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Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 µg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.
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BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is challenging despite its usefulness. Underwater ESD (UESD) provides better traction and a clearer view of the submucosal layer than conventional ESD (CESD). This study compared the efficiency of UESD and CESD for large (20-50 mm) laterally spreading tumor (LST). METHODS: Preplanned sample size was calculated from our previous experience. As a results, 28 patients were required to UESD group or CESD group, respectively. The primary outcome was total procedure time while the secondary outcome was dissection speed. RESULTS: Fifty-six patients were enrolled and a total of 28 patients were assigned to each group. The mean size of LST was 31.6 mm and 31.3 mm in the UESD and CESD group, respectively. Fibrosis was observed in 67.9% and 60.7% patients in the UESD and CESD group. Total procedure time (mean [SD]) for the UESD group was significantly shorter than that for the CESD group, respectively (49.5 minutes [20.3] vs 75.7 minutes [36.1]; mean difference, -26.2 minutes; 95% CI, -42.0 to -10.5). Dissection speed of the UESD group was significantly faster than that of the CESD group (21.9 mm2/min [6.9] vs 15.2 mm2/min [7.3]; mean difference, 6.7 mm2/minutes; 95% CI, 2.8-10.4). There was no difference between groups in the R0 resection rate or en bloc resection rate. No perforations were observed in either group. CONCLUSIONS: UESD was superior to CESD in total procedure time and dissection speed. UESD can be recommended as the preferred method for the resection of large LST.
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The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.
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Fibrilação Atrial , Embolia , Acidente Vascular Cerebral , Masculino , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Estudos Prospectivos , Átrios do Coração , Embolia/epidemiologia , Embolia/etiologia , Embolia/prevenção & controle , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance. METHODS: This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses. DISCUSSION: This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do .
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapêutico , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Bismuto/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Metronidazol/uso terapêutico , Estudos Multicêntricos como Assunto , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Projetos de PesquisaRESUMO
In the first synapse of the blood-pressure-regulating pathway, a neurokinin (NK) family peptide substance P (SP) is release with an excitatory neurotransmitter, glutamate, to enhance the sensitivity of the baroreflex responses. However, the underlying mechanisms of action are not yet well understood. The effects of NK receptor antagonists and agonists on solitary tract stimulation-evoked excitatory postsynaptic responses were recorded using whole-cell patch-clamp recordings of neurons in the medial portion of the nucleus tractus solitarius (mNTS) in the brainstem. SP reduced the amplitude of the evoked excitatory postsynaptic currents (eEPSCs) and shifted the holding current inward, in a dose-dependent manner. The concentrations of SP needed to induce such responses were different between capsaicin-sensitive unmyelinated (C-type) and capsaicin-resistant myelinated (A-type) neurons. The perfusion of a NK1 receptor antagonist, sendide, reduced the amplitude of eEPSCs in all tested neurons but did not affect the levels of the holding current. A Neurokinin type 1 receptor (NK1 receptor) agonist, [Sar9, Met(O2)11]-SP, reduced the amplitude of the eEPSCs and shifted the holding current inward in capsaicin-resistant neurons; however, it failed to induce any significant changes in the capsaicin-sensitive neurons. Furthermore, a selective Neurokinin type 3 receptor (NK3 receptor) antagonist, SB223412, failed to induce any changes in any tested neuron. In current-clamp experiments, sendide reduced solitary tract (ST)-stimulation evoked firing of action potentials in both A- and C-type neurons. [Sar9, Met(O2)11]-SP suppressed the firing of the action potentials in C-type but not A-type neurons. In spontaneous synaptic recordings, SP reduced frequency of the sEPSCs in CAP sensitive neuron but NK1 agonist reduced at capsaicin resistant neurons. Taken together, the findings show that ST activation leads to the co-transmission of SP and glutamate and enhances baroreflex sensitivity by potentiating the amplitude of eEPSC in an NK1 receptor activity-dependent manner.
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Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.
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This study aimed to investigate the efficacy and safety of human gut-derived multi-strain probiotics in patients with irritable bowel syndrome (IBS). This was an open-label, prospective, observational study. Patients with IBS were administered human gut-derived multi-strain probiotics for 4 weeks. The primary and secondary outcomes were based on the overall responder rate of the total IBS severity scoring system (IBS-SSS) score (>50-point decrease) and the IBS quality of life (IBS-QOL) score and IBS-SSS1 subscore (>10-point decrease in both scores), respectively. The estimated response rate is 55%. Of 44 patients, the total IBS-SSS score responder rate was 18.2% and 63.6% of patients at 2 and 4 weeks, respectively (P = .018). Compared with baseline, a significant improvement in the IBS-QOL score was observed in 27.3% and 63.6% of patients at 2 and 4 weeks, respectively (P = .001). Overall improvement rates in the IBS-SSS1 subscore were observed in 29.5% and 61.4% of patients at 2 and 4 weeks, respectively (P < .001). Primary and secondary outcomes were higher at 4 weeks (total IBS-SSS score, 63.6%; IBS-QOL score, 63.6%; IBS-SSS1 subscore, 61.4%) than the estimated responder rate (55%). Human gut-derived multi-strain probiotics have the potential to become an effective and safe treatment option for IBS patients.
