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Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4+ T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001's safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.
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BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).
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Introduction: Dupilumab is the first biological treatment for atopic dermatitis (AD). Dupilumab-associated ocular surface disease (DAOSD) is one of the most commonly reported side effects in patients with AD during dupilumab treatment. This study aimed to identify risk factors for DAOSD in a real-world setting and construct a risk-scoring system for predicting DAOSD risk. Methods: A retrospective analysis was conducted for dupilumab-treated adult patients with AD between April 2019 and September 2023 at Yeouido St. Mary's Hospital in Korea. Patients aged ≥18 years who received dupilumab to treat AD were included. Univariate and multivariable logistic regression analyses were performed to determine independent risk factors for DAOSD. A risk scoring system was constructed to predict DAOSD risk based on the adjusted odd ratios of significant variables. Results: Of the 97 dupilumab-treated patients, 28 (28.9%) developed DAOSD. Among them, three (10.7%) patients discontinued dupilumab due to ocular side effects. In the multivariable analysis, older age, history of conjunctivitis, and a baseline Eczema Area and Severity Index (EASI) score ≥28 were independent risk factors for developing DAOSD. Using these variables, a risk-scoring system was constructed. The predicted DAOSD risks for AD patients with 0, 1, 2, 3, 4, and 5 points were 5.8%, 14.2%, 30.7%, 54.3%, 76.2%, and 89.6%, respectively. Conclusion: In this study, the patient's age, history of conjunctivitis, and higher baseline EASI score were significantly associated with DAOSD. This risk-scoring system would help identify high-risk patients requiring more caution when initiating dupilumab treatment.
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The tribological properties of 19 commercial food products, grouped into six categories (yogurt, dressings, spreads, porridges, emulsified sauces, and syrups) were investigated in relation to their rheological (dynamic oscillatory shear test) and nutritional properties (fat, carbohydrate, and protein). A tribological system (a glass ball and three polydimethylsiloxane pins) generated the extended Stribeck curve, monitoring friction factors (f) over an extended range of sliding speed (v) (10-8 to 100 m/s). Tribological parameters (f, v) at four inflection points dividing the frictional regimes (X1, breakaway point between the static and kinetic regimes; X1-X2, boundary; X2-X3, mixed; X3-X4, hydrodynamic regimes) and the slope between X3 and X4 (s) were subjected to principal component analysis and hierarchical clustering on principal components, using rheological and nutritional parameters as quantitative supplementary variables. Tribological patterns were predominantly influenced by viscosity, viscoelasticity, yield stress, fat content, and the presence of particles (e.g., sugar, proteins, and fibers) and pasting materials (e.g., starches and modified starches). The 19 tribological patterns were classified into 3 clusters: low f and s for fat- and/or viscoelastic-dominant foods (Cluster 1), low f and high s for food emulsions and/or those with low extent of shear-thinning (Cluster 2), and high f at the boundary regime either for the most viscous foods or for those in the presence of particulates (Cluster 3). These results suggest that the compositional and rheological properties have a more profound impact on the classification of complex tribological patterns than the categories of food products.
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Valor Nutritivo , Reologia , Viscosidade , Elasticidade , Alimentos , Fricção , Análise de Alimentos , Análise de Componente PrincipalRESUMO
For the protection of human health and environment, there is a growing demand for high-performance, user-friendly biosensors for the prompt detection of pathogenic bacteria in samples containing various substances. We present a nanogap electrode-based purely electrical impedimetric sensor that utilizes the dielectrophoresis (DEP) mechanism. Our nanogap sensor can directly and sensitively detect pathogens present at concentrations as low as 1-10 cells/assay in buffers and drinking milk without the need for separation, purification, or specific ligand binding. This is achieved by minimizing the electrical double-layer effect and electrode polarization in nanogap impedance sensors, reducing signal loss. In addition, even at low DEP voltages, nanogap sensors can quickly establish strong DEP forces between the nanogap electrodes to control the spatial concentration of pathogens around the electrodes. This activates and stabilizes inter-electrode signal transmission along the nanogap-aligned pathogens, increasing sensitivity and reducing errors during repeated measurements. The DEP-enabled nanogap impedance sensor developed in this study is valuable for a variety of pathogen detection and monitoring systems including point-of-care testing (POCT) as it can detect pathogens in diverse samples containing multiple substances quickly and with high sensitivity, is compatible with complex solutions such as food and beverages, and provides highly reproducible results without the need for separate binding and separation processes.
