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Background: Device-related thrombosis (DRT) after successful closure implantation on left atrial appendage (LAA) was considered as a major challenge and optimal strategy on antithrombotic therapy remains to be solved. This study was performed to compare the clinical effectiveness and safety of reduced rivaroxaban dose (RRD) and dual antiplatelet therapy (DAPT) after left atrial appendage closure (LAAC) implantation with the Watchman device. Methods: After successful LAAC, consecutive participants were medicated with a standard DAPT or RRD. The primary endpoints included DRT, thrombosis events (TE), and bleeding events that were documented during a 12-month follow-up period. Results: 767 patients (DAPT: n = 140; RRD: n = 627) were initially included. After propensity score matching (PSM), 140 patients treated with DAPT and 280 patients with RRD were included in each group with similar baseline information, thromboembolic and bleeding risk factors, cardiovascular risk factors and concomitant medication. In the RRD group, 193 patients were on rivaroxaban 15 mg ( R 15 ) and 47 received rivaroxaban 10 mg ( R 10 ). The incidence of DRT was documented in 12 (9.3%) patients in the DAPT group and 3 (6.3%) in R 10 and 7 (3.0%) in R 15 (log-rank p = 0.050). DAPT subgroups were more likely to experience shorter time to DRT as compared to R 15 ( R 15 vs. DAPT hazard ratio (HR) = 0.334, p = 0.015, 95% CI: 0.131-0.850). The median length of DRT in the R 15 group was significantly lower than that of the DAPT group (1.721 [1.610-1.818] mm vs. 1.820 [1.725-1.925] mm, p = 0.029). Compared with the unadjusted estimated rates of ischemic events for patients with similar congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category ( CHA 2 DS 2 - VAS c ) scores, a significant decrease of 68.6% in ischemic stroke rates was noted in the R 15 group, which contributed to a 54.9% reduction of overall thromboembolic events. The overall minor bleeding was not significantly different amongst the three groups (p = 0.944). Procedural bleeding was more common in the DAPT group, as compared with the R 10 and R 15 groups. Conclusions: After successful closure implantation, long-term RRD significantly reduced the DRT and TE occurrence compared with DAPT.
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BACKGROUND: Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase exposure to rivaroxaban. However, the clinical relevance of this drug-drug interaction is still not clear. OBJECTIVE: The aim was to investigate the risk of bleeding in patients receiving a combination of rivaroxaban and amiodarone. METHODS: This was a prospective observational study in which we included atrial fibrillation patients treated with rivaroxaban. The patients were divided into the rivaroxaban group and the combination of rivaroxaban and amiodarone group (the combination group). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust between-group differences. The primary endpoint was defined as the time to the first occurrence of a composite of major, clinically relevant nonmajor, and minor bleeding. RESULTS: In total, 481 atrial fibrillation patients were included in the analysis. After PSM, 154 patients in the rivaroxaban group were matched with 154 patients in the combination group. The bleeding events mainly consisted of clinically relevant nonmajor and minor bleeding. Only one patient experienced major bleeding. The primary outcome was recorded in 26.0% of patients in the combination group and 10.4% of patients in the rivaroxaban group (hazard ratio = 2.76, 95% CI = 1.55-4.93, P < 0.001). The bleeding risk was significantly higher in the combination group compared with that in the rivaroxaban group in the IPTW and stabilized IPTW analyses (hazard ratio = 2.17, 95% CI = 1.32-3.56, P = 0.002). CONCLUSION AND RELEVANCE: The combination of rivaroxaban and amiodarone increased the risk of bleeding in patients with atrial fibrillation, especially clinically relevant nonmajor and minor bleeding. Physicians prescribing rivaroxaban and amiodarone together should be concerned about an increase in the risk of nonmajor bleeding.
