中心随机化系统在临床试验中的应用

中心随机化系统可保证随机化的准确实施,并可与最小化法结合在一起用于临床试验,尤其是在中药临床试验和开放试验中。本文从受试者管理、药物管理和使用者管理三个方面介绍中心随机化系统在临床试验中的应用,并简单介绍最小化法的原理。

中心随机化系统在“芪参益气滴丸对心肌梗死二级预防的临床试验研究”项目中的应用

中心随机化系统实际上是临床试验实施过程中的管理系统,不但可以减少随机化过程中的人为参与,更好地避免偏倚,而且对于用药量大、研究周期较长的大规模临床试验的药品管理尤为重要。本文介绍了中心随机化系统的两个主要功能(即受试者随机化和药品管理),以及临床研究语音应答系统(CRIVRS)在芪参益气滴丸对心肌梗死二级预防的临床试验研究(MISPS-TCM)项目实施过程中的操作要点和注意事项。

最小随机化分组系统在多中心临床试验中的应用

最小随机化分组方法以其突出的组间例数和预后因素的均衡能力,受到越来越多新药临床试验研究人员的关注。但由于计算复杂,实施难度大,该方法一直未得到大规模推广应用。本研究结合自主开发的一套基于网络的最小随机化分组系统在随机对照双盲新药临床试验中的应用,讨论了该系统的优点和不足,希望能为同行提供借鉴,并促进最小随机化方法以及中心随机化系统在多中心新药临床试验中的应用。

基于GAMP5指南的临床试验中央随机化系统验证流程和实践

目的基于国际制药工程协会颁布的《自动化生产质量管理规范第5版》(GAMP5),结合国内外指导原则和法规要求,制定一套临床试验中央随机化系统验证的流程。方法依据GAMP5指南和国内外计算机化系统验证指导原则和法规,结合临床试验中央随机化系统自身特点,建立临床试验中央随机化系统的GAMP5验证流程及规范,以现有临床试验中央随机化系统为实例,展示验证结果。结果构建了符合临床试验相关法规要求的中央随机化系统验证框架和流程。以现有系统为实例,成立验证小组,制定验证计划,按照V模型进行计算机化系统验证,形成一套规范的验证文档。结论本研究所提出的中央随机化系统验证流程遵循GAMP5规范,具有较高的可操作性和参考价值。

结合实例的复方优选临床试验的随机化方案设计

目的介绍复方优选临床试验的随机化方案设计,并评价基于网络的中央随机系统(IWRS)对提高临床试验质量的作用。方法以一个研究实例,采用IWRS进行随机化方案设计,包括随机序列分配、随机隐藏、随机化药品发放以及随机化药品供应、随机隐藏下的电子应急信件。结果基于IWRS的随机化方案,可有效避免传统随机方式可能产生的选择性偏倚,更好地实施随机隐藏,保证随机化的准确性;同时可减少药品浪费,简化管理环节,降低研究成本。结论 IWRS可使随机化实施更为便捷,是提高临床试验质量和效率的重要措施之一,尤其对于大规模复杂的临床试验更是如此。

一类随机化TCP/RED系统的稳定性研究

研究构建了一类由白噪声驱动的随机化TCP/RED系统,利用随机微分理论和Lyapunov稳定性理论,通过构建Lyapunov函数得出的随机化TCP/RED系统在噪声环境下具有稳定性.本研究使用ns2网络仿真器进行仿真,结果表明,当参数满足一定条件时,证明了随机化TCP/RED模型的全局随机渐进稳定性.

Upper gastrointestinal endoscopy:Are preparatory interventions or conscious sedation effective? A randomized trial

