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BACKGROUND: In recent years, alternative monitoring approaches, such as risk-based and remote monitoring techniques, have been recommended instead of traditional on-site monitoring to achieve more efficient monitoring. Remote risk-based monitoring (R2BM) is a monitoring technique that combines risk-based and remote monitoring and focuses on the detection of critical data and process errors. Direct data capture (DDC), which directly collects electronic source data, can facilitate R2BM by minimizing the extent of source documents that must be reviewed and reducing the additional workload on R2BM. In this study, we evaluated the effectiveness of R2BM and the synergistic effect of combining R2BM with DDC. METHODS: R2BM was prospectively conducted with eight participants in a randomized clinical trial using a remote monitoring system that uploaded photographs of source documents to a cloud location. Critical data and processes were verified by R2BM, and later, all were confirmed by on-site monitoring to evaluate the ability of R2BM to detect critical data and process errors and the workload of uploading photographs for clinical trial staff. In addition, the reduction of the number of uploaded photographs was evaluated by assuming that the DDC was introduced for data collection. RESULTS: Of the 4645 data points, 20.9% (n = 973, 95% confidence interval = 19.8-22.2) were identified as critical. All critical data errors corresponding to 5.4% (n = 53/973, 95% confidence interval = 4.1-7.1) of the critical data and critical process errors were detectable by R2BM. The mean number of uploaded photographs and the mean time to upload them per visit per participant were 34.4 ± 11.9 and 26.5 ± 11.8 min (mean ± standard deviation), respectively. When assuming that DDC was introduced for data collection, 45.0% (95% confidence interval = 42.2-47.9) of uploaded photographs for R2BM were reduced. CONCLUSIONS: R2BM can detect 100% of the critical data and process errors without on-site monitoring. Combining R2BM with DDC reduces the workload of R2BM and further improves its efficiency.
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Fotografação , Humanos , Estudos Prospectivos , Medição de Risco , Carga de Trabalho , Computação em Nuvem , Coleta de Dados/métodos , Feminino , Masculino , Confiabilidade dos Dados , Projetos de PesquisaRESUMO
Background: Clinical data management (CDM) collects, integrates, and makes data available. It plays a vital role in clinical research. However, there are few opportunities for Japanese clinical data managers to learn about its systematic framework, particularly in academic research organizations. While Japanese-language CDM training exists, its effectiveness in a Japanese context requires clarification. Objectives: We aimed to develop an advanced program of instruction for professionals to understand CDM and to determine the effectiveness of the training program. Methods and results: We developed an advanced program including risk-based monitoring and the Clinical Data Interchange Standards Consortium on a trial basis for clinical data managers to provide them with a comprehensive understanding of CDM. Fifty-two people attended the program and reported that they were highly satisfied with it. Conclusions: To provide comprehensive CDM training in Japan, it is imperative to continue improving the content and develop an advanced program. Due to the recent tightening of clinical research regulations and the development and dissemination of various systems for conducting clinical research, the competency-based educational program requires further development.
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AIMS: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation. We aim to evaluate the safety, pharmacokinetics and pharmacodynamics of TMS-007 in healthy volunteers. METHODS: This was a randomized, placebo-controlled, double blind, dose-escalation study, administered as a single intravenous infusion of TMS-007 in cohorts of healthy male Japanese subjects. Six cohorts were planned, but only five were completed. In each cohort (n = 8), individuals were randomized to receive one of five doses of TMS-007 (3, 15, 60, 180 or 360 mg; n = 6) or placebo (n = 2). RESULTS: TMS-007 was generally well tolerated, and no serious adverse events were attributed to the drug. A linear dose-dependency was observed for plasma TMS-007 levels. No symptoms of bleeding were observed on brain MRI analysis, and no bleeding-related responses were found on laboratory testing. The plasma levels of the coagulation factor fibrinogen and the anti-fibrinolysis factor α2 -antiplasmin levels were unchanged after TMS-007 dosing. A slight increase in the plasma level of plasmin-α2 -antiplasmin complex, an index of plasmin formation, was observed in the TMS-007 group in cohort 2. CONCLUSIONS: TMS-007 is generally well tolerated and exhibits favourable pharmacokinetic profiles that warrant further clinical development.
