Integrating Clinical, Genetic, and Electrocardiogram-Based Artificial Intelligence to Estimate Risk of Incident Atrial Fibrillation.

Background: AF risk estimation is feasible using clinical factors, inherited predisposition, and artificial intelligence (AI)-enabled electrocardiogram (ECG) analysis. Objective: To test whether integrating these distinct risk signals improves AF risk estimation. Methods: In the UK Biobank prospective cohort study, we estimated AF risk using three models derived from external populations: the well-validated Cohorts for Aging in Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) clinical score, a 1,113,667-variant AF polygenic risk score (PRS), and a published AI-enabled ECG-based AF risk model (ECG-AI). We estimated discrimination of 5-year incident AF using time-dependent area under the receiver operating characteristic (AUROC) and average precision (AP). Results: Among 49,293 individuals (mean age 65±8 years, 52% women), 825 (2.4%) developed AF within 5 years. Using single models, discrimination of 5-year incident AF was higher using ECG-AI (AUROC 0.705 [95%CI 0.686-0.724]; AP 0.085 [0.071-0.11]) and CHARGE-AF (AUROC 0.785 [0.769-0.801]; AP 0.053 [0.048-0.061]) versus the PRS (AUROC 0.618, [0.598-0.639]; AP 0.038 [0.028-0.045]). The inclusion of all components ("Predict-AF3") was the best performing model (AUROC 0.817 [0.802-0.832]; AP 0.11 [0.091-0.15], p<0.01 vs CHARGE-AF+ECG-AI), followed by the two component model of CHARGE-AF+ECG-AI (AUROC 0.802 [0.786-0.818]; AP 0.098 [0.081-0.13]). Using Predict-AF3, individuals at high AF risk (i.e., 5-year predicted AF risk >2.5%) had a 5-year cumulative incidence of AF of 5.83% (5.33-6.32). At the same threshold, the 5-year cumulative incidence of AF was progressively higher according to the number of models predicting high risk (zero: 0.67% [0.51-0.84], one: 1.48% [1.28-1.69], two: 4.48% [3.99-4.98]; three: 11.06% [9.48-12.61]), and Predict-AF3 achieved favorable net reclassification improvement compared to both CHARGE-AF+ECG-AI (0.039 [0.015-0.066]) and CHARGE-AF+PRS (0.033 [0.0082-0.059]). Conclusions: Integration of clinical, genetic, and AI-derived risk signals improves discrimination of 5-year AF risk over individual components. Models such as Predict-AF3 have substantial potential to improve prioritization of individuals for AF screening and preventive interventions.

Subcritical Water Extraction of Undaria pinnatifida: Comparative Study of the Chemical Properties and Biological Activities across Different Parts.

The subcritical water extraction of Undaria pinnatifida (blade, sporophyll, and root) was evaluated to determine its chemical properties and biological activities. The extraction was conducted at 180 °C and 3 MPa. Root extracts exhibited the highest phenolic content (43.32 ± 0.19 mg phloroglucinol/g) and flavonoid content (31.54 ± 1.63 mg quercetin/g). Sporophyll extracts had the highest total sugar, reducing sugar, and protein content, with 97.35 ± 4.23 mg glucose/g, 56.44 ± 3.10 mg glucose/g, and 84.93 ± 2.82 mg bovine serum albumin (BSA)/g, respectively. The sporophyll contained the highest fucose (41.99%) and mannose (10.37%), whereas the blade had the highest galactose (48.57%) and glucose (17.27%) content. Sporophyll had the highest sulfate content (7.76%). Key compounds included sorbitol, glycerol, L-fucose, and palmitic acid. Root extracts contained the highest antioxidant activity, with IC50 values of 1.51 mg/mL (DPPH), 3.31 mg/mL (ABTS+), and 2.23 mg/mL (FRAP). The root extract exhibited significant α-glucosidase inhibitory activity with an IC50 of 5.07 mg/mL, indicating strong antidiabetic potential. The blade extract showed notable antihypertensive activity with an IC50 of 0.62 mg/mL. Hence, subcritical water extraction to obtain bioactive compounds from U. pinnatifida, supporting their use in functional foods, cosmetics, and pharmaceuticals is highlighted. This study uniquely demonstrates the variation in bioactive compound composition and bioactivities across different parts of U. pinnatifida, providing deeper insights. Significant correlations between chemical properties and biological activities emphasize the use of U. pinnatifida extracts for chronic conditions.