AIM: The fears and concerns are associated with gastroscopy (EGD) decrease patient compliance. Conscious sedation (CS) and non-pharmacological interventions have been proposed to reduce anxiety and allow better execution of EGD. The aim of this study was to assess whether CS, supplementary information with a videotape, or presence of a relative during the examination could improve the tolerance to EGD. METHODS: Two hundred and twenty-six outpatients (pts), scheduled for a first-time non-emergency EGD were randomly assigned to 4 groups: Co-group (62 pts): throat anaesthesia only; Mi-group (52 pts): CS with i.v. midazolam; Re-group (58 pts): presence of a relative throughout the procedure; Vi-group (54 pts): additional information with a videotape. Anxiety was measured using the “Spielberger State and Trait Anxiety Scales” The patients assessed the overall discomfort during the procedure on an 100-mm visual analogue scale, and their tolerance to EGD answering a questionnaire. The endoscopist evaluated the technical difficulty of the examination and the tolerance of the patients on an 100-mm visual analogue scale and answering a questionnaire. RESULTS: Pre-endoscopy anxiety levels were higher in the Mi-group than in the other groups (P<0.001). On the basis of the patients' evaluation, EGD was well tolerated by 80.7% of patients in Mi-group, 43.5% in Co-group, 58.6% in Regroup, and 50% in Vi-group (P<0.01). The discomfort caused by EGD, evaluated by either the endoscopist or the patients, was lower in Mi-group than in the other groups. The discomfort was correlated with “age” (P<0.001) and “groups of patients” (P<0.05) in the patients' evaluation, and with “gender” (females tolerated better than males, P<0.001) and “groups of patients” (P<0.05) in the endoscopist's evaluation. CONCLUSION: Conscious sedation can improve the tolerance to EGD. Male gender and young age are predictive factors of bad tolerance to the procedure.

Association of traditional Chinese exercises with glycemic responses in people with type 2 diabetes:A systematic review and meta-analysis of randomized controlled trials

Background： There is increasing evidence showing the health benefits of various forms of traditional Chinese exercises （TCEs） on the glycemic profile in people with type 2 diabetes. However, relatively little is known about the combined clinical effectiveness of these traditional exercises. This study was designed to perform a systematic review and meta-analysis of the overall effect of 3 common TCEs （Tai Ji Quan, Qigong, Ba Duan Jin） on glycemie control in adults with type 2 diabetes. Methods： We conducted an extensive database search in Cochrane Library, EMBASE, PubMed, Web of Science, EBSCO, and China National Knowledge Infrastructure on randomized controlled trials published between April 1967 and September 2017 that compared any of the 3 TCEs with a control or comparison group on glycemic control. Data extraction was performed by 2 independent reviewers. Study quality was evaluated using the Coehrane Handbook for Systematic Reviews of Interventions, which assessed the risk of bias, including sequence generation, allocation concealment, blinding, completeness of outcome data, and selective outcome reporting. The resulting quality of the reviewed studies was characterized in 3 grades representing the level of bias： low, unclear, and high. All analyses were performed using random effects models and heterogeneity was quantified. We a priori specified changes in biomarkers of hemoglobin A1 c （in percentage） and fasting blood glucose （mmol/L） as the main outcomes and triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein-cholesterol, 2-h plasma glucose, and fasting plasma glucose as secondary outcomes.Results： A total of 39 randomized, controlled trials （Tai Ji Quan = 11; Qigong= 6; Ba Duan Jin= 22） with 2917 type 2 diabetic patients （aged 41-80 years） were identified. Compared with a control or comparison group, pooled meta-analyses of TCEs showed a significant decrease in hemoglobin Alc （mean difference （MD）= -0.67%; 95% confidence interval （CI）：-0.86% to-0.48%; p 〈 0.00001） and fasting blood glucose （MD = -0.66 mmol/L; 95%CI： -0.95 to -0.37 mmol/L; p 〈 0.0001）. The observed effect was more pronounced for interventions that were medium range in duration （i.e., 〉3-〈 12 months）. TCE interventions also showed improvements in the secondary outcome measures. A high risk of bias was observed in the areas of blinding （i.e., study participants and personnel, and outcome assessment）. Conclusion： Among patients with type 2 diabetes, TCEs were associated with significantly lower hemoglobin Alc and fasting blood glucose. Further studies to better understand the dose and duration of exposure to TCEs are warranted.2018 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//creativecommons.org/licenses/by-nc-nd/4.0/）.

Synchronization of hyperchaotic Rossler system with uncertain parameters via nonlinear control

Based on the Lyapunov stability theory,a new method for synchronization of hyperchaotic Rossler system with uncertain parameters is proposed. By this method, choosing appropriate control law and adaptive update law of uncertain parameters, all the errors of system variable synchronization and of uncertain param- eter track are asymptotically stable. The theoretical analysis and the numerical simulations prove the efffectiveness of the oroDosed method.