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Antifibrinolíticos , Fibrinolisina , Humanos , Masculino , Fenol , Fenóis/farmacologia , Plasminogênio , Hemorragia/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Método Duplo-Cego , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND/AIM: For patients with T1a muscularis mucosae (MM) esophageal squamous cell carcinoma (ESCC) with lymphovascular invasion (LVI) or T1b submucosal (SM) ESCC, endoscopic resection is non-curative, and adjuvant treatment entailing esophagectomy or definitive chemoradiotherapy is necessary. This is because about 30% of these cases have lymph node (LN) metastasis. The purpose of this study was to test the utility of a CRP genetic polymorphism test kit for determining the risk of LN metastasis with the aim of eliminating additional invasive adjuvant therapy. PATIENTS AND METHODS: This is a retrospective, multi-institutional, observational study. The CRP 1846C>T genetic polymorphisms were identified using a fully automated genotyping system. The primary end points were an 85% negative predictive value (NPV) for diagnosis of LN metastasis in pT1a (MM) and 80% NPV in pT1b (SM1) patients. RESULTS: A total of 742 ESCC (105 pMM, 166 pSM1 and 471 pSM2-3) patients who had received esophagectomy with 2- or 3-field LN dissection at 65 institutions were enrolled. According to this test, patients with the C/C and C/T genotypes were considered to be low risk. The NPVs using this test were 82.8% in pMM and 71.7% in pSM1 patients. CONCLUSION: CRP 1846C>T genetic polymorphism is not a useful diagnostic indicator for determining the risk of LN metastasis; however, the possibility that CRP gene polymorphisms are involved in the mechanism of lymph node metastasis in solid tumors still remains.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Metástase Linfática , Estudos Retrospectivos , Neoplasias Esofágicas/genética , Polimorfismo Genético/genética , Adjuvantes ImunológicosRESUMO
BACKGROUND: The effect of treatment with paclitaxel-containing devices (PTXD) on mortality in patients with peripheral artery disease remains controversial.MethodsâandâResults:An independent patient-level meta-analysis of 12 clinical trials (1,389 PTXD patients and 1,192 non-PTXD patients) was conducted. This study included 7 pivotal trials and 5 post-marketing surveillance studies on endovascular treatment for femoropopliteal artery by 6 companies. The primary endpoint was all-cause death, and 5-year cumulative mortality was estimated by a Kaplan-Meier curve. Cox proportional hazard model was used to calculate the hazard ratio (HR) and confidential interval (CI). During the median follow up of 3.0 years, 459 patients died. The cumulative 5-year mortality for the entire cohort was significantly lower in the PTXD than in the non-PTXD group (24.4% vs. 27.4%, respectively; HR, 0.81; 95% CI, 0.67-0.97; P=0.023), but this difference was no longer significant after adjustment for relevant covariates (HR, 1.01; 95% CI, 0.39-2.58; P=0.987). The Cox proportional hazard model revealed that sex, hyperlipidemia, Type 2 diabetes, hemodialysis, Rutherford category, and age above 75 years were significantly associated with 5-year mortality, but treatment with PTXD was not. CONCLUSIONS: This large individual meta-analysis of patients with femoropopliteal artery disease found that the use of PTXD does not have a negative effect on 5-year mortality.