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PURPOSE: This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects. METHOD: A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (Ctrough) of rivaroxaban, coagulation indicators at the Ctrough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes. RESULTS: Patients with mutant genotype CYP3A4 (rs2242480, rs2246709, and rs3735451) and CYP3A5 (rs776746) had higher levels of rivaroxaban Ctrough, PT values than that of wild-type. Furthermore, a positive relationship was revealed between Ctrough and PT (r = 0.212, p = 0.007), while no significant correlation was found between Ctrough and APTT. Regarding the clinical outcomes, the minor allele carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were associated with higher incidence of minor bleeding (p = 0.028 and p = 0.038, respectively) and were identified as the independent risk factors of minor bleeding treated with rivaroxaban (p = 0.024 and p = 0.036, respectively), with the receiver operating characteristic (ROC) curve validated (AUC = 0.8956, 95% CI: 0.829-0.962). CONCLUSION: The CYP3A4 polymorphisms (rs2242480, rs2246709, and rs3735451) and CYP3A5 rs776746 were associated with variations in rivaroxaban PK/PD. The minor allele (C) carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were correlated with clinical outcomes.
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SUBJECT: To investigate the correlation between mean platelet volume (MPV) levels and Gensini scores in stable coronary heart disease (CHD) patients with or without diabetes. METHODS: A retrospective analysis was conducted on 2525 patients with stable CHD in Zhongshan Hospital, Fudan University. There were 1274 in the low MPV group and 1251 in the high MPV group, divided by a median MPV level of 10.9 fL. In the total population, 1605 patients were non-diabetic and 920 were diabetic. The severity of coronary artery disease was quantified using the Gensini score. RESULTS: The Gensini score was significantly higher in the high MPV group than in the low MPV group (p < 0.001). MPV levels increased significantly with the number of stenotic (>50%) coronary vessels (p < 0.001). The Spearman analysis showed a positive correlation between MPV and Gensini score (r = 0.189, p < 0.001), which was more significant in the diabetic subgroup (r = 0.232, p < 0.001). Receiver operating characteristic (ROC) curves were employed to assess the predictive value of MPV for high Gensini scores, using the median value of 32 points as the cutoff. MPV levels in the diabetes cohort exhibited a higher predictive value for high Gensini scores (area under the curve: 0.635 [0.614-0.657], p < 0.001). Multivariate linear regression analysis showed that diabetes and MPV were independently associated with Gensini scores. CONCLUSION: MPV levels in stable CHD patients can predict the severity of coronary artery stenosis. This correlation is more significant in the presence of diabetes.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Humanos , Volúmen Plaquetario Medio , Estudios Retrospectivos , Diabetes Mellitus/diagnóstico , Enfermedad de la Arteria Coronaria/diagnósticoRESUMEN
BACKGROUND: There have been no reports of tigecycline-associated drug-related liver injury (DILI) identified by histopathological assistance and causal assessment method. We reported the histopathological manifestations for the first time and described tigecycline-associated liver injury's pattern, severity, duration, and outcome. CASE PRESENTATION: A 68-year-old male with post-liver transplantation was given high-dose tigecycline intravenously (loading dose 200 mg, followed by 100 mg every 12 h) combined with polymyxin B (50,000 units by aerosol inhalation every 12 h) for hospital-acquired pneumonia caused by carbapenem-resistant Klebsiella pneumoniae. At the same time, tacrolimus was discontinued. Liver function was initially normal but started to decline on day 4 of tigecycline. Reducing the dose of tigecycline and resuming tacrolimus could not reverse the deterioration. Therefore, a liver puncture biopsy was performed for further diagnosis, with histopathological findings being cytotoxic injury. The updated RUCAM scale was used to evaluate the causal relationship between tigecycline and liver injury, with the result of 7 points indicating a "probable" causality grading. Methylprednisolone was initiated to treat DILI that was determined to be Grade 1 cholestatic injury. Total bilirubin and transaminase levels returned to normal on day 4 and 11 after tigecycline withdrawal, respectively. Monthly outpatient follow-up showed that the patient's liver function stayed normal. CONCLUSIONS: This case possessed a significant reference value for differential diagnosis and treatment prognosis of tigecycline-associated DILI. With early diagnosis and timely management, the tigecycline-associated DILI of this patient was successfully reversed.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Anciano , Causalidad , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Humanos , Klebsiella pneumoniae , Masculino , Tigeciclina/efectos adversosRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF. METHODS: This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val-related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3-12 months, were collected. RESULTS AND DISCUSSION: A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N-terminal pro B-type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3-12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001). WHAT IS NEW AND CONCLUSION: Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val.
