435例原发性高血压患者脉图参数与心血管危险分层的相关性分析

目的 本研究旨在探讨原发性高血压患者脉图参数与心血管危险分层的相关性，为原发性高血压患者心血管风险事件预警提供中医特色的依据。方法 采集435例原发性高血压患者的症状体征、脉象信息、生化指标等，分为低中危组、高危组、很高危组，采用单因素方差分析、秩和检验、有序logistic回归分析等方法，探讨原发性高血压患者脉图参数与心血管危险分层的相关性。结果 ①高血压低中危组→高危组→很高危组患者病程逐渐延长，两两组间比较有统计学差异；②高血压低中危组→高危组→很高危组患者的脉图参数H3/H1、H4/H1逐渐上升；高血压患者很高危组H5/H1、T1/T低于低中危组；③有序logistic回归分析结果显示，脉图参数T1、T4、T5、T为影响因素。结论 病程、血脂、肾功能是高血压患者心血管危险分层的影响因素之一。心血管危险分层等级的升高与脉图参数H3/H1、H4/H1、T5、T的升高及H5/H1、T4、T1的降低相关，说明脉图能一定程度上反映原发性高血压患者血管壁增厚、血管内壁受损、血管硬化及左心室收缩功能的减退程度。     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

The price of cost-effectiveness thresholds under therapeutic competition in pharmaceutical markets

Health systems around world are increasingly adopting cost-effectiveness (CE) analysis to inform decisions about access and reimbursement. We study how CE thresholds imposed by a health plan for granting reimbursement affect drug producers’ pricing incentives and patients’ access to new drugs. Analysing a sequential pricing game between an incumbent drug producer and a potential entrant with a new drug, we show that CE thresholds may have adverse effects for payers and patients. A stricter CE threshold may induce the incumbent to switch pricing strategy from entry accommodation to entry deterrence, limiting patients’ access to the new drug. Otherwise, irrespective of whether entry is deterred or accommodated, a stricter CE threshold is never pro-competitive and may in fact facilitate a collusive outcome with higher prices of both drugs. Compared to a laissez-faire policy, the use of CE thresholds when an incumbent monopolist is challenged by therapeutic substitutes can only increase the surplus of a health plan if it leads to entry deterrence. In this case the price reduction by the incumbent necessary to deter entry outweighs the health loss to patients who do not get access to the new drug.     

Effects of the Cerebral Aneurysm Treatment Method on Coil Packing Density and Its Relationship with the Ostium Area

PurposeTo test the following hypotheses: (a) balloon or stent assistance increases coil packing density (CPD) in the endovascular treatment of intracranial aneurysms, and (b) CPD correlates to ostium area (OA) and aneurysm volume (AV).Materials and MethodsThis retrospective study included 60 aneurysms (54 ruptured and 6 unruptured) treated with simple coiling (SC) (n = 18), balloon-assisted coiling (BAC) (n = 7), or stent-assisted coiling (SAC) (n = 35) at the authors’ institution between August 2017 and December 2019. AV and OA measurements were obtained from 3-dimensional digital subtraction angiography images using commercial software. Coil sizes were retrieved from patient files, and coil volume (CV) measurements were obtained from https://www.angiocalc.com/. Analysis of covariance, multivariate covariance analysis, and Pearson correlation analyses were performed.ResultsThe median value for AV, CV, CPD, and OA was 63.4 mm³ (range, 5.5–1,771.4 mm³), 23.13 mm³ (range, 2.03–296.95 mm³), 33.29% (range, 13.41%–81.02%), and 10.7 mm² (range, 2.7–49.9 mm²), respectively. Multivariate analysis showed that the CPD values were not significantly different among the treatment groups, although OA significantly differed between the SC and SAC groups (P < .05). Pearson correlations showed that similar to AV, OA was negatively correlated with CPD (r = ?0.321, P < .05).ConclusionsThe CPD value in cerebral aneurysms treated with BAC or SAC did not differ from that in aneurysms treated with SC.     

Assessment of a novel deep learning-based marker-less motion capture system for gait study

BackgroundMarker-less systems based on digital video cameras and deep learning for gait analysis could have a deep impact in clinical routine. A recently developed system has shown promising results in terms of joint center position but has not been yet evaluated in terms of gait outcomes.Research questionHow does this novel marker-less system compare to a marker-based reference system in terms of clinically relevant gait parameters?MethodsThe deep learning method behind the developed marker-less system was trained on a dedicated dataset consisting of forty-one asymptomatic and pathological subjects each performing ten walking trials. The system could estimate the three-dimensional position of seventeen joint centers or keypoints (e.g., neck, shoulders, hip, knee, and ankles). We evaluated the marker-less system against a marker-based system in terms of differences in joint position (Euclidean distance), detection of gait events (e.g., heel strike and toe-off), spatiotemporal parameters (e.g., step length, time), kinematic parameters (e.g., hip and knee extension-flexion), and inter-trial reliability for kinematic parameters.ResultsThe marker-less system was able to estimate the three-dimensional position of joint centers with a mean difference of 13.1 mm (SD = 10.2 mm). 99% of the estimated gait events were estimated within 10 ms of the corresponding reference values. Estimated spatiotemporal parameters showed zero bias. The mean and standard deviation of the differences of the estimated kinematic parameters varied by parameter (for example, the mean and standard deviation for knee extension flexion angle were −3.0° and 2.7°). Inter-trial reliability of the measured parameters was similar to that of the marker-based references.SignificanceThe developed marker-less system can measure the spatiotemporal parameters within the range of the minimum detectable changes obtained using the marker-based reference system. Moreover, except for hip extension flexion, the system showed promising results in terms of several kinematic parameters.     