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Angioplastia com Balão , Diabetes Mellitus Tipo 2 , Doença Arterial Periférica , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Artéria Femoral , Humanos , Japão/epidemiologia , Paclitaxel , Doença Arterial Periférica/terapia , Artéria Poplítea , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
BACKGROUND/AIMS: Traditional on-site monitoring of clinical trials via frequent site visits and 100% source data verification is cost-consuming, and it still cannot guarantee data quality effectively. Depending on the types and designs of clinical trials, an alternative would be combining several monitoring methods, such as risk-based monitoring and remote monitoring. However, there is insufficient evidence of its effectiveness. This research compared the effectiveness of risk-based monitoring with a remote monitoring system with that of traditional on-site monitoring. METHODS: With a cloud-based remote monitoring system called beagle View®, we created a remote risk-based monitoring methodology that focused only on critical data and processes. We selected a randomized controlled trial conducted at Tohoku University Hospital and randomly sampled 11 subjects whose case report forms had already been reviewed by data managers. Critical data and processes were verified retrospectively by remote risk-based monitoring; later, all data and processes were confirmed by on-site monitoring. We compared the ability of remote risk-based monitoring to detect critical data and process errors with that of on-site monitoring with 100% source data verification, including an examination of clinical trial staff workload and potential cost savings. RESULTS: Of the total data points (n = 5617), 19.7% (n = 1105, 95% confidence interval = 18.7-20.7) were identified as critical. The error rates of critical data detected by on-site monitoring, remote risk-based monitoring, and data review by data managers were 7.6% (n = 84, 95% CI = 6.2-9.3), 7.6% (n = 84, 95% confidence interval = 6.2-9.3), and 3.9% (n = 43, 95% confidence interval = 2.9-5.2), respectively. The total number of critical process errors detected by on-site monitoring was 14. Of these 14, 92.9% (n = 13, 95% confidence interval = 68.5-98.7) and 42.9% (n = 6, 95% confidence interval = 21.4-67.4) of critical process errors were detected by remote risk-based monitoring and data review by data managers, respectively. The mean time clinical trial staff spent dealing with remote risk-based monitoring was 9.9 ± 5.3 (mean ± SD) min per visit per subject. Our calculations show that remote risk-based monitoring saved between 9 and 41 on-site monitoring visits, corresponding to a cost of between US$13,500 and US$61,500 per trial site. CONCLUSION: Remote risk-based monitoring was able to detect critical data and process errors as well as on-site monitoring with 100% source data verification, saving travel time and monitoring costs. Remote risk-based monitoring offers an effective alternative to traditional on-site monitoring of clinical trials.
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Confiabilidade dos Dados , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: We performed a large, multicenter, randomized controlled trial to determine the efficacy and safety of early colonoscopy on outcomes of patients with acute lower gastrointestinal bleeding (ALGIB). METHODS: We performed an open-label study at 15 hospitals in Japan of 170 patients with ALGIB randomly assigned (1:1) to groups that underwent early colonoscopy (within 24 hours of initial visit to the hospital) or elective colonoscopy (24-96 hours after hospital admission). The primary outcome was identification of stigmata of recent hemorrhage (SRH). Secondary outcomes were rebleeding within 30 days, endoscopic treatment success, need for transfusion, length of stay, thrombotic events within 30 days, death within 30 days, and adverse events. RESULTS: SRH were identified in 17 of 79 patients (21.5%) in the early colonoscopy group vs 17 of 80 patients (21.3%) in the elective colonoscopy group (difference, 0.3; 95% confidence interval, -12.5 to 13.0; P = .967). Rebleeding within 30 days of hospital admission occurred in 15.3% of patients in the early colonoscopy group and 6.7% of patients in the elective colonoscopy group (difference, 8.6; 95% confidence interval, -1.4 to 18.7); there were no significant differences between groups in successful endoscopic treatment rate, transfusion rate, length of stay, thrombotic events, or death within 30 days. The adverse event of hemorrhagic shock occurred during bowel preparation in no patient in the early group vs 2 patients (2.5%) in the elective colonoscopy group. CONCLUSIONS: In a randomized controlled study, we found that colonoscopy within 24 hours after hospital admission did not increase SRH or reduce rebleeding compared with colonoscopy at 24-96 hours in patients with ALGIB. ClinicalTrials.gov, Numbers: UMIN000021129 and NCT03098173.