Prenatal and infant exposure to antibiotics and subsequent risk of neuropsychiatric disorders in children: A nationwide birth cohort study in South Korea.

We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study(infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05-1.08]) and postnatal life (1.05 [1.03-1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09-1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05-1.08]) and severe outcomes (1.17 [1.09-1.26]), especially for intellectual disability (1.12 [1.07-1.17]), ADHD (1.10 [1.07-1.13]), anxiety (1.06 [1.02-1.11]), mood (1.06 [1.00-1.12]), and autism (1.03 [1.01-1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6-12) and 12 % (7-17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription.

Comorbid physical health outcomes in patients with bipolar disorder: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Although several meta-analyses have examined the association between bipolar disorder (BD) and its comorbid health outcomes, this evidence has not been comprehensively assembled. OBJECTIVE: We aimed to systematically review existing meta-analyses based on multiple physical outcomes and validate the evidence level by examining the existing certainty of evidence. METHODS: We systematically searched databases, including PubMed/MEDLINE, Embase, Google Scholar, and CINAHL, for articles published up to July 2023. We included meta-analyses of cohort, case-control, and/or cross-sectional studies investigating any comorbid health outcomes in patients with BD. We conducted quality assessments of the included meta-analysis using AMSTAR2. The credibility of findings was categorized into five levels of class and quality of evidence (CE), including convincing, highly suggestive, suggestive, weak, or not significant. RESULTS: We analyzed 12 meta-analyses, including 145 original articles, covering 14 unique health outcomes with over 60 million participants across 29 countries and five continents. Among 14 health outcomes, BD was significantly associated with eight comorbid health outcomes, including dementia (equivalent odds ratio [eOR], 2.96 [95 % confidence intervals {CI}, 1.69-5.17]; CE=suggestive), Parkinson's disease (3.35 [1.72-6.53]; CE=suggestive), asthma (1.86 [1.42-2.42]; CE=weak), toxoplasmosis (1.69 [1.21-2.37]; CE=weak), hypertension (1.28 [1.02-1.60]; CE=convincing), breast cancer (1.33 [1.15-1.55]; CE=weak), obesity (1.64 [1.30-1.99]; CE=suggestive), and type 2 diabetes mellitus (1.98 [1.55-2.52]; CE=weak). CONCLUSION: Individuals with BD are predisposed to numerous comorbid physical conditions, though these links are supported by various evidence levels and necessitate further studies. It is imperative that physicians be aware of these potential comorbidities in patients with BD and take proactive measures to manage them.

Comorbid health conditions in people with attention-deficit/hyperactivity disorders: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: We aimed to systematically review meta-analyses on the link between attention-deficit/hyperactivity disorder (ADHD) and a broad range of psychiatric, physical, and behavioral health conditions (PROSPERO; no.CRD42023448907). RESULTS: We identified 22 meta-analyses that included 544 primary studies, covering 76 unique conditions in over 234 million participants across 36 countries and six continents. We found high-certainty evidence for the associations between ADHD and neuropsychiatric conditions (bipolar disorders, personality disorders, schizophrenia, and pragmatic language skills), night awakenings, obesity, decayed incipient surfaces, asthma, astigmatism, hyperopia and hypermetropia, strabismus, and suicide ideation. Moderate-certainty evidence suggested that ADHD was associated with headache, mood/affective disorders, depression, bruxism, bone fractures, atopic rhinitis, vision problems, suicide attempts, completed suicide, and all-cause mortality. Low-certainty evidence indicated associations with eating disorders, sleep efficiency, type 2 diabetes, dental trauma prevalence, atopic diseases, and atopic dermatitis. Very low-certainty evidence showed associations between ADHD and several sleep parameters. CONCLUSION: We found varied levels of evidence for the associations of ADHD with multiple health conditions. Therefore, clinicians should consider a wide range of neurological, psychiatric, sleep and suicide-related, metabolic, musculoskeletal, oral, allergic, and visual conditions, as well as the increased risk of mortality when assessing individuals with ADHD.

Cardiovascular and cerebrovascular adverse events associated with intravitreal anti-vascular endothelial growth factor monoclonal antibodies: a World Health Organization pharmacovigilance study.

PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SUBJECTS: VigiBase, a World Health Organization (WHO) global safety report database DESIGN: Pharmacovigilance study METHODS: The individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 23,129 ADRs after intravitreal anti-VEGF therapy and 25,015,132 ADRs associated with any drug (full database). MAIN OUTCOME MEASURES: The reporting odds ratio (ROR) and information components (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd ratio (rOR). RESULTS: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI 1.70-1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI 1.47-1.77]), arrythemias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 >0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI 4.82-5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI 22.10-24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI 3.98-6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI 5.03-5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI 4.14-5.6]). Inter-drug comparison indicated that compared to ranibizumab, patients with aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI 0.40-0.65]). CONCLUSIONS: In this pharmacovigilance case-noncase study, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept.

Association of genetic risk, lifestyle, and their interaction with obesity and obesity-related morbidities.

The extent to which modifiable lifestyle factors offset the determined genetic risk of obesity and obesity-related morbidities remains unknown. We explored how the interaction between genetic and lifestyle factors influences the risk of obesity and obesity-related morbidities. The polygenic score for body mass index was calculated to quantify inherited susceptibility to obesity in 338,645 UK Biobank European participants, and a composite lifestyle score was derived from five obesogenic factors (physical activity, diet, sedentary behavior, alcohol consumption, and sleep duration). We observed significant interaction between high genetic risk and poor lifestyles (pinteraction < 0.001). Absolute differences in obesity risk between those who adhere to healthy lifestyles and those who do not had gradually expanded with an increase in polygenic score. Despite a high genetic risk for obesity, individuals can prevent obesity-related morbidities by adhering to a healthy lifestyle and maintaining a normal body weight. Healthy lifestyles should be promoted irrespective of genetic background.

National and Regional Trends in the Prevalence of Hypertension in South Korea Amid the Pandemic, 2009-2022: Nationwide Study of Over 3 Million Individuals.

BACKGROUND: Understanding the association between hypertension prevalence and socioeconomic and behavioral variables during a pandemic is essential, and this analysis should extend beyond short-term trends. OBJECTIVE: This study aims to examine long-term trends in the prevalence of participants diagnosed with and receiving treatment for hypertension, using data collected by a nationally representative survey from 2009 to 2022, which includes the COVID-19 pandemic era. METHODS: A nationwide, population-based, cross-sectional study used data collected from the South Korea Community Health Survey between 2009 and 2022. The study sample comprised 3,208,710 Korean adults over a period of 14 years. We aimed to assess trends in the prevalence of participants diagnosed with and receiving treatment for hypertension in the national population from 2009 to 2022, with a specific focus on the COVID-19 pandemic, using weighted linear regression models. RESULTS: Among the included 3,072,546 Korean adults, 794,239 (25.85%) were aged 19-39 years, 1,179,388 (38.38%) were aged 40-59 years; 948,097 (30.86%) were aged 60-79 years, and 150,822 (4.91%) were aged 80 years or older. A total of 1,426,379 (46.42%) were men; 761,896 (24.80%) and 712,264 (23.18%) were diagnosed with and received treatment for hypertension, respectively. Although the overall prevalence over the 14-year period increased, the upward trends of patients diagnosed with and receiving treatment for hypertension decreased during the COVID-19 pandemic era compared with the prepandemic era (ß difference for trend during vs before the pandemic -.101, 95% CI -0.107 to -0.094 vs -.133, 95% CI -0.140 to -0.127). Notably, the trends in prevalence during the pandemic were less pronounced in subgroups of older adults (≥60 years old) and individuals with higher alcohol consumption (≥5 days/month). CONCLUSIONS: This nationwide representative study found that the national prevalence of participants diagnosed with and receiving treatment for hypertension increased during the prepandemic era. However, there was a marked decrease in these trends during the prepandemic era, compared with the pandemic era, particularly among specific subgroups at increased risk of negative outcomes. Future studies are needed to evaluate the factors associated with changes in the prevalence of hypertension during the COVID-19 pandemic.

National trends in sexual intercourse and usage of contraception among Korean adolescents.