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Síndrome do Intestino Irritável , Probióticos , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Probióticos/uso terapêuticoRESUMO
With its increasing value as a means of public transportation, the health effects of the air in subway stations have attracted public concern. In the current study, we investigated the pulmonary toxicity of dust collected from an air purifier installed on the platform of the busiest subway station in Seoul. We found that the dust contained various elements which are attributable to the facilities and equipment used to operate the subway system. Particularly, iron (Fe), chromium (Cr), zirconium (Zr), barium (Ba), and molybdenum (Mo) levels were more notable in comparison with those in dust collected from the ventilation chamber of a subway station. To explore the health effects of inhaled dust, we first instilled via the trachea in ICR mice for 13 weeks. The total number of pulmonary macrophages increased significantly with the dose, accompanying hematological changes. Dust-laden alveolar macrophages and inflammatory cells accumulated in the perivascular regions in the lungs of the treated mice, and pulmonary levels of CXCL-1, TNF-α, and TGF-ß increased clearly compared with the control. The CCR5 and CD54 level expressed on BAL cell membranes was also enhanced following exposure to dust, whereas the CXCR2 level tended to decrease in the same samples. In addition, we treated the dust to alveolar macrophages (known as dust cells), lysosomal and mitochondrial function decreased, accompanied by cell death, and NO production was rapidly elevated with concentration. Moreover, the expression of autophagy- (p62) and anti-oxidant (SOD-2)-related proteins increased, and the expression of inflammation-related genes was dramatically up-regulated in the dust-treated cells. Therefore, we suggest that dysfunction of alveolar macrophages may importantly contribute to dust-induced inflammatory responses and that the exposure concentrations of Cr, Fe, Mo, Zr, and Ba should be considered carefully when assessing the health risks associated with subway dust. We also hypothesize that the bound elements may contribute to dust-induced macrophage dysfunction by inhibiting viability.
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Pneumonia , Ferrovias , Animais , Camundongos , Camundongos Endogâmicos ICR , Macrófagos Alveolares , Pneumonia/induzido quimicamente , PoeiraRESUMO
Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1ß, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.
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BACKGROUND: It is not clear whether the data regarding rhythm control during atrial fibrillation (AF) contained in AF registries is prognostically significant. Thus, this study investigated the relationship between rhythm control and cardiovascular outcomes in patients in contemporary AF registries. METHODS: This study was conducted using data from 6670 patients with AF receiving oral anticoagulation in the CODE-AF registry. We used propensity overlap weighting to account for differences in baseline characteristics between the rhythm control and rate control groups. The primary outcome was a composite of the rate of death due to cardiovascular causes, stroke, acute coronary syndrome, and heart failure. The secondary outcomes were individual components of the primary outcome. RESULTS: In the CODE-AF registry, 5407 (81.1%) patients were enrolled three months after AF diagnosis. During a median follow-up period of 973 days (interquartile range: 755-1089 days), a primary outcome event occurred in 72 patients in the rhythm control group (1.4 events per 100 person-years) and in 211 patients in the rate control group (1.8 events per 100 person-years). However, after overlap weighting, the incidence rates were 1.4 and 1.5 events per 100 person-years, respectively. No significant difference was found in either the primary outcome (weighted HR: 0.87; 95% CI: 0.66-1.17; p = 0.363) or secondary outcomes between the rhythm control and rate control groups. CONCLUSION: In a prospective AF registry in which most of the population was enrolled at least three months after AF diagnosis, no difference in the risk of cardiovascular or cerebrovascular outcomes was found between the rhythm control and rate control groups, suggesting the early rhythm control should be considered to improve the outcome of patients.
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Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic issue. In addition to the well-known respiratory and fever symptoms, gastrointestinal symptoms have also been reported. This study aimed to evaluate the prevalence and prognosis of patients with COVID-19 infection complicated with acute pancreatitis in intensive care unit (ICU). METHODS: This was a retrospective observational cohort study, and patients aged 18 years or older, admitted into the ICU in a single tertiary center from January 1, 2020, to April 30, 2022 were enrolled. Patients were identified by electronic medical records and reviewed manually. The primary outcome was the prevalence of acute pancreatitis among ICU patients with COVID-19. The secondary outcomes were the length of hospital stay, need for mechanical ventilation (MV), need for continuous renal replacement therapy (CRRT), and in-hospital mortality. RESULTS: A total of 4133 patients, admitted into the ICU, were screened. Among these patients, 389 were infected by COVID-19, and 86 were diagnosed with acute pancreatitis. COVID-19 positive patients were more likely to present with acute pancreatitis than COVID-19 negative patients (odds ratio = 5.42, 95% confidence interval: 2.35-6.58, P < 0.01). However, the length of hospital stay, need for MV, need for CRRT, and in-hospital mortality were not significantly different between acute pancreatitis patients with and without COVID-19 infection. CONCLUSIONS: Severe COVID-19 infections may cause acute pancreas damage in critically ill patients. However, the prognosis may not differ between acute pancreatitis patients with and without COVID-19 infection.