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Older Korean immigrants are one of the most understudied and marginalized Asian ethnic groups in the United States, despite their rapid population growth. Many older Korean immigrants encounter distinct challenges in assimilating into their new country as first-generation immigrants, including cultural conflict, language barriers, low economic status, and a lack of social support. These issues may be compounded for those who live alone, which is considered a negative factor in their mental and physical health. However, little is known about the correlates and health issues of older Korean immigrants living alone. This study's objective was to explore correlates and health issues among older Korean immigrants living alone. Based on established scoping review methodology five databases, CINAHL, PubMed, MEDLINE, SocINDEX, and Health Source Nursing/Academic Edition, were used to find relevant studies. Twelve articles were reviewed, and four major themes were identified as correlates and health issues among older Korean immigrants living alone in the United States: depression, changed family relationships, social interactions, and factors on general health and well-being. The findings have significant implications for healthcare professionals for understanding the unique culture, situation, and physical and psychosocial vulnerability of older Korean immigrants living alone.
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BACKGROUND: It is unclear how exposure to and perception of community trauma creates a mental health burden. This study aimed to examine the psychological distress trends among community residents in acute stress reaction, acute stress disorder, and post-traumatic stress disorder phases following the Seoul Halloween crowd crush. METHODS: A three-wave repeated cross-sectional survey was conducted with participants after the incident. Analysis of covariance (ANCOVA) with post hoc Bonferroni test was adopted to examine temporal changes in psychological distress and psychological outcomes resulting from media impacts. A two-way ANCOVA was adopted to examine the interaction effects of time and relevance to victims on psychological distress. RESULTS: A total of 807, 1,703, and 2,220 individuals participated in the three waves. Anxiety (estimated mean [standard error of the mean]: 2.28 [0.03] vs. 2.12 [0.02] vs. 2.03 [0.02]; P < 0.001), depression (2.22 [0.03] vs. 2.01 [0.02] vs. 1.90 [0.02]; P < 0.001), and anger (2.70 [0.03] vs. 2.66 [0.02] vs. 2.49 [0.02]; P < 0.001) gradually improved. However, sense of safety initially worsened and did not recover well (2.96 [0.03] vs. 2.75 [0.02] vs. 2.77 [0.02]; P < 0.001). The interaction effect of time and relevance to the victim were significant in depression (P for interaction = 0.049), anger (P for interaction = 0.016), and sense of safety (P for interaction = 0.004). Among participants unrelated to the victim, those exposed to graphics exhibited higher levels of anxiety (2.09 [0.02] vs. 1.87 [0.07]; P = 0.002), depression (1.99 [0.02] vs. 1.83 [0.07]; P = 0.020), and anger (2.71 [0.03] vs. 2.47 [0.08]; P = 0.003) at W2 and higher anger (2.49 [0.02] vs. 2.31 [0.06]; P = 0.005) at W3. CONCLUSION: Community residents indirectly exposed to trauma also experienced psychological distress in the early stages after the incident. A significant impact of media which might have served as a conduit for unfiltered graphics and rumors was also indicated.
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Ansiedade , Depressão , Transtornos de Estresse Pós-Traumáticos , Humanos , Masculino , Feminino , Estudos Transversais , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Pessoa de Meia-Idade , Angústia Psicológica , Inquéritos e Questionários , Seul/epidemiologia , Meios de Comunicação de Massa , Ira , Transtornos de Estresse Traumático Agudo/psicologia , Adulto Jovem , Idoso , Exposição à MídiaRESUMO
BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.