BACKGROUND: The exact influence of the COVID-19 pandemic on sexual intercourse and usage of contraception remains largely uncharted territory. To bridge this gap in knowledge, we conducted a comprehensive, cross-sectional examination of long-term trends in the prevalence of sexual intercourse and usage of contraception among South Korean adolescents from 2006 to 2022. METHODS: In our research, we drew upon data encompassing 1,138,799 South Korean adolescents aged 12 to 18 years, derived from the Korean Youth Risk Behavior Web-based Survey (KYRBS) over a period spanning from 2006 to 2022. We focused on the prevalence of sexual intercourse, contraception utilization, and the underlying associated factors among this demographic. The KYRBS data was collected using a complex sampling strategy to determine the national prevalence estimates and shifts in prevalence before (2006-2019) and during (2020-2022) the COVID-19 pandemic era. RESULTS: During the pre-pandemic period, a decrease in adolescent sexual intercourse was observed (6.34% in 2006, 5.53% in 2012, and 5.87% in 2019). However, in the post-pandemic period (2020-2022), there was a surge in sexual intercourse (4.55% in 2020 and 6.20% in 2022). This evident alteration in sexual intercourse trajectory between pre- and post-pandemic periods was statistically significant [ßdiff, 0.950; 95% confidence interval (CI), 0.756-1.144]. Regarding contraceptive use among South Korean adolescents, there was an increase in the pre-COVID-19 pandemic phase across all demographic segments (14.61% in 2006, 22.30% in 2012, and 47.69% in 2022) but a notable decline when compared with the pre- and post-pandemic periods (ßdiff, - 0.319; 95% CI, - 0.454 to - 0.184). Additionally, during the study period, a decrease in sexual intercourse was observed in the pre-pandemic period (ß, - 0.129; 95% CI, - 0.148 to - 0.110), followed by an increase in the post-pandemic period (ß, 0.821; 95% CI, 0.627 to 1.014). This shift is highlighted by an effect size of 0.96 [weighted odds ratio (wOR); 95% CI, 0.92 to 1.00], indicating a substantial change in adolescent sexual behaviors across study periods. CONCLUSIONS: The increase in sexual intercourse and decrease in usage of contraception observed in our study between the pre- and post-COVID-19 periods suggests a potential threat to sexual health among South Korean adolescents. This trend emphasizes the ongoing necessity of raising awareness about adolescent sexual behavior in South Korea.

Predictive Geogenic Radon Potential (P-GRP): A novel approach for comprehensive hazard assessment and risk modeling in subsurface environment.

Geogenic radon potential (GRP) is traditionally used for mapping radon-prone areas. However, this has challenges in the accurate assessment of radon risk because of limitations such as oversimplified soil measurements and lack of geological profiles. This study presents predictive geogenic radon potential (P-GRP), integrating geological characterization and advanced modeling for the emanation and transport of radon in the subsurface environment. Seoul, South Korea, was selected as the research area for the evaluation of hazards using P-GRP, while subway station A was selected for the assessment of indoor health risks. The geology was characterized by the layers of bedrock and soil using uranium contents and porosity. The emanation of radon was modeled considering the radioactive decay chain of uranium and the pore structures. The vertical transport of radon was modeled considering the porosity variation within geological media, which was used for the calculation of P-GRP. Without loss of continuity, the P-GRP map was constructed by calculating P-GRP at a specific depth over the Seoul area. The calculation of P-GRP in the case of subway station A demonstrates that the radon concentration in the bedrock at the platform depth was expected to be 382 million Bqm-3. The indoor radon risk was calculated using the P-GRP by coupling the vapor intrusion process. This presented a high cancer risk for the employees as well as commuters. The P-GRP map of Seoul demonstrated higher hazards in granite zones compared to banded gneiss zones. These results have demonstrated that the P-GRP could be a novel and promising approach for assessing hazard and risk by geogenic radon during subsurface development.

Small Peptide Derived from SFRP5 Suppresses Melanogenesis by Inhibiting Wnt Activity.

Melanocytes, located in the epidermis' basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and ß-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and ß-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.

In Vitro Metabolism and Transport Characteristics of Zastaprazan.

