RESUMO
OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling â¼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving â¼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (â¼ 1,500 IPE: â¼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.
Assuntos
Aterosclerose/complicações , COVID-19/complicações , Doenças Cardiovasculares/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Doenças Cardiovasculares/complicações , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/complicações , Infecções Respiratórias/virologiaRESUMO
Understanding of the renin-angiotensin system (RAS) has changed remarkably over the past decade. Renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II), and Ang II receptors are the main components of the RAS. Recent studies identified the ACE2/Ang 1-7/Mas receptor axis, which counter-regulates the classical RAS. Many studies have examined the effects of the RAS on the progression of cardiovascular disease and chronic kidney disease (CKD). In addition, many studies have documented increased levels of ACE in hemodialysis (HD) patients, raising concerns about the negative effects of RAS activation on the progression of renal disease. Elevated ACE increases the level of Ang II, leading to vasoconstriction and cell proliferation. Ang II stimulation of the sympathetic system leads to renal and cardiovascular complications that are secondary to uncontrolled hypertension. This review provides an overview of the RAS, evaluates new research on the role of ACE2 in dialysis, and reviews the evidence for potentially better treatments for patients undergoing HD. Further understanding of the role of ACE and ACE2 in HD patients may aid the development of targeted therapies that slow the progression of CKD and cardiovascular disease.
Assuntos
Falência Renal Crônica/metabolismo , Diálise Renal , Sistema Renina-Angiotensina , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2 , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Peptidil Dipeptidase A/metabolismoRESUMO
The aim of this study was to determine specific pattern of port site microbial colonisation, sensitivity and resistance to different antibiotics of bacteria isolated from port site infection (PSI) in low risk patients after elective laparoscopic cholecystectomy in surgical wards at tertiary care hospital of Kashmir. This is a prospective study. The study included 675 consecutive patients of postoperative PSI after elective laparoscopic cholecystectomy for symptomatic cholelithiasis over a period of 12 months. Culture swabs were taken from port sites with signs of PSI and transported to the microbiology laboratory. The positive swab cultures were subjected to antibiotic susceptibility test. The data obtained was analysed by using appropriate statistical analytical tests. The incidence of PSI after elective laparoscopic cholecystectomy is 6·7%. The commonest organism responsible for PSI is pseudomonas, 19 (42·2%) cases. Most of the strains of organisms isolated were resistant to commonly used antibiotics in the hospital,pseudomonas was found 100% resistant to the combination of ampicillin + sulbactum and ceftriaxone and it was sensitive to imipenem, amikacin and vancomycin in 89·47,57 and 52·63% of cases respectively. Our study will be helpful in choosing effective empirical prophylactic antibiotic therapy in cases of elective laparoscopic cholecystectomy and will have a great impact on morbidity and mortality in them because of PSI.
Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Colelitíase/cirurgia , Farmacorresistência Bacteriana , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/microbiologia , Antibioticoprofilaxia , Procedimentos Cirúrgicos Eletivos , Humanos , Incidência , Índia/epidemiologia , Staphylococcus aureus Resistente à Meticilina , Estudos Prospectivos , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/prevenção & controle , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
Robotics and artificial intelligence have played a significant role in developing assistive technologies for people with motor disabilities. Brain-Computer Interface (BCI) is a communication system that allows humans to communicate with their environment by detecting and quantifying control signals produced from different modalities and translating them into voluntary commands for actuating an external device. For that purpose, classification the brain signals with a very high accuracy and minimization of the errors is of profound importance to the researchers. So in this study, a novel framework has been proposed to classify the binary-class electroencephalogram (EEG) data. The proposed framework is tested on BCI Competition IV dataset 1 and BCI Competition III dataset 4a. Artifact removal from EEG data is done through preprocessing, followed by feature extraction for recognizing discriminative information in the recorded brain signals. Signal preprocessing involves the application of independent component analysis (ICA) on raw EEG data, accompanied by the employment of common spatial pattern (CSP) and log-variance for extracting useful features. Six different classification algorithms, namely support vector machine, linear discriminant analysis, k-nearest neighbor, naïve Bayes, decision trees, and logistic regression, have been compared to classify the EEG data accurately. The proposed framework achieved the best classification accuracies with logistic regression classifier for both datasets. Average classification accuracy of 90.42% has been attained on BCI Competition IV dataset 1 for seven different subjects, while for BCI Competition III dataset 4a, an average accuracy of 95.42% has been attained on five subjects. This indicates that the model can be used in real time BCI systems and provide extra-ordinary results for 2-class Motor Imagery (MI) signals classification applications and with some modifications this framework can also be made compatible for multi-class classification in the future.
