is associated with functional decline, disability, and mortality. We aimed to investigate the effects of multimorbidity on hypertension treatment and control rates by analyzing data from the Korean National Health and Nutrition Examination Survey database, which is a cross-sectional, nationally representative survey conducted by the Korean government. Multimorbidity, defined as having two or more chronic diseases, was evaluated by blood pressure measurements, blood chemistry examinations, and questionnaires. We classified the participants according to the number of multimorbidities from 0 to ≥ 6. Association analysis was performed to identify the patterns of multimorbidity related to hypertension control. From 2016 to 2020, 30,271 adults (≥ 20 years) were included in the analysis (age: 52.1 ± 16.8 years, male: 44.0%), and 14,278 (47.2%) had multimorbidity. The number of chronic conditions was significantly higher in older adults, women, and hypertensive patients. Multimorbidity was associated with hypertension treatment. The number of chronic conditions was significantly higher in controlled compared to uncontrolled patients (3.6 ± 1.7 vs 2.9 ± 1.6, p < 0.001). But the control rate of hypertension among treated patients was lower in patients with multimorbidity (75.6% in hypertension only group vs 71.8% in multimorbidity group, p = 0.009). Multimorbidity patterns showed distinct features in treated and controlled hypertensive patients. In conclusion, multimorbidity has a beneficial effect on the treatment of hypertension, but the control rate of systolic blood pressure was lower among the patients with multimorbidity. More attention should be paid to the hypertensive patients with multimorbidity to improve the control rate of hypertension.

Identification of Various InDel-II Variants of the White Spot Syndrome Virus Isolated from Frozen Shrimp and Bivalves Obtained in the Korean Commercial Market.

White spot syndrome virus (WSSV) poses a significant threat to the global shrimp industry. We investigated the presence of WSSV in frozen shrimp (n = 86) and shellfish (n = 185) from the Korean market (2010-2018). The detection rate of first-step polymerase chain reaction (PCR) in domestic shrimp was 36.8% (7/19), whereas that in imported shrimp was 0.01% (1/67). Furthermore, the WSSV genome was amplified from domestic bivalve mollusks by first- and second-step PCR with accuracies of 3.4% (5/147) and 15.6% (23/147), respectively. The genetic relatedness of InDel-II regions among WSSVs detected in domestic shrimp groups revealed four variants (777, 5649, 11,070 and 13,046 bp insertion or deletion), and imported shrimp groups had four variants (10,778, 11,086, 11,500 and 13,210 bp) compared with the putative ancestor WSSV strain. The 5649 bp variant was the dominant type among the WSSV variants detected in domestic shrimp (54.5%, 6/11). Notably, bivalve mollusks exhibited six variants (777, 5649, 5783, 5876, 11,070 and 13,046 bp), including four variants detected in shrimp, indicating that bivalve mollusks could facilitate WSSV tracking. In a challenge test, whiteleg shrimp (Litopenaeus vannamei) exhibited varying mortality rates, indicating a link between InDel-II deletion and viral replication. These findings highlight the complexity of WSSV transmission.

Development and Validation of a Prognostic Classification Model Predicting Postoperative Adverse Outcomes in Older Surgical Patients Using a Machine Learning Algorithm: Retrospective Observational Network Study.