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Insuficiencia Cardíaca , Hipertensión , Adulto , Aminobutiratos/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Compuestos de Bifenilo/efectos adversos , Creatinina , Combinación de Medicamentos , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Hipertensión/tratamiento farmacológico , Péptido Natriurético Encefálico/uso terapéutico , Estudios Retrospectivos , Tetrazoles/efectos adversos , Ácido Úrico , Valsartán/uso terapéuticoRESUMEN
AIMS: Our study aimed to determine the impact of genetic polymorphisms of ABCB1 and CES1 on the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We conducted a prospective study and enrolled NVAF patients treated with dabigatran. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration (PDC) and coagulation parameters including activated partial thromboplastin time (APTT) and thrombin time. Patients' demographics and clinical outcomes from scheduled follow-up visits were all recorded. Statistical analysis was performed to identify the impact of genetic polymorphisms on the PK/PD and bleeding risk of dabigatran. RESULTS: A total of 198 patients were included in analysis. For the ABCB1 polymorphisms rs4148738 and rs1045642, no significant association was found with dabigatran PK/PD. For the CES1 polymorphism rs8192935, the minor allele(C) was associated with increased trough PDCs (ANOVA: P < .001; CC vs. TT genotype, P < .001; CT vs. TT genotype, P = .014) and with APTT values at trough level (P = .015). For the CES1 polymorphism rs2244613, the minor allele(A) carriers had higher levels of trough PDC than noncarriers (ANOVA: P < .001; AA vs. CC genotype, P < .001; CA vs. CC genotype, P = .004) and increased risk for minor bleeding (P = .034; odds ratio = 2.71, 95% confidence interval 1.05-7.00). CONCLUSION: Our study indicated that the minor allele(C) on the CES1 SNP rs8192935 was associated with PDCs and APTT values at trough level. The minor allele(A) on the CES1 SNP rs2244613 was associated with increased trough PDCs and higher risk for minor bleeding in NVAF patients treated with dabigatran.
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Fibrilación Atrial , Dabigatrán , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anticoagulantes , Antitrombinas , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/genética , Hidrolasas de Éster Carboxílico/genética , Dabigatrán/efectos adversos , Hemorragia , Humanos , Polimorfismo Genético , Estudios ProspectivosRESUMEN
INTRODUCTION: Many concerns still exist regarding the safety of hydroxychloroquine (HCQ) in the treatment of Coronavirus Disease 2019 (COVID-19). OBJECTIVES: The purpose of this study was to evaluate the safety of HCQ in the treatment of COVID-19 and other diseases by performing a systematic review and meta-analysis. METHODS: Randomized controlled trials (RCTs) reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved starting from the establishment of the database till June 5, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. RESULTS: We identified 53 eligible studies involving 5496 patients. The meta-analysis indicated that the risk of adverse effects (AEs) in the HCQ group was significantly increased compared with that in the control group (RD 0.05, 95%CI, 0.02 to 0.07, P = 0.0002), and the difference was also statistically significant in the COVID-19 subgroup (RD 0.15, 95%CI, 0.07 to 0.23, P = 0.0002) as well as in the subgroup for other diseases (RD 0.03, 95%CI, 0.01 to 0.04, P = 0.003). CONCLUSIONS: HCQ is associated with a high total risk of AEs compared with the placebo or no intervention in the overall population. Given the small number of COVID-19 participants included, we should be cautious regarding the conclusion stating that HCQ is linked with an increase incidence of AEs in patients with COVID-19, which we hope to confirm in the future through well-designed and larger sample size studies.