Zastaprazan (JP-1366), a novel potassium-competitive acid blocker, is a new drug for the treatment of erosive esophagitis. JP-1366 is highly metabolized in human, mouse, and dog hepatocytes but moderately metabolized in rat and monkey hepatocytes when estimated from the metabolic stability of this compound in hepatocyte suspension and when 18 phase I metabolites and 5 phase II metabolites [i.e., N-dearylation (M6), hydroxylation (M1, M19, M21), dihydroxylation (M7, M8, M14, M22), trihydroxylation (M13, M18), hydroxylation and reduction (M20), dihydroxylation and reduction (M9, M16), hydrolysis (M23), hydroxylation and glucuronidation (M11, M15), hydroxylation and sulfation (M17), dihydroxylation and sulfation (M10, M12), N-dearylation and hydroxylation (M3, M4), N-dearylation and dihydroxylation (M5), and N-dearylation and trihydroxylation (M2)] were identified from JP-1366 incubation with the hepatocytes from humans, mice, rats, dogs, and monkeys. Based on the cytochrome P450 (CYP) screening test and immune-inhibition analysis with CYP antibodies, CYP3A4 and CYP3A5 played major roles in the metabolism of JP-1366 to M1, M3, M4, M6, M8, M9, M13, M14, M16, M18, M19, M21, and M22. CYP1A2, 2C8, 2C9, 2C19, and 2D6 played minor roles in the metabolism of JP-1366. UDP-glucuronosyltransferase (UGT) 2B7 and UGT2B17 were responsible for the glucuronidation of M1 to M15. However, JP-1366 and active metabolite M1 were not substrates for drug transporters such as organic cation transporter (OCT) 1/2, organic anion transporter (OAT) 1/3, organic anion transporting polypeptide (OATP)1B1/1B3, multidrug and toxic compound extrusion (MATE)1/2K, P-glycoprotein (P-gp), and breast cancer-resistant protein (BCRP). Only M1 showed substrate specificity for P-gp. The findings indicated that drug-metabolizing enzymes, particularly CYP3A4/3A5, may have a significant role in determining the pharmacokinetics of zastaprazan while drug transporters may only have a small impact on the absorption, distribution, and excretion of this compound.

Therapeutic Effect of Anti-Inflammatory Tripeptide Cream in Hand-Foot Syndrome/Skin Reaction Related to Anticancer Drugs: a Randomized, Double-Blind, Placebo-Controlled Pilot Trial.

Purpose: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist BinterinTM and the Wnt-antagonist WinhibinTM. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs. Materials and Methods: This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to nine weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR. Results: Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance. Conclusion: Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs.

Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan.

We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.

Effects and safety of transcranial direct current stimulation on multiple health outcomes: an umbrella review of randomized clinical trials.

Transcranial direct current stimulation (tDCS), which delivers a direct current to the brain, emerged as a non-invasive potential therapeutic in treating a range of neurological and neuropsychiatric disorders. However, a comprehensive quantitative evidence synthesis on the effects of tDCS on a broad range of mental illnesses is lacking. Here, we systematically assess the certainty of the effects and safety of tDCS on several health outcomes using an umbrella review of randomized controlled trials (RCTs). The methodological quality of each included original meta-analysis was assessed by the A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2), and the certainty of the evidence for each effect was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). We followed an a priori protocol (PROSPERO CRD42023458700). We identified 15 meta-analyses of RCTs (AMSTAR 2; high 3, moderate 3, and low 9) that included 282 original articles, covering 22 unique health endpoints across 22 countries and six continents. From meta-analyses of RCTs supported by very low to high certainty of evidence, it was found that tDCS improved symptoms related to post-stroke, including post-stroke depression scale score (equivalent standardized mean difference [eSMD], 1.61 [95% confidence level, 0.72-2.50]; GRADE=moderate), activities of daily living independence (7.04 [3.41-10.67]; GRADE=high), motor recovery of upper and lower extremity (upper extremity: 0.15 [0.06-0.24], GRADE=high; lower extremity: 0.10 [0.03-0.16], GRADE=high), swallowing performance (GRADE=low), and spasticity (GRADE=moderate). In addition, tDCS had treatment effects on symptoms of several neurological and neuropsychiatric disorders, including obsessive-compulsive disorder (0.81 [0.44-1.18]; GRADE=high), pain in fibromyalgia (GRADE=low), disease of consciousness (GRADE=low), insight score (GRADE=moderate) and working memory (0.34 [0.01-0.67]; GRADE=high) in schizophrenia, migraine-related pain (-1.52 [-2.91 to -0.13]; GRADE=high), attention-deficit/hyperactivity disorder (reduction in overall symptom severity: 0.24 [0.04-0.45], GRADE=low; reduction in inattention: 0.56 [0.02-1.11], GRADE=low; reduction in impulsivity: 0.28 [0.04-0.51], GRADE=low), depression (GRADE=low), cerebellar ataxia (GRADE=low), and pain (GRADE=very low). Importantly, tDCS induced an increased number of reported cases of treatment-emergent mania or hypomania (0.88 [0.62-1.13]; GRADE=moderate). We found varied levels of evidence for the effects of tDCS with multiple neurological and neuropsychiatric conditions, from very low to high certainty of evidence. tDCS was effective for people with stroke, obsessive-compulsive disorder, fibromyalgia, disease of consciousness, schizophrenia, migraine, attention-deficit/hyperactivity disorder, depression, cerebellar ataxia, and pain. Therefore, these findings suggest the benefit of tDCS for several neurological and neuropsychiatric disorders; however, further studies are needed to understand the underlying mechanism and optimize its therapeutic potential.