BACKGROUND: Older adults are at an increased risk of postoperative morbidity. Numerous risk stratification tools exist, but effort and manpower are required. OBJECTIVE: This study aimed to develop a predictive model of postoperative adverse outcomes in older patients following general surgery with an open-source, patient-level prediction from the Observational Health Data Sciences and Informatics for internal and external validation. METHODS: We used the Observational Medical Outcomes Partnership common data model and machine learning algorithms. The primary outcome was a composite of 90-day postoperative all-cause mortality and emergency department visits. Secondary outcomes were postoperative delirium, prolonged postoperative stay (≥75th percentile), and prolonged hospital stay (≥21 days). An 80% versus 20% split of the data from the Seoul National University Bundang Hospital (SNUBH) and Seoul National University Hospital (SNUH) common data model was used for model training and testing versus external validation. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) with a 95% CI. RESULTS: Data from 27,197 (SNUBH) and 32,857 (SNUH) patients were analyzed. Compared to the random forest, Adaboost, and decision tree models, the least absolute shrinkage and selection operator logistic regression model showed good internal discriminative accuracy (internal AUC 0.723, 95% CI 0.701-0.744) and transportability (external AUC 0.703, 95% CI 0.692-0.714) for the primary outcome. The model also possessed good internal and external AUCs for postoperative delirium (internal AUC 0.754, 95% CI 0.713-0.794; external AUC 0.750, 95% CI 0.727-0.772), prolonged postoperative stay (internal AUC 0.813, 95% CI 0.800-0.825; external AUC 0.747, 95% CI 0.741-0.753), and prolonged hospital stay (internal AUC 0.770, 95% CI 0.749-0.792; external AUC 0.707, 95% CI 0.696-0.718). Compared with age or the Charlson comorbidity index, the model showed better prediction performance. CONCLUSIONS: The derived model shall assist clinicians and patients in understanding the individualized risks and benefits of surgery.

Standardized protocol of blood pressure measurement and quality control program for the Korea National Health and Nutrition Examination Survey.

Accurate blood pressure (BP) measurement is crucial for hypertension detection and management. The Korea National Health and Nutrition Examination Survey (KNHANES) assesses the health of Koreans using representative cross-sectional data. BP measurements were historically done with mercury sphygmomanometers for participants aged ≥10 years. However, KNHANES transitioned to Greenlight 300TM (mercury-free auscultatory device) in 2020 for participants aged ≥6 years and used dual devices (Microlife WatchBP Office AFIB and Greenlight) in 2021-2022. To ensure consistency, KNHANES will adopt Microlife as the unified BP device with Greenlight for device validation from 2023. Under the new protocol, participants aged ≥6 years will have their BP measured three times at 30-second intervals after a 5-minute rest under ambient temperature (20-25℃) and noise ≤65 dB. The average of the 2nd and 3rd readings will be used as the representative BP value. The quality control (QC) program involves four trained examiners passing the "quality control and assurance of BP measurement program" three times annually, and undergoing "video monitoring of weekly calibration process" once a year. Additionally, the QC team will conduct "on-site evaluations of BP measurement" at mobile examination centers three times a year. A Five-Step QC process for BP devices was also developed. This document outlines the standardized BP measurement protocol and rigorous QC program in KNHANES, aiming to ensure accurate and reliable BP data for epidemiological research and public health policymaking in South Korea.

Diagnostic validity of molecular diagnostic assays for white spot syndrome virus at different severity grades.

The high virulence of the white spot syndrome virus (WSSV) in acute infections and the lack of effective treatments underscore the necessity for a rapid, accurate, and efficient diagnostic process to control white spot disease. The analytical sensitivity of diagnostic assays (polymerase chain reactions; PCRs and rapid diagnostic kit) at different severity grades of WSSV infection were determined using the 95% limit of detection (LOD95%). The LOD95% of nested, real-time, and one-step PCRs and rapid diagnostic kit were 0.70, 4.67, 1.19, and 79,434.65 viral genome copies/reactions, respectively. From the intramuscular challenge tests conducted under different dose and temperature conditions, the WSSV severity grades of time-course collected whiteleg shrimp (Litopenaeus vannamei) and dead or live shrimps were determined based on the viral loads of the pleopod. By applying the WSSV severity grades, a total of 92 shrimps were classified as G0. Furthermore, 92, 66, 199, and 79 shrimps were classified as G1, G2, G3, and G4, respectively. Additionally, 222 shrimps were classified as negative as WSSV was not confirmed in the nested PCR assay. Diagnostic sensitivity (DSe) and specificity (DSp) values of molecular diagnostic assays were compared with those of nested PCR in artificial WSSV-infected shrimp to evaluate diagnostic performance. The real-time and one-step PCRs exhibited a DSe >92.4% for G0 grade (approximately 101-102 copies/mg), indicating WSSV detection at low copy numbers. The rapid diagnostic kit presented a DSe >92.4% for G2 grade (approximately 104-105 copies/mg), suggesting the detection of WSSV-infected shrimp with clinical signs during the endemic period. These results suggest that the strategy of presumptive diagnosis using one-step PCR and rapid diagnostic kit at different seasonal periods followed by confirmatory diagnosis using real-time PCR assay could aid in controlling WSD with rapidity, accuracy, and cost-effectiveness.