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Doenças do Colo/cirurgia , Colonoscopia/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hemorragia Gastrointestinal/cirurgia , Tempo para o Tratamento , Doença Aguda/mortalidade , Doença Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/estatística & dados numéricos , Doenças do Colo/mortalidade , Feminino , Hemorragia Gastrointestinal/mortalidade , Mortalidade Hospitalar , Humanos , Japão , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
The original article can be found online.
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BACKGROUND: The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. METHODS: This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. DISCUSSION: This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. TRIAL REGISTRATION: UMIN-CTR Identifier, UMIN000021129 . Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173 . Registered on 24 March 2017.
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Assistência Ambulatorial/métodos , Colonoscopia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Hemostase Endoscópica/métodos , Diagnóstico Precoce , Estudos de Equivalência como Asunto , Hemorragia Gastrointestinal/etiologia , Hemostase Endoscópica/efeitos adversos , Humanos , Japão , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. METHODS: We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. RESULTS: The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.I1157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. CONCLUSIONS: The common occurrence of genotype C3, especially the p.I1157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.I1157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.
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Síndrome Hemolítico-Urêmica Atípica/genética , Patrimônio Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Proteínas do Sistema Complemento , Feminino , Humanos , Lactente , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. METHODS AND RESULTS: We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT®) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy. The primary endpoints were changes from baseline in serum albumin and cardiothoracic ratio (CTR). Sixteen patients completed the study. The mean (± standard deviation) period of BCAA supplementation was 18.4 ± 8.4 days. Serum albumin significantly increased in the BCAA group [mean difference vs baseline, 0.44 g/dL; 95% confidence interval (CI) 0.13-0.76; P = 0.014] and did not change in controls (0.18 g/dL; 95% CI - 0.05 to 0.40; P = 0.108). CTR significantly decreased in the BCAA group (- 2.3%; 95% CI - 3.8 to - 0.8; P = 0.014) and did not change in controls (- 1.0%; 95% CI - 2.3 to 0.3; P = 0.111). CONCLUSION: In-hospital HF patients with hypoalbuminemia supplemented with BCAAs showed increased serum albumin and decreased CTR. Clinical trial registration number UMIN000004488 [ http://www.umin.ac.jp/ctr/index.htm ].
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Aminoácidos de Cadeia Ramificada/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Hipoalbuminemia/sangue , Albumina Sérica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. METHODS: This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. DISCUSSION: In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. TRIAL REGISTRATION: This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).
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Aminoácidos de Cadeia Ramificada/administração & dosagem , Caquexia/tratamento farmacológico , Reabilitação Cardíaca , Insuficiência Cardíaca/reabilitação , Músculo Esquelético/efeitos dos fármacos , Sarcopenia/tratamento farmacológico , Disfunção Ventricular Esquerda/reabilitação , Aminoácidos de Cadeia Ramificada/efeitos adversos , Caquexia/complicações , Caquexia/diagnóstico , Caquexia/fisiopatologia , Reabilitação Cardíaca/efeitos adversos , Doença Crônica , Protocolos Clínicos , Diástole , Metabolismo Energético/efeitos dos fármacos , Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão , Força Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Recuperação de Função Fisiológica , Projetos de Pesquisa , Sarcopenia/complicações , Sarcopenia/diagnóstico , Sarcopenia/fisiopatologia , Sístole , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
PURPOSE: The aim of this study is to investigate the relationship between arterial pulse amplitude change under increased shear stress and the presence of ischemic heart disease (IHD). METHODS: This study comprised 31 subjects, including 14 subjects with IHD. We investigated the change in brachial artery pulse amplitude during flow-mediated dilation (FMD) using ultrasonography. RESULTS: The arterial pulse amplitude increased during FMD in 19 subjects, whereas it decreased in 12 subjects. There was a marked difference in the change in arterial pulse amplitude (the maximum amplitude of the arterial pulse amplitude during FMD/the arterial pulse amplitude at baseline) between subjects with and without IHD (0.98 ± 0.53 and 1.37 ± 0.53, p = 0.028). Furthermore, decreased arterial pulse amplitude during FMD was a significant predictor of IHD after adjustment of age, blood pressure, the presence of each type of coronary risks, the value of FMD and sex (p = 0.0001). CONCLUSIONS: The decrease of arterial pulsation amplitude during FMD was a useful predictive parameter for IHD.