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Tratamiento Farmacológico de COVID-19 , Hidroxicloroquina/efectos adversos , SARS-CoV-2 , Cardiotoxicidad/etiología , Tracto Gastrointestinal/efectos de los fármacos , Humanos , Evaluación de Resultado en la Atención de Salud , Sesgo de Publicación , Piel/efectos de los fármacosRESUMEN
PURPOSE: This study aimed to examine sleep quality and risk factors associated with sleep disturbance in patients undergoing total joint arthroplasty (TJA) managed with an enhanced recovery protocol from preoperatively until 12 weeks postoperatively in order to provide suggestions for improving the prevention and treatment of sleep disturbance in these patients. METHODS: The Chinese versions of the Pittsburgh Sleep Quality Index (CPSQI) and Epworth Sleepiness Scale (CESS) were used to evaluate sleep quality. Pain was measured by a visual analog scale (VAS). Neuropsychological status was also assessed, using the Center for Epidemiological Studies Depression Scale (CESD) and Zung Self-Rating Anxiety Scale (ZSAS). RESULTS: Of 107 patients (66% women), the prevalence of sleep disturbance was as high as 60% preoperatively. CPSQI score significantly increased postoperatively from baseline to 2 weeks before decreasing rapidly to a lower level than preoperative baseline. CESS scores of postoperative weeks 1 and 2 increased significantly compared with baseline and decreased significantly after 4 weeks, and a positive correlation was found between CESS and CPSQI score. VAS score significantly decreased from baseline over all time points in the postoperative period. A good sleeper group was more likely to suffer from severe sleep disturbance after surgery than a poor sleeper group with a bigger increase of CPSQI score. Multivariate logistic regression analysis indicated that pain and anxiety were risk factors associated with postoperative sleep disturbance. CONCLUSIONS: Sleep disturbance is highly prevalent among patients undergoing TJA. More attention and multimodal approaches with well-controlled pain, mental counseling, and possibly preemptive use of sleep medication may improve sleep quality in TJA patients to promote recovery.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Trastornos del Sueño-Vigilia/epidemiología , Anciano , China/epidemiología , Recuperación Mejorada Después de la Cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Factores de Riesgo , Calidad del SueñoRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Cilostazol is a specific and strong inhibitor of phosphodiesterase (PDE) type III which can suppress the platelet aggregation by increasing cyclic adenosine monophosphate (cAMP) levels. The clinical benefit of cilostazol in ACS patients suggested that the drug may have non-platelet-directed properties. Some in vitro and animal studies also indicated that the 'pleiotropic' properties of cilostazol might be related to the interaction with adenosine metabolism. Adenosine is an important regulatory metabolite and an inhibitor of platelet activation. However, no human study has been conducted to determine whether cilostazol could increase the adenosine plasma concentration in vivo. As a result, this study aimed to investigate the impact of cilostazol on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients. METHODS: We prospectively analysed 149 ACS patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents. The included patients were divided into two groups according to the presence (cilostazol group, n = 64) or absence (aspirin group, n = 85) of aspirin intolerance. The inhibition of platelet aggregation (IPA), APC and cAMP concentration was measured. Patient characteristics, medications and 30-day clinical outcomes were examined. RESULTS: Patients receiving cilostazol had a significantly higher adenosine and cAMP plasma concentration than patients receiving aspirin (3.00 ± 0.67 vs 2.56 ± 0.74 mol/L, P < .001; 28.10 ± 14.74 vs 20.48 ± 11.35 pmol/mL, P = .0014). Cilostazol was associated with a higher inhibition rate of ADP induced platelet aggregation than aspirin (63.35 ± 26.71 vs 52.2 ± 28.35, P = .036). The plasma levels of adenosine and cAMP showed a positive correlation with ADP induced platelet aggregation. WHAT IS NEW AND CONCLUSION: Cilostazol increases adenosine concentration compared with aspirin. Its potent antiplatelet effect in ACS patients may be partly mediated by adenosine.
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Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina Difosfato/sangre , Adenosina/sangre , Aspirina/uso terapéutico , Cilostazol/farmacología , Cilostazol/uso terapéutico , Anciano , Aspirina/administración & dosificación , China , Cilostazol/administración & dosificación , Clopidogrel/administración & dosificación , AMP Cíclico/sangre , Quimioterapia Combinada , Stents Liberadores de Fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función PlaquetariaRESUMEN
OBJECTIVES: Endothelial dysfunction is involved in various aspects of vascular biology and different stages of cardiovascular diseases (CVDs). Nucleotide-binding oligomerization domain-containing protein (NOD) 2, a pivotal innate immune receptor for muramyl dipeptide (MDP), has been reported to be a central regulator in CVDs. Previously, we reported that NOD2 played a leading role in MDP-triggered oxidative stress in endothelial cells (ECs). However, whether NOD2 participates in the regulatory mechanism of vascular cell adhesion molecule1 (VCAM-1) and endothelin1 (ET-1) expression was not elucidated. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with MDP for 12â¯h. mRNA expression of VCAM1 and ET1 was detected using real time polymerase chain reaction (PCR). Scrambled control small interfering RNA (siRNA) and NOD2 siRNA were transfected into HUVECs using Lipofectamine 2000 reagent (Invitrogen, Waltham, MA, USA). Furthermore, pyrrolidine dithiocarbamate was adopted to investigate the effect of nuclear factor κB (NF-κB) on NOD2-mediated VCAM1 and ET1 gene expression in MDP-treated HUVECs. RESULTS: Data showed that MDP significantly increased VCAM1 and ET1 mRNA expression, which was dependent on NOD2. In addition, NF-κB inhibition suppressed NOD2-mediated gene expression of VCAM1 and ET1. CONCLUSION: Collectively, we confirmed NOD2 aggravated VCAM1 and ET1 gene expression through NF-κB in HUVECs treated with MDP.