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Atorvastatina , Doença da Artéria Coronariana , Diabetes Mellitus , Inibidores de Hidroximetilglutaril-CoA Redutases , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/efeitos adversos , Rosuvastatina Cálcica/uso terapêutico , Atorvastatina/efeitos adversos , Atorvastatina/uso terapêutico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Feminino , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Incidência , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Biomarcadores/sangue , Medição de RiscoRESUMO
Purpose: This study aimed to develop the Health Belief Model scale for premature birth prevention (HBM-PBP) and evaluated its psychometric properties in women of childbearing age. Methods: This study employed a cross-sectional design and included 724 women of childbearing age with intentions of future childbirth or in their first trimester of pregnancy. An item pool was formulated from the literature and in-depth interviews based on the health belief model. Content validation was conducted by experts and through cognitive interviews with women of childbearing age. Construct and concurrent validity and reliability were evaluated using factor analysis, Pearson's correlation analysis, and Cronbach's alpha. Results: The HBM-PBP consisted of 96 items, including perceived susceptibility (21 items, 5 subscales), severity (26 items, 5 subscales), benefits (27 items, 5 subscales), and barriers (22 items, 5 subscales). Convergent and discriminant validity were supported. The Cronbach's alpha coefficient of the domains ranged from 0.87 to 0.94. Conclusion: The HBM-PBP is a valid and reliable measurement scale with good psychometric properties. It can be used to measure health beliefs in women, either as a whole or in individual domains. Health professionals can leverage the HBM-PBP to discern women's health beliefs on premature birth, facilitating tailored interventions and educational efforts.
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Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger ß1 integrin activation and instead actuate a TGF-ß1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.
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Apoptose , Sobrevivência Celular , Fibroblastos , Metaloproteinase 14 da Matriz , Animais , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/genética , Fibroblastos/metabolismo , Camundongos , Camundongos Knockout , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Integrina beta1/metabolismo , Integrina beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Derme/metabolismo , Derme/citologia , Células Cultivadas , Matriz Extracelular/metabolismo , Camundongos Endogâmicos C57BL , Pele/metabolismoRESUMO
Toll-like receptors (TLRs) are critical components to stimulate immune responses against various infections. Recently, TLR agonists have emerged as a promising way to activate anti-tumor immunity. L-pampo, a TLR1/2 and TLR3 agonist, induces humoral and cellular immune responses and also causes cancer cell death. In this study, we investigated the L-pampo-induced signals and delineated their interactions with molecular signaling pathways using RNA-seq in immune cells and colon and prostate cancer cells. We first constructed a template network with differentially expressed genes and influential genes from network propagation using the weighted gene co-expression network analysis. Next, we obtained perturbed modules using the above method and extracted core submodules from them by conducting Walktrap. Finally, we reconstructed the subnetworks of major molecular signals utilizing a shortest path-finding algorithm, TOPAS. Our analysis suggests that TLR signaling activated by L-pampo is transmitted to oxidative phosphorylation (OXPHOS) with reactive oxygen species (ROS) through PI3K-AKT and JAK-STAT only in immune and prostate cancer cells that highly express TLRs. This signal flow may further sensitize prostate cancer to L-pampo due to its high basal expression level of OXPHOS and ROS. Our computational approaches can be applied for inferring underlying molecular mechanisms from complex gene expression profiles.
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Redes Reguladoras de Genes , Transdução de Sinais , Receptores Toll-Like , Humanos , Receptores Toll-Like/agonistas , Receptores Toll-Like/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Fosforilação Oxidativa , Agonistas do Receptor Semelhante a TollRESUMO
BACKGROUND: Mobocertinib, an EGFR exon 20 insertion (Ex20ins)-specific tyrosine kinase inhibitor has been used for treatment of advanced/metastatic EGFR Ex20ins-mutant non-small cell lung cancer (NSCLC). However, resistance mechanisms to EGFR Ex20ins-specific inhibitors and the efficacy of subsequent amivantamab treatment is unknown. METHODS: To investigate resistance mechanisms, tissue and cfDNA samples were collected before treatment initiation and upon development of resistance from NSCLC patients with EGFR Ex20ins mutations received mobocertinib, poziotinib, and amivantamab treatments. Genetic alterations were analyzed using whole-genome and targeted sequencing, and in vitro resistant cell lines were generated for validation. RESULTS: EGFR amplification (n = 6, including 2 broad copy number gain) and EGFR secondary mutation (n = 3) were observed at the resistance of mobocertinib. One patient had both EGFR secondary mutation and high EGFR focal amplification. In vitro models harboring EGFR alterations were constructed to validate resistance mechanisms and identify overcoming strategies to resistance. Acquired EGFR-dependent alterations were found to mediate resistance to mobocertinib in patients and in vitro models. Furthermore, two of six patients who received sequential amivantamab followed by an EGFR tyrosine kinase inhibitor had MET amplification and showed partial response. CONCLUSIONS: Our study revealed EGFR-dependent and -independent mechanisms of mobocertinib resistance in patients with advanced EGFR Ex20ins-mutant NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Éxons , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mutagênese Insercional , Mutação , /uso terapêuticoRESUMO
Background: The alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds. Methods: To determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases. Results: We observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10-21. Conclusions: We suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.