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The clinical meaning of changes in PP with posture remains unclear. We performed treadmill exercise testing on 144 subjects to diagnose ischemic heart disease, and measured the PPs in the supine and standing positions. The differences in the two PPs ranged between -35 and 45 mmHg. Eleven subjects were diagnosed with significant coronary ischemia. The differences in the PPs were significantly increased, and PP in the standing position was significantly elevated in these subjects. A large difference in the PPs in the standing and supine positions was associated with significant coronary ischemia, independent of significant covariables.
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Pressão Sanguínea/fisiologia , Isquemia Miocárdica , Intolerância Ortostática , Idoso , Teste de Esforço/métodos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Intolerância Ortostática/diagnóstico , Intolerância Ortostática/etiologia , Intolerância Ortostática/fisiopatologia , Postura/fisiologia , Decúbito Dorsal/fisiologiaRESUMO
The clinical meaning of changes in PP with posture remains unclear. We performed treadmill exercise testing on 144 subjects to diagnose ischemic heart disease, and measured the PPs in the supine and standing positions. The differences in the two PPs ranged between -35 and 45 mmHg. Eleven subjects were diagnosed with significant coronary ischemia. The differences in the PPs were significantly increased, and PP in the standing position was significantly elevated in these subjects. A large difference in the PPs in the standing and supine positions was associated with significant coronary ischemia, independent of significant covariables.
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Aortic stenosis (AS) is the most common valvular disease and aortic valve replacement (AVR) is one of its most effective interventions. AS affects not only the left ventricle, but also vascular function beyond the stenotic valve, which can lead to various types of vascular dysfunction. However, research evaluating the effect of AS on aortic vascular function is limited. In this study, we investigated clinical meaning to evaluate endothelial function in subjects with AS. From April 2011 to April 2012, 20 consecutive adult patients with degenerative AS (mean age, 74.7 ± 7.4 years; range 50-83 years) who underwent AVR at our institution were included in the study. We measured flow-mediated dilation (FMD) to evaluate the effect of AS on endothelial function. The difference between brachial artery diameter (BAD) before (4.0 ± 0.7 mm) and after AVR (3.9 ± 0.6 mm) was not significant (p = 0.043), but FMD significantly improved after AVR (from 3.1 ± 1.8 to 6.0 ± 2.7 %, p < 0.0001). We also analyzed FMD × BAD index, endogenous vasodilatory capability independent of BAD, resulting that it also significantly increased after AVR (12.3 ± 7.0-22.5 ± 9.3, p < 0.0001). We divided patients into two groups by pre- to post-AVR change in FMD (ΔFMD); large-ΔFMD group [ΔFMD >3.0 % (median value)] and small-ΔFMD group (ΔFMD <3.0 %). There were no significant changes in age, blood pressure, heart rate, B-type natriuretic peptide, or echocardiographic parameters in either group. In contrast, BAD was significantly larger in the small ΔFMD group (4.3 ± 0.7 mm) than in the large ΔFMD group (3.7 ± 0.7 mm) (p = 0.030). In addition, cardio-thoracic ratio was significantly greater in the small ΔFMD group (58.4 ± 7.1 %) than in the large ΔFMD group (53.7 ± 4.6 %) (p = 0.048). Receiver operating characteristic curve analysis of BAD to differentiate large and small ΔFMD demonstrated an area under the curve of 0.750 (p = 0.059) and that optimal cutoff for BAD was 4.28 mm (70 % sensitivity, 80 % specificity). AVR in subjects with AS is associated with a significant improvement in FMD in the brachial artery. Measurement of the BAD may be helpful in distinguishing whether the impairment of FMD in AS derives from a stenotic valve or vascular remodeling.