Statement on chronotherapy for the treatment of hypertension: consensus document from the Korean society of hypertension.

Nocturnal blood pressure (BP) has been shown to have a significant predictive value for cardiovascular disease. In some cases, it has a superior predictive value for future cardiovascular outcomes than daytime BP. As efficacy of BP medications wanes during nighttime and early morning, control of nocturnal hypertension and morning hypertension can be difficult. As such, chronotherapy, the dosing of BP medication in the evening, has been an ongoing topic of interest in the field of hypertension. Some studies have shown that chronotherapy is effective in reducing nocturnal BP, improving non dipping and rising patterns to dipping patterns, and improving cardiovascular prognosis. However, criticism and concerns have been raised regarding the design of these studies, such as the Hygia study, and the implausible clinical benefits in cardiovascular outcomes considering the degree of BP lowering from bedtime dosing. Studies have shown that there is no consistent evidence to suggest that routine administration of antihypertensive medications at bedtime can improve nocturnal BP and early morning BP control. However, in some cases of uncontrolled nocturnal hypertension and morning hypertension, such as in those with diabetes mellitus, chronic kidney disease, and obstructive sleep apnea, bedtime dosing has shown efficacy in reducing evening and early morning BP. The recently published the Treatment in Morning versus Evening (TIME) study failed to demonstrate benefit of bedtime dosing in reducing cardiovascular outcomes in patients with hypertension. With issues of the Hygia study and negative results from the TIME study, it is unclear at this time whether routine bedtime dosing is beneficial for reducing cardiovascular outcomes.

Association between office visit intervals and long-term cardiovascular risk in hypertensive patients.

Hypertension is a chronic disease that requires long-term follow-up in many patients, however, optimal visit intervals are not well-established. This study aimed to evaluate the incidences of major cardiovascular events (MACEs) according to visit intervals. We analyzed data from 9894 hypertensive patients in the Korean Hypertension Cohort, which enrolled and followed up 11,043 patients for over 10 years. Participants were classified into five groups based on their median visit intervals (MVIs) during the 4-year period and MACEs were compared among the groups. The patients were divided into clinically relevant MVIs of one (1013; 10%), two (1299; 13%), three (2732; 28%), four (2355; 24%), and six months (2515; 25%). The median follow-up period was 5 years (range: 1745 ± 293 days). The longer visit interval groups did not have an increased cumulative incidence of MACE (12.9%, 11.8%, 6.7%, 5.9%, and 4%, respectively). In the Cox proportional hazards model, those in the longer MVI group had a smaller hazard ratio (HR) for MACEs or all-cause death: 1.77 (95% confidence interval [CI], 1.45-2.17), 1.7 (95% CI: 1.41-2.05), 0.90 (95% CI: 0.74-1.09) and 0.64 (95% CI: 0.52-0.79), respectively (Reference MVI group of 75-104 days). In conclusion, a follow-up visits with a longer interval of 3-6 months was not associated with an increased risk of MACE or all-cause death in hypertensive patients. Therefore, once medication adjustment is stabilized, a longer interval of 3-6 months is reasonable, reducing medical expenses without increasing the risk of cardiovascular outcomes.

Risk Stratification of Cardiovascular Disease according to Age Groups in New Prevention Guidelines: A Review.