National prevalence of atopic dermatitis in Korean adolescents from 2009 to 2022.

Previous studies have examined the prevalence of allergic diseases in adolescents 1-2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the ß difference (ßdiff) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66-6.91) in 2009-2011 to 6.89% (95% CI 6.72-7.05) in 2018-2019, then decreased slightly to 5.82% (95% CI 5.60-6.04) in 2022. Across the 14 years, middle school student status, low parent's highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic.

Acute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan.

Considering the significant burden of post-acute COVID-19 conditions among patients infected with SARS-CoV-2, we aimed to identify the risk of acute respiratory complications or post-acute respiratory sequelae. A binational population-based cohort study was conducted to analyze the risk of acute respiratory complications or post-acute respiratory sequelae after SARS-CoV-2 infection. We used a Korean nationwide claim-based cohort (K-COV-N; n = 2,312,748; main cohort) and a Japanese claim-based cohort (JMDC; n = 3,115,606; replication cohort) after multi-to-one propensity score matching. Among 2,312,748 Korean participants (mean age, 47.2 years [SD, 15.6]; 1,109,708 [48.0%] female), 17.1% (394,598/2,312,748) were infected with SARS-CoV-2. The risk of acute respiratory complications or post-acute respiratory sequelae is significantly increased in people with SARS-CoV-2 infection compared to the general population (acute respiratory complications: HR, 8.06 [95% CI, 6.92-9.38]; post-acute respiratory sequelae: 1.68 [1.62-1.75]), and the risk increased with increasing COVID-19 severity. We identified COVID-19 vaccination as an attenuating factor, showing a protective association against acute or post-acute respiratory conditions. Furthermore, while the excess post-acute risk diminished with time following SARS-CoV-2 infection, it persisted beyond 6 months post-infection. The replication cohort showed a similar pattern in the association. Our study comprehensively evaluates respiratory complications in post-COVID-19 conditions, considering attenuating factors such as vaccination status, post-infection duration, COVID-19 severity, and specific respiratory conditions.

National trends in counseling for stress and depression and COVID-19 pandemic-related factors among adults, 2009-2022: A nationwide study in South Korea: Stress, depression, and pandemic.

To investigate the long-term trends in counseling for stress and depression using data from a nationwide survey in South Korea. We conducted a nationwide serial, large-scale, cross-sectional, survey-based study using data from 2,903,887 Korean adults from the Korea Community Health Survey, 2009-2022. Our study investigated the trends and risk factors for counseling for stress and depression during the pre-pandemic (2009-2019) and pandemic era (2020-2022). The prevalence of counseling for stress and depression increased across pre-pandemic (counseling for stress: ß, 0.217 [95 % CI, 0.194 to 0.241]; counseling for depression: ß, 0.136 [0.118 to 0.154]) and pandemic periods (ß, 0.324 [0.287 to 0.360]; ß, 0.210 [0.182 to 0.239], respectively). The prevalence of counseling for stress and depression showed steeper slopes for increasing trends after the outbreak. In addition, subgroups with female sex, urban residence, lower household income, lower self-rated health, shorter sleep time, and higher worries about contracting COVID-19 were the risk factors associated with the increased prevalence of counseling for stress and depression. Our study analyzed the trends in counseling for stress and depression among over two million South Korean adults in 2009-2022, revealing a significant escalation during the pandemic. These findings emphasize the need for mental health policies to support vulnerable groups during the pandemic.

Internet of Things-Enabled Patch With Built-in Microsensors and Wireless Chip: Real-Time Remote Monitoring of Patch Treatment.