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Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Implante de Prótese de Valva Cardíaca , Vasodilatação , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Área Sob a Curva , Artéria Braquial/diagnóstico por imagem , Ecocardiografia Doppler de Pulso , Endotélio Vascular/diagnóstico por imagem , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Resultado do TratamentoRESUMO
PURPOSE: The physiological role of vasomotion, rhythmic oscillations in vascular tone or diameter, and its underlying mechanisms are unknown. We investigated the characteristics of brachial artery vasomotion in patients with ischemic heart disease (IHD). METHODS: We performed a retrospective study of 37 patients with IHD. Endothelial function was assessed using flow-mediated dilation (FMD), and power spectral analysis of brachial artery diameter oscillations during FMD was performed. Frequency-domain components were calculated by integrating the power spectrums in three frequency bands (in ms2) using the MemCalc (GMS, Tokyo, Japan): very-low frequency (VLF), 0.003-0.04 Hz; low frequency (LF), 0.04-0.15 Hz; and high frequency (HF), 0.15-0.4 Hz. Total spectral power (TP) was calculated as the sum of all frequency bands, and each spectral component was normalized against TP. RESULTS: Data revealed that HF/TP closely correlated with FMD (râ=â-0.33, pâ=â0.04), whereas VLF/TP and LF/TP did not. We also explored the relationship between elevated C-reactive protein (CRP) levels and vasomotion. HF/TP was significantly increased in subjects with high CRP levels (CRP;>0.08 mg/dL) compared with subjects with low CRP levels (0.052±0.026 versus 0.035±0.022, p<0.05). The HF/TP value closely correlated with CRP (râ=â0.24, pâ=â0.04), whereas the value of FMD did not (râ=â0.023, pâ=â0.84). In addition, elevated CRP levels significantly increased the value of HF/TP after adjustment for FMD and blood pressure (ßâ=â0.33, p<0.05). CONCLUSION: The HF component of brachial artery diameter oscillation during FMD measurement correlated well with FMD and increased in the presence of elevated CRP levels in subjects with IHD.
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Artéria Braquial/fisiopatologia , Proteína C-Reativa/metabolismo , Isquemia Miocárdica/sangue , Sistema Vasomotor/metabolismo , Idoso , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea , Artéria Braquial/metabolismo , Eletrocardiografia , Feminino , Frequência Cardíaca , Hemoglobinas/metabolismo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Tóquio , Sistema Vasomotor/fisiopatologiaRESUMO
The aim of this study was to evaluate the add-on effect of aliskiren to valsartan on endothelial-dependent vasodilation in hypertensive patients with ischemic heart disease (IHD). After 4 weeks of treatment with 80 mg of valsartan, 28 patients were allocated to either continued treatment with valsartan or an add-on treatment with valsartan plus 150 mg of aliskiren. Aliskiren significantly decreased plasma renin activity, whereas endothelium-dependent vasodilation measured by flow-mediated dilation (FMD) did not change. In contrast, heart rate significantly decreased (73.1 ± 9.8 to 66.3 ± 7.0 beats per minute at baseline and 24 weeks, respectively [P = .009]) and the standard deviation of the R-R intervals (SDNN) significantly increased in the aliskiren group. The add-on aliskiren to valsartan therapy may not improve endothelial functions, although it significantly reduced resting heart rate via regulation of the autonomic nervous system in hypertensive patients with IHD.
Assuntos
Amidas/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Anti-Hipertensivos/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Fumaratos/farmacologia , Hipertensão/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Tetrazóis/farmacologia , Valina/análogos & derivados , Idoso , Amidas/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Sistema Nervoso Autônomo/fisiologia , Comorbidade , Quimioterapia Combinada , Endotélio Vascular/fisiologia , Feminino , Fumaratos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/epidemiologia , Renina/antagonistas & inibidores , Renina/metabolismo , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valina/farmacologia , Valina/uso terapêutico , Valsartana , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
We conducted a retrospective study of 60 patients with ischemic heart disease (31 with diabetes and 29 without diabetes) to investigate the impact of diabetes on diurnal body temperature patterns. We found that the increase of axillary body temperature in the evening was reduced in the presence of diabetes, which was associated with autonomic neuropathy.