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COVID-19 , Pancreatite , Humanos , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos de Coortes , Estado Terminal/terapia , Prevalência , Doença Aguda , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/terapia , Prognóstico , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
Background: Ablation-based treatment has emerged as an alternative rhythm control strategy for symptomatic atrial fibrillation (AF). Recent studies have demonstrated the cost-effectiveness of ablation compared with medical therapy in various circumstances. We assessed the economic comparison between ablation and medical therapy based on a nationwide real-world population. Methods and findings: For 192,345 patients with new-onset AF (age ≥ 18 years) identified between August 2015 and July 2018 from the Korean Health Insurance Review and Assessment Service (HIRA) database, medical resource use data were collected to compare AF patients that underwent ablation (N = 2,131) and those administered antiarrhythmic drugs (N = 8,048). Subsequently, a Markov chain Monte Carlo model was built. The patients had at least one risk factor for stroke, and the base-case used a 20-year time horizon, discounting at 4.5% annually. Transition probabilities and costs were estimated using the present data, and utilities were derived from literature review. The costs were converted to US $ (2019). Sensitivity analyses were performed using probabilistic and deterministic methods. The net costs and quality-adjusted life years (QALY) for antiarrhythmic drugs and ablation treatments were $37,421 and 8.8 QALYs and $39,820 and 9.3 QALYs, respectively. Compared with antiarrhythmic drugs, incremental cost-effectiveness ratio of ablation was $4,739/QALY, which is lower than the willingness-to-pay (WTP) threshold of $32,000/QALY. Conclusion: In symptomatic AF patients with a stroke risk under the age of 75 years, ablation-based rhythm control is potentially a more economically attractive option compared with antiarrhythmic drug-based rhythm control in Korea.
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PURPOSE: Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. MATERIALS AND METHODS: Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m²) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. RESULTS: During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). CONCLUSION: Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC. ClinicalTrials.gov (NCT02786095).
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Fibrilação Atrial , Embolia , Falência Renal Crônica , Infarto do Miocárdio , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Varfarina/uso terapêutico , Anticoagulantes/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Embolia/prevenção & controle , Embolia/tratamento farmacológico , Embolia/epidemiologia , Infarto do Miocárdio/complicações , Sistema de Registros , Administração OralRESUMO
PURPOSE: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0-1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m²), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0-1. MATERIALS AND METHODS: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0-1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. RESULTS: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P-Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11-0.63, p=0.003). CONCLUSION: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0-1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0-1.
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Fibrilação Atrial , Acidente Vascular Cerebral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Biomarcadores , Estudos de Coortes , Creatinina , Feminino , Fibrinolíticos , Humanos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
Background Atrial fibrillation (AF) is associated with an increased risk of poor cardiovascular outcomes; appropriate rhythm control can reduce the incidence of these adverse events. Therefore, catheter ablation is recommended in symptomatic patients with AF. The aims of this study were to compare AF-related outcomes according to a baseline symptom scale score and to determine the best treatment strategy for asymptomatic patients with AF. Methods and Results This study enrolled all patients who completed a baseline Atrial Fibrillation Effect on Quality-of-Life (AFEQT) survey in a prospective observational registry. The patients were divided into 2 groups according to AFEQT score at baseline; scores ≤80 were defined as symptomatic, whereas scores >80 represented asymptomatic patients. The primary outcome was defined as a composite of hospitalization for heart failure, ischemic stroke, or cardiac death. This study included 1515 patients (mean age: 65.7±10.5 years; 998 [65.9%] men). The survival curve showed a poorer outcome in the symptomatic group compared with the asymptomatic group (log-rank P=0.04). Rhythm control led to a significantly lower risk of a composite outcome in asymptomatic patients (hazard ratio [HR], 0.47 [95% CI, 0.27-0.84], P=0.01). Rhythm control was associated with more favorable composite outcomes in the asymptomatic group with paroxysmal AF, left atrium diameter ≤50 mm, and CHA2DS2-VASc score ≥3. Conclusions Symptomatic patients with AF experienced more adverse outcomes compared with asymptomatic patients. In asymptomatic patients with AF, a strategy of rhythm control improved the outcomes, especially with paroxysmal AF, smaller left atrium size, or higher stroke risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02786095.
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Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. METHODS: This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA2DS2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. RESULTS: Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25th and 75th percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25-0.91, p=0.025) than men. CONCLUSIONS: In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02786095.
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Background: Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data. Methods: We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained. Results: The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis. Conclusion: Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.
RESUMO
Background: Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively). Methods: Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61-80 bpm, 81-110 bpm, and >110 bpm. Results: A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61-80 bpm group: hazard ratio, 0.66; 95% CI, 0.46-0.94; p = 0.021; 81-110 bpm group: hazard ratio, 0.60; 95% CI, 0.40-0.90; p = 0.013). Especially, HFpEF patients with HR 81-110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011). Conclusion: In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.