Updated Trends,Disparities, and Clinical Impact of Neuroimaging Utilization in Ischemic Stroke in the Medicare Population: 2012 to 2019

ObjectiveThe purpose of this study was to update trends, investigate sociodemographic disparities, and evaluate the impact on mortality of stroke neuroimaging across the United States from 2012 to 2019.MethodsRetrospective cohort study using CMS Medicare 5% Research Identifiable Files, representing consecutive ischemic stroke emergency department or hospitalized patients aged ≥65 years. A total of 85,547 stroke episodes with demographic and clinical information were analyzed using Cochran-Mantel-Haenszel tests and logistic regression. Outcome measures were neuroimaging (CT angiography [CTA], CT perfusion [CTP], MRI, MR angiography [MRA]) utilization, acute treatment (endovascular thrombectomy [EVT] and intravenous thrombolysis [IVT]), and mortality while in the hospital and at 30 days and 1 year post discharge.ResultsSignificantly increasing utilization trends for CTA (250%), CTP (428%) and MRI (18%), and a decreasing trend for MRA (?33%) were observed from 2012 to 2019 (P < .0001). Controlling for covariates in the logistic regression models, CTA and CTP were significantly associated with higher EVT and IVT utilization. Although CTA, MRI, and MRA were associated with lower mortality, CTP was associated with higher mortality post discharge. Less neuroimaging was performed in rural patients; older patients (≥80 years) had lower utilization of CTA, MRI, and MRA; female patients had lower rates of CTA; and Black patients had lower utilization of CTA and CTP.ConclusionsCTA and CTP utilization increased in the Medicare ischemic stroke population from 2012 to 2019 and both were associated with greater EVT and IVT use. However, disparities exist in neuroimaging utilization across all demographic groups, and further understanding of the root causes of these disparities will be crucial to achieving equity in stroke care.     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

中青年楼宇人群的家庭医生签约服务需求满足状况及影响因素研究

背景 上海市正逐步将家庭医生签约服务拓展至楼宇功能社区，目前中青年楼宇人群的服务需求满足状况尚不知晓。研究中青年楼宇人群的家庭医生签约服务需求满足状况，分析其影响因素，可以为制定和调整家庭医生楼宇服务相关政策提供参考。 目的 探讨中青年楼宇人群的家庭医生签约服务需求满足状况，并分析其影响因素。 方法 于2019年12月至2020年12月，在上海市虹口区、浦东新区、静安区采用典型抽样法抽取楼宇，在选中楼宇内采用整群随机抽样法抽取中青年人群（18~59岁）开展问卷调查，共回收有效问卷2 272份，本研究以其中有家庭医生服务利用经历的1 137例受试者为研究对象。涉及的主要调查内容为受试者的社会人口和经济学特征、健康状况、对家庭医生签约服务的了解度及家庭医生签约服务需求满足状况（包括基本服务需求、个性化服务需求两方面，均采用Likert 5级评分法）。采用多元有序Logistic回归分析中青年楼宇人群家庭医生签约服务需求满足状况的影响因素。 结果 39.61%（425/1 073）的受试者表示家庭医生签约服务比较满足/完全满足其基本服务需求，39.01%（419/1 074）的受试者表示家庭医生签约服务比较满足/完全满足其个性化服务需求。多元有序Logistic回归分析结果显示：户籍、职业类别、年收入、自评健康状况、对家庭医生"1+1+1"签约服务了解度、对家庭医生信任度、对家庭医生服务能力评价是中青年楼宇人群基本服务需求满足状况的影响因素（P<0.05）；性别、年收入、患慢性病情况、对家庭医生"1+1+1"签约服务了解度、对家庭医生团队组成了解度、对家庭医生服务能力评价是中青年楼宇人群个性化服务需求满足状况的影响因素（P<0.05）。 结论 约40%的楼宇人群认为家庭医生签约服务能够满足其基本服务需求/个性化服务需求，主要影响因素可概括为楼宇人群的社会经济状况、健康状况、对家庭医生签约服务的认知度、家庭医生的服务能力4个方面。建议加强对家庭医生签约服务的宣传，并针对楼宇人群特点和差异化需求，为其定制个性化的服务方案；同时，着力提升家庭医生服务能力，丰富签约服务内涵。