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Algoritmos , Inteligência Artificial , Humanos , Teorema de Bayes , Modelos Logísticos , EletroencefalografiaRESUMO
Stock market forecasting is one of the most challenging problems in today's financial markets. According to the efficient market hypothesis, it is almost impossible to predict the stock market with 100% accuracy. However, Machine Learning (ML) methods can improve stock market predictions to some extent. In this paper, a novel strategy is proposed to improve the prediction efficiency of ML models for financial markets. Nine ML models are used to predict the direction of the stock market. First, these models are trained and validated using the traditional methodology on a historic data captured over a 1-day time frame. Then, the models are trained using the proposed methodology. Following the traditional methodology, Logistic Regression achieved the highest accuracy of 85.51% followed by XG Boost and Random Forest. With the proposed strategy, the Random Forest model achieved the highest accuracy of 91.27% followed by XG Boost, ADA Boost and ANN. In the later part of the paper, it is shown that only classification report is not sufficient to validate the performance of ML model for stock market prediction. A simulation model of the financial market is used in order to evaluate the risk, maximum draw down and returns associate with each ML model. The overall results demonstrated that the proposed strategy not only improves the stock market returns but also reduces the risks associated with each ML model.
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Investimentos em Saúde , Aprendizado de Máquina , Humanos , Simulação por Computador , Algoritmo Florestas Aleatórias , PesquisadoresRESUMO
BACKGROUND: The impact of the novel coronavirus disease 2019 (COVID-19) pandemic on diet and nutrition among older adults with chronic medical conditions have not been well-described. METHODS: We conducted a survey addressing (1) food access, (2) diet quality and composition, (3) nutritional understanding, and (4) attitudes towards research among adults with heart failure (HF) within an integrated health system. Adults (≥18 years) with diagnosed HF and at least one prior hospitalization for HF within the last 12 months were approached to complete the survey electronically or by mail. Outcomes included all-cause and HF-specific hospitalizations and all-cause death was ascertained via the electronic health record. RESULTS: Among 1212 survey respondents (32.5% of eligible patients) between May 18, 2020 and September 30, 2020, mean ± SD age was 77.9 ± 11.4 years, 50.1% were women, and median (25th-75th) left ventricular ejection fraction was 55% (40%-60%). Overall, 15.1% of respondents were food insecure, and only 65% of participants answered correctly more than half of the items assessing nutritional knowledge. Although most respondents were willing to participate in future research, that number largely declined for studies requiring blood draws (32.2%), study medication (14.4%), and/or behavior change (27.1%). Food security, diet quality, and nutritional knowledge were not independently associated with outcomes at 90 or 180 days. CONCLUSION: In a cohort of older adults with HF and multiple comorbidities, a significant proportion reported issues with food access, diet quality, and nutritional knowledge during the COVID-19 pandemic. Future research should evaluate interventions targeting these domains in at-risk individuals.
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COVID-19 , Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Atitude , Dieta , Feminino , Segurança Alimentar , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Valor Nutritivo , Pandemias , SARS-CoV-2 , Volume Sistólico , Função Ventricular EsquerdaRESUMO
OBJECTIVES: The aim of this study was to determine the prognostic utility of baseline functional status and its impact on the outcomes of transcatheter mitral valve repair (TMVr) in patients with heart failure (HF) with secondary mitral regurgitation (SMR). BACKGROUND: The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial demonstrated that TMVr with the MitraClip in patients with HF with moderate to severe or severe SMR improved health-related quality of life. The clinical utility of a baseline assessment of functional status for evaluating prognosis and identifying candidates likely to derive a robust benefit from TMVr has not been previously studied in patients with HF with SMR. METHODS: The COAPT study was a multicenter, randomized, controlled, parallel-group, open-label trial of TMVr with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with HF, left ventricular ejection fraction 20% to 50%, and moderate to severe or severe SMR. Baseline functional status was assessed by 6-min walk distance (6MWD). RESULTS: Patients with 6MWD less than the median (240 m) were older, were more likely to be female, and had more comorbidities. After multivariate modeling, age (p = 0.005), baseline hemoglobin (p = 0.007), and New York Heart Association functional class III/IV symptoms (p < 0.0001) were independent clinical predictors of 6MWD. Patients with 6MWD <240 m versus ≥240 m had a higher unadjusted and adjusted rate of the 2-year composite of all-cause death or HF hospitalization (64.4% vs. 48.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.19 to 1.98; p = 0.001). However, there was no interaction between baseline 6MWD and the relative effectiveness of TMVr plus GDMT versus GDMT alone with respect to the composite endpoint (p = 0.633). CONCLUSIONS: Baseline assessment of functional capacity by 6MWD was a powerful discriminator of prognosis in patients with HF with SMR. TMVr with the MitraClip provided substantial improvements in clinical outcomes for this population irrespective of baseline functional capacity.