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FN-kappa B , Molécula 1 de Adhesión Celular Vascular , Acetilmuramil-Alanil-Isoglutamina/farmacología , Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , FN-kappa B/genética , Proteína Adaptadora de Señalización NOD2/genética , Proteína Adaptadora de Señalización NOD2/metabolismo , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is the sixth most common malignancy with limited treatment options. Hinokiflavone (HF), a natural biflavonoid, has shown to inhibit the proliferation of melanoma, whereas its antitumour effect against HCC and the underlying mechanisms remain elusive. Here, we aimed at evaluating its antitumour effect against HCC in both in vitro and in vivo. Cell counting kit 8, colony formation assay, PI/RNase staining and Western blotting revealed that HF inhibited the proliferation of HCC cells via G0/G1 cell cycle arrest with p21/p53 up-regulation. DAPI staining, Annexin V-FITC/PI staining and Western blotting confirmed that HF triggered caspase-dependent apoptosis. Moreover, HF increased the levels of mitochondrial reactive oxygen species (mtROS) and activated c-Jun N-terminal kinase (JNK) pathway, as measured by MitoSOX Red staining and Western blotting. After respectively inhibiting mtROS (Mito-TEMPO) and JNK (SP600125), HF-induced apoptosis was reversed. Additionally, Western blotting documented that HF suppressed nuclear factor kappa B (NF-κB) activity and the anti-apoptotic genes downstream, contributing to cell apoptosis. Finally, in vivo studies demonstrated that HF significantly impaired tumour growth in HCC xenograft. Collectively, these findings suggested that HF induced apoptosis through activating mtROS/JNK/caspase pathway and inhibiting NF-κB signalling, which may represent a novel therapeutic agent for treating HCC.
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Apoptosis/efectos de los fármacos , Biflavonoides/farmacología , Caspasas/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Biflavonoides/química , Carcinoma Hepatocelular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas , Ratones , FN-kappa B/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective: The main objective of the present study is to evaluate the psychometric properties of the Chinese version of Beliefs about Medicines Questionnaire-specific among asthma patients; and to assess the association between patients' belief and adherence to inhaled corticosteroid therapy. Methods: A cross-sectional survey was carried out in the asthma clinic of Zhongshan Hospital, to Fudan University (Shanghai, China) between April 2016 and March 2018. The Beliefs about Medicines Questionnaire-specific was translated into Chinese according to international guidelines. Internal consistency, test-retest reliability, and confirmatory factor analysis were calculated to validate the Beliefs about Medicines Questionnaire-specific. The relationship between the adherence and the belief subscale were assessed using Kruskal-Wallis test. Results: Two hundred and seventeen patients were recruited in this study. The Beliefs about Medicines Questionnaire-specific was deemed reliable based on the results of Cronbach's alpha coefficient and test-retest intraclass correlation coefficient (ICC, ICC= 0.759). Confirmatory factor analysis showed acceptable model fit for the two-factor model. Patients' compliance was closely related to their belief about inhaled corticosteroid. The adherence rates were highest for the accepting groups, and lowest for the skeptical groups. Higher adherence was significantly associated with higher necessity-concerns differential (p = .001) and lower concern (p = .004). Conclusions: The Chinese version of the Beliefs about Medicines Questionnaire-specific can be used as a reliable tool by the clinicians to identify beliefs and behaviors of individual to improve adherence in Chinese patients.