Purpose: We aimed to design, develop, and evaluate an internet of things-enabled patch (IoT patch) for real-time remote monitoring of adherence (or patch wear time) during patch treatment in child participants in clinical trials. This study provides healthcare providers with a tool for objective, real-time, and remote assessment of adherence and for making required adjustments to treatment plans. Methods: The IoT patch had two temperature microsensors and a wireless chip. One sensor was placed closer to the skin than the other, resulting in a temperature difference depending on whether the patch was worn. When the patch was worn, it measured temperatures every 30 seconds and transmitted temperature data to a cloud server via a mobile application every 15 seconds. The patch was evaluated via 2 experiments with 30 healthy adults and 40 children with amblyopia. Results: Excellent monitoring accuracy was observed in both adults (mean delay of recorded time data, 0.4 minutes) and children (mean, 0.5 minutes). The difference between manually recorded and objectively recorded patch wear times showed good agreement in both groups. Experiment 1 showed accurate monitoring over a wide range of temperatures (from 0 to 30°C). Experiment 2 showed no significant differences in wearability (ease-of-use and comfort scores) between the IoT and conventional patches. Conclusions: The IoT patch offers an accurate, real-time, and remote system to monitor adherence to patch treatment. The patch is comfortable and easy to use. The utilization of an IoT patch may increase adherence to patch treatment based on accurate monitoring. Translational Relevance: Results show that the IoT patch can enable real-time adherence monitoring in clinical trials, improving treatment precision, and patient compliance to enhance outcomes.

Antimicrobial activity of ceftazidime-avibactam against KPC-2-producing Enterobacterales: a cross-combination and dose-escalation titration study with relebactam and vaborbactam.

With the introduction of ceftazidime-avibactam worldwide, the antimicrobial activity of new ß-lactam/ß-lactamase inhibitors (BL/BLIs) needs to be investigated. From January 2020 to June 2023, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were collected. With a broth microdilution test of new BL/BLIs, cross-activity test with nine combinations of BLs and new BLIs and dose-escalation titration test for non-susceptible isolates were conducted to investigate inhibitory activities of new BLIs. A total of 188 isolates was collected and most isolates (186/188, 98.9%) carried the KPC-2 gene exclusively, while two isolates (1.1%) co-harbored NDM-1. Among the 186 KPC-2-producing isolates, 184 (98.9%) were susceptible to ceftazidime-avibactam, 173 (93.0%) to imipenem-relebactam, and 184 (98.9%) to meropenem-vaborbactam. All isolates non-susceptible to imipenem-relebactam or meropenem-vaborbactam became susceptible when avibactam replaced relebactam or vaborbactam, with 7 of 11 (63.6%) imipenem-relebactam non-susceptible isolates and both (100.0%) of the meropenem-vaborbactam non-susceptible isolates. When the minimum inhibitory concentrations (MICs) of BLs were compared using log2 scales, combinations with avibactam showed statistically significant efficacy in lowering MICs compared to relebactam and vaborbactam (all P < 0.05). In the dose-escalation test of new BLIs, increasing dose of all new BLIs corresponded to increased susceptibility to BLs. Ceftazidime-avibactam exhibited excellent susceptibility against KPC-2-producing Enterobacterales unless co-harboring metallo-ß-lactamase. The cross-combination test against non-susceptible isolates suggests that the inhibitory activity of avibactam was superior to those of relebactam or vaborbactam. Increasing the dose of new BLIs produced increased susceptibility to BLs, suggesting that high-concentration regimen need to be developed. IMPORTANCE: This study investigated 188 Klebsiella pneumoniae carbapenemase (KPC)-2-producing Enterobacterales collected from January 2020 to June 2023 in a tertiary care hospital of Korea. Most isolates were susceptible to ceftazidime-avibactam (98.9%) and meropenem-vaborbactam (98.9%), while susceptibility to imipenem-relebactam was lower (93.0%). The cross-combination test using nine combinations of the individual ß-lactams (BLs) and new ß-lactamase inhibitors (BLIs) showed that the inhibitory activity of avibactam was significantly superior to relebactam or vaborbactam when the Log2 MIC of BLs were compared for each combination with BLIs (all P < 0.05). The dose-escalation test of new BLIs demonstrated that increasing doses of new BLIs corresponded to increased susceptibility to BLs. Taken together, this study illustrates the excellent activity of ceftazidime-avibactam against KPC-2-producing Enterobacterales and suggests further investigation into high-concentration regimens for potentially non-susceptible clinical isolates.