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Background and Objectives: Obstructive sleep apnea (OSA) is common in cardiovascular disease (CVD), although positive airway pressure (PAP) treatment has not been demonstrated to improve the cardiovascular outcome. The objective of this study is to investigate the impact of adherence to PAP therapy on cardiopulmonary exercise testing (CPET) performance in patients with concomitant OSA and CVD. Materials and Methods: This preliminary study involved symptomatic OSA patients requiring PAP treatment who had CVD. All subjects underwent polysomnography, echocardiography, and CPET at baseline. After 6 to 12 months of PAP treatment, CPET performance was re-assessed. The changes in CPET parameters before and after PAP treatment were compared between patients who were adherent to PAP and patients who were not adherent to PAP. Results: A total of 16 OSA patients with an apnea-hypopnea index of 32.0 ± 23.4 were enrolled. Patients were classified into the adherent (n = 9) and non-adherent (n = 7) groups with regard to PAP adherence. After 6 to 12 months of PAP treatment, the PAP-adherent group showed a greater increase in peak VO2 than the PAP-non-adherent group, but the difference between the two groups was not significant (p = 0.581). The decrease in ventilatory equivalent for the carbon dioxide slope (VE/VCO2) was significantly greater in the PAP-adherent group compared to the PAP-non-adherent group (p = 0.030). Conclusions: Adherence to PAP therapy for OSA is associated with an improvement in the VE/VCO2 slope, as an index of the ventilatory response to exercise, in patients with CVD. Screening for sleep apnea in CVD patients may be warranted, and strategies to optimize adherence to PAP in these patients are beneficial. Further evidence is needed to elucidate whether CPET could be routinely used to monitor treatment responses of OSA to PAP therapy in patients with CVD.
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Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Teste de Esforço , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/complicações , Teste de Esforço/métodos , Aptidão Cardiorrespiratória/fisiologia , Polissonografia/métodos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Idoso , Adulto , Cooperação do Paciente/estatística & dados numéricosRESUMO
BACKGROUND: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). METHODS: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. RESULTS: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). CONCLUSIONS: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579499.
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LDL-Colesterol , Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Masculino , Feminino , LDL-Colesterol/sangue , Resultado do Tratamento , Fatores Etários , Idoso de 80 Anos ou mais , Fatores de Risco , Biomarcadores/sangue , Pessoa de Meia-Idade , Fatores de Tempo , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND AND AIM: Corticosteroid use is a risk factor for avascular necrosis (AVN) and inflammatory bowel disease (IBD) patients are often exposed to higher corticosteroid usage. We investigated the epidemiology and risk factors of AVN in a nationwide population-based cohort of IBD patients. METHODS: Patients newly diagnosed with IBD were identified, and sex- and age-matched participants from the general population were selected in a 1:3 IBD:non-IBD ratio. We investigated newly diagnosed AVN and assessed the incidence rates and risk of AVN with multivariate Cox regression models. RESULTS: During the median follow-up period of 7.22±3.85 years, 357 (0.62â¯%) were newly diagnosed with AVN. The risk of AVN was higher in IBD (aHR = 1.42, 95â¯% CI: 1.25-1.62). Ulcerative colitis (UC) patients showed a particularly elevated risk of developing AVN. IBD patients with higher cumulative corticosteroid intake and exposed to a mean prednisolone-equivalent daily dose>20 mg for >1 month were at higher risk of AVN. In Crohn's disease (CD), longer exposure time to >20 mg prednisolone-equivalent presented a trend in increased risk. CONCLUSION: AVN risk was higher in IBD than in those without, particularly in UC and corticosteroid use in IBD could pose a crucial role. These underscore the importance of considering the AVN etiological factors, particularly corticosteroid use.