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Asma/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Cumplimiento de la Medicación/psicología , Psicometría/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Femenino , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Psicometría/estadística & datos numéricos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios/estadística & datos numéricos , Adulto JovenRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Although ticagrelor has been well-known to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), and its effectiveness and safety have not been well evaluated in Chinese patients. This study aimed to evaluate the effectiveness and safety of ticagrelor in Chinese patients. In order to find potential effect modifiers on the drug effects, a decision tree method was performed to detect interactions between treatment and patient characteristics in an automatic and systematic manner. METHODS: This retrospective study included acute coronary syndrome (ACS) patients who underwent PCI and received either ticagrelor (N = 250) or clopidogrel (N = 291) while hospitalized between August 2014 and August 2015. After propensity score matching, Kaplan-Meier analysis was used to study the event-free survival against major adverse cardiovascular events (MACE, primary efficacy outcome, defined as the composite of cardiac death, non-fatal myocardial infarction [MI], stroke, restenosis and target vessel revascularization [TVR]), re-hospitalization, the need for urgent re-PCI (secondary efficacy outcome) and bleeding events (safety outcome) within 12 months of the PCI date. To search for effect modifiers of the two antiplatelet therapies, a machine-learning decision tree algorithm was conducted to predict re-hospitalization status. RESULTS: After propensity score matching (N = 442), ticagrelor and clopidogrel had no significant difference in MACE, re-hospitalization and bleeding. The decision tree analysis showed that the number of diseased vessels modulated the effect of ticagrelor and clopidogrel on re-hospitalization rates. In single-vessel disease (SVD) patients, ticagrelor was associated with lower hazards than clopidogrel for all efficacy outcomes: MACE (HR = 0.190, 95% CI: 0.042-0.866), re-hospitalization (HR = 0.296, 95% CI: 0.108-0.808), urgent re-PCI (HR = 0.249, 95% CI: 0.069-0.895), bleeding (HR = 1.006, 95% CI: 0.063-16.129). However, in multi-vessel disease (MVD) patients, the two treatments did not show significant difference. WHAT IS NEW AND CONCLUSION: In the general patient population, there was no significant difference between ticagrelor and clopidogrel on the hazard of MACE. However, ticagrelor achieved a better effectiveness than clopidogrel in patients with SVD. This pilot study provides scientific basis to call for a large-scale prospective study in this population.
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Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/administración & dosificación , Intervención Coronaria Percutánea/métodos , Ticagrelor/administración & dosificación , Anciano , Algoritmos , Pueblo Asiatico , Clopidogrel/efectos adversos , Minería de Datos , Árboles de Decisión , Femenino , Hemorragia/inducido químicamente , Hospitalización , Humanos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Proyectos Piloto , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Retrospectivos , Ticagrelor/efectos adversosRESUMEN
Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.
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Proteínas de Unión al ADN/antagonistas & inhibidores , Células Endoteliales/patología , MicroARNs/farmacología , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Antioxidantes/farmacología , Dioxigenasas/antagonistas & inhibidores , Células Endoteliales de la Vena Umbilical Humana , Humanos , MicroARNs/genética , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , TransfecciónRESUMEN
Giant coronary artery aneurysm (CAA) is a rare disorder, defined as coronary artery dilatation, in which the diameter of the coronary artery exceeds more than 1.5 times of its normal size. The most common cause of CAA is coronary atherosclerosis for adults and Kawasaki disease (KD) for children and adolescents (especially for the giant CAA that occurred in adolescence). CAA complications include thrombus, acute myocardial infarction (AMI), vasospasm, rupture, ischemia, heart failure, and arrhythmia. So, antithrombotic therapy is crucial for patients with giant CAA.Although giant CAA has been reported in some cases before, few of these cases described antithrombotic therapy particularly, let alone informed direct oral anticoagulant (DOAC) use in these patients. Here, we report a case of a young patient with acute coronary artery disease caused by huge CAA. Rivaroxaban combined with clopidogrel was used for his antithrombotic therapy. Moreover, we reviewed the existing reports to provide an overview of antithrombotic treatment in patients with giant CAA.
