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1.
Front Neurol ; 13: 916966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071896

RESUMO

Background: Stroke is the second leading cause of death worldwide, causing a considerable disease burden. Ischemic stroke is more frequent, but haemorrhagic stroke is responsible for more deaths. The clinical management and treatment are different, and it is advantageous to classify their risk as early as possible for disease prevention. Furthermore, retinal characteristics have been associated with stroke and can be used for stroke risk estimation. This study investigated machine learning approaches to retinal images for risk estimation and classification of ischemic and haemorrhagic stroke. Study design: A case-control study was conducted in the Shenzhen Traditional Chinese Medicine Hospital. According to the computerized tomography scan (CT) or magnetic resonance imaging (MRI) results, stroke patients were classified as either ischemic or hemorrhage stroke. In addition, a control group was formed using non-stroke patients from the hospital and healthy individuals from the community. Baseline demographic and medical information was collected from participants' hospital medical records. Retinal images of both eyes of each participant were taken within 2 weeks of admission. Classification models using a machine-learning approach were developed. A 10-fold cross-validation method was used to validate the results. Results: 711 patients were included, with 145 ischemic stroke patients, 86 haemorrhagic stroke patients, and 480 controls. Based on 10-fold cross-validation, the ischemic stroke risk estimation has a sensitivity and a specificity of 91.0% and 94.8%, respectively. The area under the ROC curve for ischemic stroke is 0.929 (95% CI 0.900 to 0.958). The haemorrhagic stroke risk estimation has a sensitivity and a specificity of 93.0% and 97.1%, respectively. The area under the ROC curve is 0.951 (95% CI 0.918 to 0.983). Conclusion: A fast and fully automatic method can be used for stroke subtype risk assessment and classification based on fundus photographs alone.

2.
J Clin Med ; 11(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35628812

RESUMO

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death worldwide, constituting a growing health and social burden. People with cardiometabolic disorders are more likely to develop CHD. Retinal image analysis is a novel and noninvasive method to assess microvascular function. We aim to investigate whether retinal images can be used for CHD risk estimation for people with cardiometabolic disorders. METHODS: We have conducted a case-control study at Shenzhen Traditional Chinese Medicine Hospital, where 188 CHD patients and 128 controls with cardiometabolic disorders were recruited. Retinal images were captured within two weeks of admission. The retinal characteristics were estimated by the automatic retinal imaging analysis (ARIA) algorithm. Risk estimation models were established for CHD patients using machine learning approaches. We divided CHD patients into a diabetes group and a non-diabetes group for sensitivity analysis. A ten-fold cross-validation method was used to validate the results. RESULTS: The sensitivity and specificity were 81.3% and 88.3%, respectively, with an accuracy of 85.4% for CHD risk estimation. The risk estimation model for CHD with diabetes performed better than the model for CHD without diabetes. CONCLUSIONS: The ARIA algorithm can be used as a risk assessment tool for CHD for people with cardiometabolic disorders.

3.
Science ; 374(6575): 1586-1593, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34726479

RESUMO

The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.


Assuntos
Tratamento Farmacológico da COVID-19 , Lactamas/farmacologia , Lactamas/uso terapêutico , Leucina/farmacologia , Leucina/uso terapêutico , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Prolina/farmacologia , Prolina/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Inibidores de Protease Viral/farmacologia , Inibidores de Protease Viral/uso terapêutico , Administração Oral , Animais , COVID-19/virologia , Ensaios Clínicos Fase I como Assunto , Coronavirus/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Lactamas/administração & dosagem , Lactamas/farmacocinética , Leucina/administração & dosagem , Leucina/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Nitrilas/administração & dosagem , Nitrilas/farmacocinética , Prolina/administração & dosagem , Prolina/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , SARS-CoV-2/fisiologia , Inibidores de Protease Viral/administração & dosagem , Inibidores de Protease Viral/farmacocinética , Replicação Viral/efeitos dos fármacos
4.
Medicine (Baltimore) ; 100(31): e26846, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397858

RESUMO

ABSTRACT: To estimate National Institutes of Health Stroke Scale (NIHSS) grading of stroke patients with retinal characteristics.A cross-sectional study was conducted in Shenzhen Traditional Chinese Medicine Hospital. Baseline information and retinal photos were collected within 2 weeks of admission. An NIHSS score was measured for each patient by trained doctors. Patients were classified into 0 to 4 score group and 5 to 42 score group for analysis. Three multivariate logistic models, with traditional clinical characteristics alone, with retinal characteristics alone, and with both, were built.For clinical characteristics, hypertension duration is statistically significantly associated with higher NIHSS score (P = .014). Elevated total homocysteine levels had an OR of 0.456 (P = .029). For retinal characteristics, the fractal dimension of the arteriolar network had an OR of 0.245 (P < .001) for the left eyes, and an OR of 0.417 (P = .009) for right eyes. The bifurcation coefficient of the arteriole of the left eyes had an OR of 2.931 (95% CI 1.573-5.46, P = .001), the nipping of the right eyes had an OR of 0.092 (P = .003) showed statistical significance in the model.The area under receiver-operating characteristic curve increased from 0.673, based on the model with clinical characteristics alone, to 0.896 for the model with retinal characteristics alone and increased to 0.931 for the model with both clinical and retinal characteristics combined.Retinal characteristics provided more information than clinical characteristics in estimating NIHSS grading and can provide us with an objective method for stroke severity estimation.


Assuntos
Hipertensão , Vasos Retinianos/diagnóstico por imagem , Prevenção Secundária/métodos , Índice de Gravidade de Doença , Acidente Vascular Cerebral , China/epidemiologia , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Recidiva , Projetos de Pesquisa , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
5.
Medicine (Baltimore) ; 99(26): e20830, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590771

RESUMO

To identify the clinical risk factors and investigate the efficacy of a classification model based on the identified factors for predicting 2-year recurrence after ischemic stroke.From June 2017 to January 2019, 358 patients with first-ever ischemic stroke were enrolled and followed up in Shenzhen Traditional Chinese Medicine Hospital. Demographic and clinical characteristics were recorded by trained medical staff. The outcome was defined as recurrence within 2 years. A multivariate logistic regression model with risk factors and their interaction effects was established and evaluated.The mean (standard deviation) age of the participants was 61.6 (12.1) years, and 101 (28.2%) of the 358 patients were female. The common comorbidities included hypertension (286 patients, 79.9%), diabetes (148 patients, 41.3%), and hyperlipidemia (149 patients, 41.6%). The 2-year recurrence rate was 30.7%. Of the 23 potential risk factors, 10 were significantly different between recurrent and non-recurrent subjects in the univariate analysis. A multivariate logistic regression model was developed based on 10 risk factors. The significant variables include diabetes mellitus, smoking status, peripheral artery disease, hypercoagulable state, depression, 24 h minimum systolic blood pressure, 24 h maximum diastolic blood pressure, age, family history of stroke, NIHSS score status. The area under the receiver operating characteristic curve (ROC) was 0.78 (95% confidence interval: 0.726-0.829) with a sensitivity of 0.61 and a specificity of 0.81, indicating a potential predictive ability.Ten risk factors were identified, and an effective classification model was built. This may aid clinicians in identifying high-risk patients who would benefit most from intensive follow-up and aggressive risk factor reduction.The clinical trial registration number: ChiCTR1800019647.


Assuntos
Isquemia Encefálica/classificação , Recidiva , Acidente Vascular Cerebral/classificação , Idoso , Isquemia Encefálica/epidemiologia , Distribuição de Qui-Quadrado , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
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