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STUDY OBJECTIVE: Although the importance of primary percutaneous coronary intervention has been emphasized for ST-segment elevation myocardial infarction (STEMI), the appropriateness of the cardiac catheterization laboratory activation remains suboptimal. This study aimed to develop a precise artificial intelligence (AI) model for the diagnosis of STEMI and accurate cardiac catheterization laboratory activation. METHODS: We used electrocardiography (ECG) waveform data from a prospective percutaneous coronary intervention registry in Korea in this study. Two independent board-certified cardiologists established a criterion standard (STEMI or Not STEMI) for each ECG based on corresponding coronary angiography data. We developed a deep ensemble model by combining 5 convolutional neural networks. In addition, we performed clinical validation based on a symptom-based ECG data set, comparisons with clinical physicians, and external validation. RESULTS: We used 18,697 ECGs for the model development data set, and 1,745 (9.3%) were STEMI. The AI model achieved an accuracy of 92.1%, sensitivity of 95.4%, and specificity of 91.8 %. The performances of the AI model were well balanced and outstanding in the clinical validation, comparison with clinical physicians, and the external validation. CONCLUSION: The deep ensemble AI model showed a well-balanced and outstanding performance. As visualized with gradient-weighted class activation mapping, the AI model has a reasonable explainability. Further studies with prospective validation regarding clinical benefit in a real-world setting should be warranted.
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BACKGROUND: The indications, benefits, and outcomes of percutaneous transluminal renal artery intervention (PTRI) remain controversial. The study purpose was to evaluate the long-term outcomes of PTRI in clinical practice. METHODS: A retrospective review of 217 subjects (254 renal arteries; mean age, 59.8 years) who underwent PTRI based on medical database. RESULTS: The most common cause of renal artery stenosis was atherosclerosis in 217 (85.4%), followed by Takayasu arteritis (TA) in 23 (9.1%), fibromuscular dysplasia in five (2.0%) and others in nine (3.5%). Mean follow-up duration was 5.7 ± 3.7 years. The first restenosis rate was 7.5% (n = 19; highest in TA: n = 9, 47.4%) and second restenosis occurred in six arteries (five TAs, one fibromuscular dysplasia). Follow-up blood pressure improved from 142.0/83.5 to 122.8/73.5 mmHg (P < 0.001). There was no change within 5 years' follow-up in estimated glomerular filtration rate (P = 0.44), whereas TA changed from 69.8 ± 20.5 to 84.2 ± 17.9 mL/min/1.73 m² (P = 0.008). Progressive renal dysfunction was related to diabetes mellitus, chronic kidney disease, and peripheral artery obstructive disease on multivariate analysis with hazard ratios (95% confidence intervals) of 2.24 (1.21-4.17), 2.54 (1.33-4.84), and 3.93 (1.97-7.82), respectively. CONCLUSIONS: PTRI was associated with a blood pressure reduction. Despite a higher rate of restenosis, patients with TA showed significant improvement in estimated glomerular filtration rate. Diabetes mellitus, chronic kidney disease, and peripheral artery obstructive disease were related with progressive renal dysfunction after PTRI.
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The appropriateness of hospitalization for nursing home (NH) residents is still up for debate, with determining factors including timeliness, available treatment, healthcare staff, medication options in hospitals, and safety issues. Although the factors leading to hospitalization have been studied expansively, research on staffing is limited. Thus, this study aimed to investigate organizational predictors, nurse staffing, and government incentives and find important factors to hospitalization due to infection or disease among NH residents in Korea. A cross-sectional design was used, and data were collected via survey from a total of 51 NHs from August 27, 2021 to March 25, 2022. A total of 32 explanatory variables were included. The response variable was the count of hospitalized residents due to infection or disease. We analyzed data using least absolute shrinkage and negative binomial regression. We found that registered nurses' increased hours per resident day were related to decreased hospitalizations due to infection or disease. Appropriate retention and recruitment of nurse staffing with professional leadership should be performed to increase the quality of care for NH residents.