Asunto(s)
Clopidogrel/uso terapéutico , Aneurisma Coronario/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/uso terapéutico , Humanos , Masculino , Adulto JovenRESUMEN
PURPOSE: The purpose of this study was to analyze the association between bleeding events and coagulation assays including activated partial thromboplastin time (APTT) and prothrombin time (PT), and to determine the risk factors for bleeding in Chinese patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran. METHODS: We conducted a retrospective cohort study including NVAF patients receiving dabigatran 110 mg twice daily between March 2016 and November 2017. We obtained the clinical features and demographic data from the medical records and compared the baseline characteristics of the bleeding group and the no bleeding group. Receiver operating characteristic(ROC) curves and a logistic regression model were used to determine the relation between APTT and bleeding events and the predictors of bleeding. Model performance was evaluated using the derivation cohort and an independent validation cohort by area under the ROC curve (AUC). RESULTS: A total of 346 patients were included and bleeding events occurred in 39 (11.2%) patients. Patients with age over 65 years (OR = 2.56 [95% CI 1.20-5.43]), hypertension (OR = 2.42 [95% CI 1.11-5.26]), decreased renal function (OR = 4.27 [95% CI 1.22-14.91]) and with concomitant use of an antiplatelet drug (OR = 3.53 [95% CI 1.28-9.74]) showed higher risk for bleeding, and APTT value of the bleeding group was higher than the no bleeding group (P = 0.014). By ROC analysis we found that the appropriate overall cut-off value the of APTT ratio was 1.30, with a sensitivity of 72% and specificity of 58%. Multivariate logistic regression showed that higher age (P = 0.003; OR = 1.05 [95% CI 1.02-1.09]) and APTT ratio > 1.30 (P = 0.002; OR = 3.20 [95% CI 1.23-6.73]) were independent risk factors for bleeding in patients with dabigatran therapy. The logistic regression model exhibited moderate discrimination ability, with an AUC of 0.73 [95% CI 0.65-0.81] and 0.77 [95% CI 0.59-0.96] in the derivation cohort (n = 346) and the validation cohort (n = 71) respectively. CONCLUSIONS: Our study demonstrated that APTT ratio > 1.30 (at trough level) and higher age were independent risk factors for bleeding, and the logistic regression model based on these two predictors showed moderate performance, which may be useful for assessment of bleeding risk in NVAF patients with dabigatran therapy.
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Antitrombinas/efectos adversos , Fibrilación Atrial/sangre , Coagulación Sanguínea/efectos de los fármacos , Dabigatrán/efectos adversos , Hemorragia/inducido químicamente , Factores de Edad , Anciano , Antitrombinas/administración & dosificación , Antitrombinas/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Estudios de Cohortes , Dabigatrán/administración & dosificación , Dabigatrán/uso terapéutico , Femenino , Hemorragia/sangre , Hemorragia/epidemiología , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Tiempo de Tromboplastina Parcial , Valor Predictivo de las Pruebas , Curva ROC , Estudios RetrospectivosRESUMEN
The type-I insulin-like growth factor receptor (IGF-IR) is overexpressed in endometrial cancer. High IGF-IR expression was considered as an important prognostic factor for tumor progression. The purpose of this study was to investigate the role and molecular mechanism of IGF-IR inhibitor picropodophyllin (PPP) in the growth and development of endometrial cancer. High expression of IGF-IR was observed in endometrial cancer tissues, as well as in ECC-1 and KLE cell lines. PPP suppressed the number of clones of ECC-1 and KLE cell lines; however, it had no significant effect on HEC-1-A cell line, which expressed lower IGF-IR than ECC-1 and KLE cell lines. Furthermore, PPP reduced cell proliferation capacity, inhibited the IGF-IR mRNA expression, and suppressed protein phosphorylation of IGF-IR and Akt in the three cell lines. In addition, PPP inhibited the protein expression of survivin in KLE cell line after 1 h of exposure, though this effect did not last for prolonged time. In conclusion, IGF-IR was mostly overexpressed in type I endometrial cancer. High IGF-IR expression was an important prognostic factor of tumor progression. PPP mediated the down-regulation of IGF-IR phosphorylation and inhibited cell proliferation via the PI3K/Akt signal pathway. PPP may have the potential to become a clinical treatment target in endometrial carcinoma.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Neoplasias Endometriales/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Podofilotoxina/análogos & derivados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Fosforilación/efectos de los fármacos , Podofilotoxina/farmacología , Pronóstico , Receptor IGF Tipo 1/antagonistas & inhibidores , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Survivin/genética , Survivin/metabolismoRESUMEN