Age is a strong risk factor for cardiovascular disease. Accordingly, most cardiovascular risk prediction models have included age as an independent risk factor. There is much evidence that effective management of cardiovascular risk factors improves clinical outcomes even in older adults. However, there are concerns that intensive treatment for older adults increases the risk of adverse events. For hypertensive patients, intensive blood pressure reduction with combination therapy increases the risk of syncope, acute kidney injury, and falls. Intensive glucose-lowering therapy among older patients with diabetes increases the risk of hypoglycemia or cognitive impairment. These findings suggest that a balanced approach for older adults is required to increase the benefits and decrease the risk of side effects. In contrast to older people, the estimated 10-year cardiovascular risk in young and healthy individuals is low. However, the lifetime cardiovascular risk in these patients is actually high. The 2021 European Society of Cardiology guideline on cardiovascular disease prevention in clinical practice has been published. It proposed a different risk stratification and recommendation for treatment according to age group, based on the concept of avoiding undertreatment in young people and overtreatment in older persons. Although the guideline recommends age-dependent risk stratification, risk categories should not be applied to the mandatory initiation of drug treatment. In all age groups, other factors such as lifetime cardiovascular risk, treatment benefit and harm, comorbidities, frailty, and patient preferences should be considered when managing patients for primary prevention.

A New Cell Line Derived from the Caudal Fin of the Dwarf Gourami (Trichogaster lalius) and Its Susceptibility to Fish Viruses.

The detection of megalocytiviruses, especially the infectious spleen and kidney necrosis virus (ISKNV), in ornamental fish has increased with the rapid growth of the ornamental fish industry. In this study, dwarf gourami fin (DGF) cells derived from the caudal fin of the dwarf gourami (Trichogaster lalius), which is highly susceptible to red sea bream iridovirus (RSIV) and ISKNV, were established and characterized. The DGF cells were grown at temperatures ranging from 25 °C to 30 °C in Leibovitz's L-15 medium supplemented with 15% fetal bovine serum and were subcultured for more than 100 passages, predominantly with epithelial-like cells. DGF cells had a diploid chromosome number of 2n = 44. Although the initial purpose of this study was to establish a cell line for the causative agents of red sea bream iridoviral disease (RSIV and ISKNV), DGF cells were also susceptible to rhabdoviruses (viral hemorrhagic septicemia virus, hirame rhabdovirus, and spring viraemia of carp virus), exhibiting a significant cytopathic effect characterized by cell rounding and lysis. Additionally, viral replication and virion morphology were confirmed using virus-specific conventional polymerase chain reaction and transmission electron microscopy. Furthermore, both RSIV and ISKNV were replicated at high concentrations in DGF cells compared to other cell lines. Notably, the DGF cells maintained a monolayer during ISKNV infection, indicating the possibility of persistent infection. Thus, DGF can be used for viral diagnosis and may play a critical role in advancing our understanding of ISKNV pathogenesis.

Evaluation of the Horizontal Transmission of White Spot Syndrome Virus for Whiteleg Shrimp (Litopenaeus vannamei) Based on the Disease Severity Grade and Viral Shedding Rate.

White spot syndrome virus (WSSV) is the most problematic pathogen in crustaceans. In this study, we investigated the horizontal transmission model of WSSV based on the correlation between the disease severity grade and viral shedding rate and determined the minimum infective dose of WSSV via the waterborne route. Intramuscular injection challenges at different doses and water temperatures revealed that the thresholds of viral shedding and mortality were G1 (3.1 × 103 copies/mg) and G2 (8.5 × 104 copies/mg), respectively. Furthermore, a positive linear correlation was observed between viral copies of pleopods and viral shedding rate (y = 0.7076x + 1.414; p < 0.001). Minimum infective doses of WSSV were determined via an immersion challenge. Infection was observed within 1, 3, and 7 d in 105-, 103-, and 101 copies/mL of seawater, respectively. In the cohabitation challenge, infection was observed within six days with viral loads of 101 to 102 copies/mL of seawater, which further increased in the recipient group. Our results indicate a positive correlation between disease severity grade and viral shedding rate of infected shrimp and suggest that the waterborne transmission of WSSV depends on the viral load and exposure period.