The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase III trial.
Evolocumab, a fully human monoclonal ...antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials.
Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; or oral placebo and evolocumab 420 mg monthly.
A total of 614 patients were randomized and administered doses. Evolocumab treatment reduced LDL-C from baseline, on average, by 55% to 57% more than placebo and 38% to 40% more than ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment also favorably altered other lipoprotein levels. Treatment-emergent adverse events (AEs), muscle-related AEs, and laboratory abnormalities were comparable across treatment groups.
In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 MENDEL-2; NCT01763827).
Purpose
To evaluate the three-dimensional choroidal vascularity index (CVI) in the eyes with treatment-naïve acute central serous chorioretinopathy (CSC) using swept-source optical coherence ...tomography (SS OCT).
Methods
In this prospective cross-sectional study, OCT and OCT angiography covered an area of 12 × 12 mm centered on the fovea. Three-dimensional CVI was defined as the ratio of the choroidal vascular luminal volume to the total choroidal volume. The location of pigment epithelial detachment (PED) and the area with abnormal perfusion at choriocapillary layer were compared with the distribution of the three-dimensional CVI.
Results
Thirty-two eyes with treatment-naïve acute CSC, 18 fellow eyes, and 48 control eyes were enrolled. Three-dimensional CVI had good repeatability on control eyes, with a coefficient of variation of 0.166. The mean CVI in the scan area was 0.35 in the eyes with CSC, 0.34 in the fellow eyes of CSC, and 0.30 in the control eyes. The overall CVI in the control eyes was significantly lower than that in the eyes with CSC and that in fellow eyes (
P
< 0.001 and
P
= 0.006, respectively). The eyes with CSC and the fellow eyes had significantly higher CVI values at the posterior pole and the drainage routes of choroidal veins. In the eyes with CSC, PEDs and choriocapillary with abnormal perfusion colocalized with the dilated choroidal vessels, which had high three-dimensional CVI values.
Conclusion
Increased three-dimensional CVI suggested an increased vascular component in the eyes with CSC and in fellow eyes. The three-dimensional CVI is a useful imaging marker of choroidal diseases that volumetrically assesses the choroidal vasculature and might advance our understanding of CSC pathophysiology.
This paper comprehensively elaborates the differences in normal body and mind levels of high-altitude migrant college students between low-altitude and high-altitude regions, as well as the changes ...in normal body and mind levels of high-altitude migrant college students during their migration to high-altitude regions and the adaptation mechanism, so as to reveal the influence of altitude on the normal body and mind of high-altitude migrant college students and provide a comprehensive theoretical basis for the evaluation and standardization of normal body and mind levels of high-altitude migrant college students from different altitude regions. In view of the current situation of martial arts morning practice of college students and its problems, and the objective analysis of the reasons for the poor effect of martial arts morning practice, the article adopts the artificial neural network method and establishes a comprehensive evaluation model of normal body and mind of high-altitude migrant college students who perform martial arts morning practice based on the artificial neural network method, circumvents the empirical and arbitrary nature of the traditional threshold setting, takes the improvement of students' physical fitness as the guiding ideology, establishes The concept of a new model of cultivating the awareness of college students' martial arts morning practice, which includes relevant organizations and establishing a guarantee system, improving supervision, strengthening guidance, increasing the investment in hardware for students' physical exercise, and playing the role of associations. In the experimental validation, we find the data connection between each test sample and determine the threshold value of each index, and finally establish a scientific comprehensive evaluation model of normal body and mind of high-altitude migrant college students in martial arts morning practice, which makes up for the shortcomings of the original research method and evaluation model.
To explore effective factors of surgical effect for patients with cleft lip and palate, and to construct the predictive model of surgical effect, which provide reference for improving the effect of ...cleft lip and palate surgery.
This study has been ethically reviewed and approved by the Medical Ethics Committee of Guiyang Stomatological Hospital before the study began.A total of 997 cases of cleft lip and palate surgical treatment in Guiyang Stomatological Hospital from 2015 to 2020 were collected. Logistic regression analysis was used to analyze the factors influencing the surgical outcome, and a score system was established by assigning values to the influencing factors using the nomogram. Data of 110 patients were verified, and decision curve analysis was used to evaluate the predicted results.
Logistic regression analysis showed that the number of surgeries, surgical methods, breast milk, prenatal examination, nutrition during pregnancy and labor intensity during pregnancy were independent risk factors for poor surgical results (all P<0.05). The predictive model was built by including the number of surgeries, surgical methods, breast milk, prenatal examination, nutrition and labor intensity during pregnancy into the predictive scoring system. The critical value was 273, the area under ROC curve (AUC) was 0.733(95%CI:0.704~0.76), the sensitivity was 89.57%, and the specificity was 48.14%.When the external validation data of 110 patients were brought into the score, the AUC of poor diagnostic value reached 74.5%, P<0.05, which was close to the modeling accuracy of 73.3%.
This study constructed a predictive model of surgical effect for patients with cleft lip and palate, which can be used for the clinical prediction of cleft lip and palate patients in Guizhou Province.
Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein ...convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated.
To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients.
The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography.
Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins.
The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated.
Among the 968 treated patients (mean age, 59.8 years SD, 9.2; 269 27.8% women; mean LDL-C level, 92.5 mg/dL SD, 27.2), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL; difference, -56.5 mg/dL 95% CI, -59.7 to -53.4; P < .001). The primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with evolocumab (difference, -1.0% 95% CI, -1.8% to -0.64%; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 95% CI, -7.3 to -2.5; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference, 17.0% 95% CI, 10.4% to 23.6%; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5% 95% CI, 5.9% to 19.2%; P < .001 for TAV).
Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes.
clinicaltrials.gov Identifier: NCT01813422.
Bearing faults are one kind of primary failure in rotatory machines. To avoid economic loss and casualties, it is important to diagnose bearing faults accurately. Vibration-based monitoring ...technology is widely used to detect bearing faults. Graph signal processing methods promising for the extraction of the fault features of bearings. In this work, graph multi-scale permutation entropy (MPE
) is proposed for bearing fault diagnosis. In the proposed method, the vibration signal is first transformed into a visibility graph. Secondly, a graph coarsening method is used to generate coarse graphs with different reduced sizes. Thirdly, the graph's permutation entropy is calculated to obtain bearing fault features. Finally, a support vector machine (SVM) is applied for fault feature classification. To verify the effectiveness of the proposed method, open-source and laboratory data are used to compare conventional entropies and other graph entropies. Experimental results show that the proposed method has higher accuracy and better robustness and de-noising ability.
•A novel three-stage division method for ecological transformation is proposed.•Comprehensively evaluated the performance of MRC ecological transformation.•Revealing the spatiotemporal heterogeneity ...of MRC ecological transformation.•Provide suggestions for the ecological transformation of MRCs in developing countries.
Ecological transformation is important for the sustainable development of China's Mineral Resource-based Cities (MRCs). The ecological transformation performance evaluation will help improve the accuracy and pertinence of transformation policy formulation. Based on the innovative division of ecological transformation stages of MRCs (transformation restoration, transformation adjustment, and transformation innovation periods), this empirical study takes 109 MRCs in China as the object and 2013–2019 as the time window and constructs the corresponding evaluation index system of China's MRC ecological transformation and the evaluation model of Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and Exploratory Spatial Data Analysis methods (ESDA) based on the Rough Set-Entropy Weight method. First, our results show that the ecological transformation performance of China's MRCs was poor. By 2019, 98% of the cities were in the adjustment stage. The transformation performance of cities with different resource types differed; from high to low, they were oil cities, ferrous metal cities, coal cities, and non-ferrous metal cities. Second, in terms of time, from 2013 to 2019, China's MRC ecological transformation performance showed a trend of first rising and then slightly fluctuating (from 0.3339 to 0.4158), of which the largest and smallest increases were the oil city (0.09) and black metal city (0.0803), respectively; Third, in terms of space, the ecological transformation of MRC in China had obvious spatial heterogeneity, spatial autocorrelation, and aggregation effect. On this basis, relevant policies such as dynamic monitoring, identification of transformation stage and regional cooperation are put forward. This study effectively expands the research on the ecological transformation of China's MRC and provided evidence for the precise formulation of relevant policies. It also provides a new perspective for the ecological transformation research of MRCs in other developing countries.
Multiple sclerosis is a severe brain and/or spinal cord disease. It may lead to a wide range of symptoms. Hence, the early diagnosis and treatment is quite important.
This study proposed a 14-layer ...convolutional neural network, combined with three advanced techniques: batch normalization, dropout, and stochastic pooling. The output of the stochastic pooling was obtained via sampling from a multinomial distribution formed from the activations of each pooling region. In addition, we used data augmentation method to enhance the training set. In total 10 runs were implemented with the hold-out randomly set for each run.
The results showed that our 14-layer CNN secured a sensitivity of 98.77 ± 0.35%, a specificity of 98.76 ± 0.58%, and an accuracy of 98.77 ± 0.39%.
Our results were compared with CNN using maximum pooling and average pooling. The comparison shows stochastic pooling gives better performance than other two pooling methods. Furthermore, we compared our proposed method with six state-of-the-art approaches, including five traditional artificial intelligence methods and one deep learning method. The comparison shows our method is superior to all other six state-of-the-art approaches.
Mental health literacy is considered an important factor in promoting professional psychological help-seeking attitudes. However, it is important to clarify the emotional and behavioral factors that ...underlie this association. Drawing from the ABC model of attitudes and the Health Disclosure Decision-Making Model, this study aimed to examine the mediating role of psychological help-seeking stigma and distress disclosure in the relationship between mental health literacy and professional psychological help-seeking attitudes.
We collected data from 827 participants in seven regions of China (597 female; M
= 26.019, SD = 5.592 years old) using self-report measures, including the Mental Health Literacy Scale, Questionnaire of Stigma for Seeking Professional Psychological Help, Distress Disclosure Index, and Attitudes Toward Seeking Professional Psychological Help-Short Form. A chain mediation model was built to examine the relationships among mental health literacy, psychological help-seeking stigma, distress disclosure, and professional psychological help-seeking attitudes.
The results of the analyses showed a positive association between mental health literacy and professional psychological help-seeking attitudes, with psychological help-seeking stigma and distress disclosure playing mediating roles in this relationship. Furthermore, even after controlling for participants' age, gender, and education, the chain mediation effect of psychological help-seeking stigma and distress disclosure on the relationship between mental health literacy and professional psychological help-seeking attitudes was observed among the Chinese population.
These findings underscore the significance of mental health literacy in shaping professional psychological help-seeking attitudes, while emphasizing the need to account for psychological help-seeking stigma and distress disclosure when examining this association. Additionally, the model proposed in this study provides a valuable framework for promoting the utilization of professional mental health services.
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