AIMS: The objective of the present study was to investigate the current situation concerning, and risk factors for, vancomycin (VAN)-induced acute kidney injury (VI-AKI) in elderly Chinese patients, to assess outcomes and risk factors in patients who have developed VI-AKI, in order to provide suggestions for improving the prevention and treatment of this condition in these patients. METHOD: We retrospectively identified elderly older inpatients who had received four or more doses of VAN treatment. We compared patients with VI-AKI with those who received VAN treatment and had not developed AKI (NO-AKI). We defined VI-AKI as developing AKI during VAN therapy or within 3 days after withdrawal of VAN. RESULTS: A total of 647 out of 862 elderly inpatients were included in the study. Among those excluded, in 89.3% of cases (192/215) this was because of lack of data on serum creatinine (SCr). Among included patients, 32.5% (210/647) of patients received therapeutic drug monitoring (TDM) during VAN therapy. In 66.9% of cases (424/634), there was insufficient TDM, and in 3.9% (25/634) this was appropriate. A total of 102 patients had confirmed VI-AKI, with an incidence of 15.8% (102/647). Multiple logistic regression analysis revealed that hyperuricaemia [odds ratio (OR) = 3.045; P = 0.000)], mechanical ventilation (OR = 1.906; P = 0.022) and concomitant vasopressor therapy (OR = 1.919; P = 0.027) were independent risk factors for VI-AKI; higher serum albumin (OR = 0.885; P = 0.000) was determined to be an independent protective factor for VI-AKI. CONCLUSIONS: For the elderly Chinese patients treated with VAN, there was insufficient monitoring of SCr, too little use of VAN TDM, and lower rate of patients whose VAN though serum concentrations were not obtained at the correct time. We recommend that hospital managers increase investment in clinical pharmacists, to strengthen professional management. Patients with concomitant hyperuricaemia and on mechanical ventilation and vasopressor therapy should be paid more attention, and a higher serum albumin was determined to be an independent protective factor for VI-AKI.
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Lesión Renal Aguda/epidemiología , Antibacterianos/efectos adversos , Monitoreo de Drogas/estadística & datos numéricos , Hiperuricemia/epidemiología , Vancomicina/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Factores de Edad , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Riñón/efectos de los fármacos , Riñón/fisiopatología , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Persona de Mediana Edad , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Vasoconstrictores/administración & dosificaciónRESUMEN
BACKGROUND: Circulating microRNAs (miRs) may act as diagnostic and prognostic biomarkers for cardiovascular events in coronary artery bypass graft (CABG) surgery patients. This study measured changes in cardiac- and muscle-related miRs and cardiac and inflammatory biomarkers in acute coronary syndrome patients undergoing CABG surgery as well as investigated the correlations between these indicators. METHODS: Creatine kinase-MB (CK-MB), brain natriuretic peptide (BNP), cardiac troponin T (cTnT), interleukin-6 (IL-6), IL-8, IL-10, high-sensitivity C-reactive protein, and tumor necrosis factor-α were measured, and real-time quantitative polymerase chain reaction was performed to determine the plasma levels of miR-1, miR-133a, miR-208a, and miR-499 before and after surgery in 27 acute coronary syndrome patients. Left ventricular ejection fraction was also analyzed in a 3-month follow-up. RESULTS: miR-1, miR-133a, and miR-208a increased significantly (P = 0.0011; P = 0.0057; P = 0.0197, respectively) and the CK-MB, cTnT, BNP, and IL-6 levels were augmented after surgery. miR-133a, miR-208a, and miR-499 positively correlated with cTnT (r = 0.302, P = 0.027; r = 0.326, P = 0.016; r = 0.298, P = 0.029, respectively), but only miR-208a significantly correlated with CK-MB (r = 0.278, P = 0.041). miR-133a and miR-208a were significantly related to IL-6 (r = 0.287, P = 0.036; r = 0.292, P = 0.032, respectively). However, there were no significant associations between miRs and BNP or 3-month left ventricular ejection fraction. CONCLUSIONS: CABG surgery-induced myocardial reperfusion damage and subsequent inflammation were related to changes in miR-1, miR-133a, and miR-208a. Notably, miR-208a was the only indicator associated with CK-MB, cTnT, and IL-6, which may reflect heart injury and inflammation in these patients.