Assuntos
Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Feminino , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Qualidade de Vida , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
BACKGROUND: Infectious diseases are more frequent in diabetic patients, leading to increased morbidity and mortality. Endotoxemia affects glucose metabolism and lipolytic capacity. The aims of the present study were to determine whether endotoxemia exacerbates metabolic features (adipose inflammation, adipogenesis, and insulin resistance [IR]) in an animal model of diabetes (i.e. db/db mice) after acute infection and the effects of pioglitazone. METHODS: Female db/db mice treated with pioglitazone (3 and 30 mg/kg, p.o.) for 14 days were challenged with lipopolysaccharide (LPS; 200 µg/kg), followed by an oral glucose tolerance test (OGTT). Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression of genes in white adipose tissue (WAT) involved in: (i) adipogenesis (lipoprotein lipase [Lpl], fatty acid binding protein-4 [Ap2] and adiponectin [Adipoq]); (ii) insulin signaling (peroxisome proliferator-activated receptor gamma [Pparg], suppressor of cytokine signaling 3 [Socs3], solute carrier family 2 [facilitated glucose transporter], member 4 [Slc2a4]); and (iii) inflammation (tumor necrosis factor [Tnf], interleukin-6 [Il6], monocyte chemoattractant protein-1 [Ccl2], cyclo-oxygenase-2 [prostaglandin-endoperoxide synthase 2; Ptgs2]). RESULTS: Experimental endotoxemia downregulated mRNA expression of Pparg, Slc2a4, Adipoq, Lpl, and Ap2, which coincided with upregulation of Il6, Tnf, Ccl2, Ptgs2, and Socs3 expression. Pioglitazone dose-dependently decreased Tnf, Il6, Ccl2, Ptgs2, and Socs3 expression in WAT, in association with upregulation of Lpl, Ap2, Slc2a4, and Adipoq expression, indicating improvement in endotoxin-induced IR. CONCLUSIONS: The findings suggest that LPS challenge exacerbates IR in db/db mice by altering the expression of genes in WAT involved in adipogenesis and inflammation, which is effectively controlled by pioglitazone treatment.
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Tecido Adiposo Branco/efeitos dos fármacos , Diabetes Mellitus/metabolismo , Endotoxemia/metabolismo , Obesidade/metabolismo , Tiazolidinedionas/farmacologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus/genética , Endotoxemia/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Teste de Tolerância a Glucose , Hipoglicemiantes/farmacologia , Inflamação/genética , Inflamação/metabolismo , Inflamação/prevenção & controle , Resistência à Insulina/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/genética , PioglitazonaRESUMO
Emerging evidence suggest that tumor necrosis factor (TNF)-α plays a major role in pathogenesis of auto-immune hepatitis (AIH) induced liver injury. Blockade of TNF-α synthesis or bio-activity protects against experimental AIH. TNF-α converting enzyme (TACE) is a member of the ADAM (a disintegrin and metalloproteinase) family which processes precursor TNF-α to release soluble TNF-α. We hypothesized that selective inhibition of TACE might protect AIH. To investigate this, we studied the effects of a selective TACE inhibitor DPC-333 on murine model of liver injury and fibrosis induced with concanavalin A (Con A). Pre-treatment with DPC-333 significantly suppressed plasma alanine transaminase, aspartate transaminase and cytokines such as TNF-α, interferon (IFN)-γ, interleukin (IL)-2 and IL-6 levels due to acute Con A challenge. Interestingly; DPC-333 inhibited liver poly (ADP-ribose) polymerase (PARP)-1 activity which was associated with reduced number of necrotic hepatocytes in histological examination and mortality associated with Con A. In fibrosis study, repeated Con A administration significantly up-regulated liver collagen deposition as assessed by measurement of hydroxyproline content which was further confirmed in liver histology with Masson's trichrome staining. Treatment with 30mg/kg of DPC-333 was able to suppress liver hydroxyproline and fibrous tissue proliferation which corroborated well with inhibition in expression of pro-fibrotic genes such as tissue inhibitor of metalloproteinase (TIMP)-1 and transforming growth factor (TGF)-ß1. These observations suggest that selective TACE inhibition is an effective approach for the treatment of both immune mediated hepatic inflammation and fibrosis.