Efficient Stochastic Simulation Algorithm for Chemically Reacting Systems Based on Support Vector Regression

The stochastic simulation algorithm （SSA） accurately depicts spatially homogeneous wellstirred chemically reacting systems with small populations of chemical species and properly represents noise, but it is often abandoned when modeling larger systems because of its computational complexity. In this work, a twin support vector regression based stochastic simulations algorithm （TS^3A） is proposed by combining the twin support vector regression and SSA, the former is a well-known robust regression method in machine learning. Numerical results indicate that this proposed algorithm can be applied to a wide range of chemically reacting systems and obtain significant improvements on efficiency and accuracy with fewer simulating runs over the existing methods.

Extended Jacobi Elliptic Function Rational Expansion Method and Its Application to （2＋1）-Dimensional Stochastic Dispersive Long Wave System

In this work, by means of a generalized method and symbolic computation, we extend the Jacobi elliptic function rational expansion method to uniformly construct a series of stochastic wave solutions for stochastic evolution equations. To illustrate the effectiveness of our method, we take the （2＋ 1）-dimensional stochastic dispersive long wave system as an example. We not only have obtained some known solutions, but also have constructed some new rational formal stochastic Jacobi elliptic function solutions.

Telemonitoring and hemodynamic monitoring to reduce hospitalization rates in heart failure： a systematic review and meta-analysis of randomized controlled trials and real-world studies

Background Heart failure is a significant problem leading to repeated hospitalizations. Telemonitoring and hemodynamic monitoring have demonstrated success in reducing hospitalization rates, but not all studies reported significant effects. The aim of this systematic review and meta-analysis is to examine the effectiveness of telemonitoring and wireless hemodynamic monitoring devices in reducing hospitalizations in heart failure. Methods ＆ Results PubMed and Cochrane Library were searched up to 1st May 2017 for articles that investigated the effects of telemonitoring or hemodynamic monitoring on hospitalization rates in heart failure. In 31,501 patients （mean age： 68 ± 12 years; 61% male; follow-up 11 ± 8 months）, telemonitoring reduced hospitalization rates with a HR of 0.73 （95% CI： 0.65-0.83; P 〈 0.0001） with significant heterogeneity （I2 = 94%）. These effects were observed in the short-term （≤ 6 months： HR = 0.77, 95% CI： 0.65-0.89; P 〈 0.01） and long-term （≥ 12 months： HR = 0.73, 95% CI： 0.62-0.87; P 〈 0.0001）. In 4831 patients （mean age 66 ± 18 years; 66% male; follow-up 13 ± 4 months）, wireless hemodynamic monitoring also reduced hospitalization rates with a HR of 0.60 （95% CI： 0.53-0.69; P 〈 0.001） with significant heterogeneity （I2 = 64%）.This reduction was observed both in the short-term （HR = 0.55, 95% CI： 0.45-0.68; P 〈 0.001; I2 = 72%） and long-term （HR = 0.64, 95% CI： 0.57-0.72; P 〈 0.001; I2 = 55%）. Conclusions Telemonitoring and hemodynamic monitoring reduce hospitalization in both short- and long-term in heart failure patients

Land-Cover Change Monitoring in Obuasi, Ghana： An Integration of Earth Observation, Geoinformation Systems and Stochastic Modelling

For over twenty years, Obuasi Municipality, Ghana, has experienced land-cover change arising from gold mining and urbanisation. This project quantified the land-cover changes that have taken place and projected likely future land-cover. An integration of EO （earth observation）, GIS （geographical information science） and Stochastic Modelling was examined. Post-classification Change Detection employed Landsat TM or ETM＋ images in 1986, 2002 and 2008. Subsequently, Markov Chain Analysis projected the land-cover distribution for 2020. Seven broad land-use and land-cover classes were identified and mapped, namely： built-up areas, mine sites tailing ponds barren land forestland farmland and rangeland. The results obtained for the 2008 to 2020 projection revealed a continuous expansion of built-up areas （1.63%）, mine sites （0.89%） and farmland （3.4%）, and a reduction of forestland （4.17%） and rangeland （2.59%）. Despite the advent of very high resolution satellite imagery, this use of EO and GIS technology focussed on low-cost and lower resolution satellite imagery, coupled with Markov Modelling and was found to be beneficial in describing and analysing land-cover change processes in the study area, and was hence potentially useful for strategic planning purposes.

Polarization Projection for 3D Geometry-Based Stochastic Channel Model

Comprehensive radiation characteristics of polarized antenna are crucial in creating practical channel coefficients for next generation wireless communication system designs.Being currently supported within3 D geometry-based stochastic channel models(GSCM),field patterns are technically obtained by chamber measurement(or by its best fitting).However,in some channel related performance analysis scenarios,design insight can be crystallized better by starting the derivations with theoretical co-polarization and cross-polarization components.Specifically,these two components are mathematically linked with field patterns through the proposed polarization projection algorithm.In this manuscript,we focus on revealing the transformation criterion of polarization states between the antenna plane and the propagation plane.In practice,it makes retrieving the field patterns by electromagnetic computation possible.Meanwhile,the impact imposed by distinct antenna orientations is geometrically illustrated and consequently incorporated into the proposed algorithm.This will further facilitate flexible performance evaluation of related radio transmission technologies.Our conclusions are verified by the closed-form expression of the dipole field pattern(via an analytical approach) and by chamber measurement results.Moreover,we find that its 2D degenerative case is aligned with the definitions in 3^(rd) generation partnership project(3GPP)technical report 25.996.The most obvious benefit of the proposed algorithm is to significantly reduce the cost on generating channel coefficients in GSCM simulation.

Systematic Review of Acupuncture for Functional Constipation

Objective： To systematically analyze the therapeutic efficacy and safety of acupuncture in treating functional constipation （FC）. Methods： By searching the Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, WanFang databases, the randomized controlled trials （RCTs） comparing acupuncture with Western medication in treating FC were retrieved, from the inception of the databases to September 2013. When the literatures were arranged according to the inclusion and exclusion criteria, and the methodological qualities were evaluated, RevMan 5.2 was adopted for meta-analysis. Results： Ten RCTs were included, covering 1 041 cases of FC. The meta-analysis showed that there was no significant difference in comparing spontaneous bowel movements per week between shallow acupuncture at Tianshu （ST 25） and Western medication [MD=0.47, 95% CI （-1.28, 0.34）]; there was a significant difference in comparing the spontaneous bowel movements per week between deep acupuncture at Tianshu （ST 25） and Western medication [MD =0.53, 95% CI （0.13, 0.92）], but the difference was insignificant according to the sensitivity analysis [MD=0.38, 95% Cl （-0.03, 0.80）], indicating the low reliability of the conclusion. Regarding the Cleveland clinic score （CCS）, the difference between shallow acupuncture at Tianshu （ST 25） and Western medication was insignificant [MD = 0.39, 95% Cl （-1.13, 1.91）]; the difference between deep acupuncture at Tianshu （ST 25） and Western medication was significant [MD=2.64, 95% Cl （1.32, 3.97）]. In the evaluation of security, the incidence rate of adverse events in acupuncture treatment （0.31%） was significantly lower than that in Western medication treatment （3.4%）. Conclusion： Although the present systematic review showed that deep acupuncture at Tianshu （ST 25） should have better therapeutic efficacy than Western medication, the reliability and quality of the evidences were poor, and thus the above results require proving by more RCTs of higher quality.

Meta-analysis on randomized controlled trials for scalp acupuncture treatment of stroke：A systematic review

OBJECTIVE:To conduct a systematic review to assess the clinical effectiveness of scalp acupuncture(SA) for stroke.METHODS:Literature searches were performed in7 databases up to 16 August 2014,and all the randomized controlled trials(RCTs) in which SA therapy was administered to stroke patients were selected.Methodological quality was assessed using the Jadad score,the Cochrane risk of bias assessment,and the Standards for Reporting Interventions in Clinical Trials of Acupuncture.RESULTS:Of a total of 2086 papers,21 RCTs were selected.Meta-analysis revealed significant differences in the total efficacy rates of the SA group and the body acupuncture(BA) group vs the medication group(P < 0.002,P < 0.000 001,respectively),the SA plus BA group vs the BA group(P < 0.001);in the motor function of the SA plus BA group vs the BA group(P = 0.077);and in the nerve function of the SA group vs the SA plus BA group(P < 0.0001).CONCLUSION:The results of our systematic review showed that SA therapy may exhibit effects in treatment efficacy and in the recovery of motor and nervous functions in patients with acute to chronic stroke.However,because of the lack of methodological quality,the thoroughly planned clinical studies are still required.

Traditional Chinese Medicine for the treatment of influenza: a systematic review and Meta-analysis of randomized controlled trials

OBJECTIVE: To justify the clinical use of Traditional Chinese Medicine(TCM) in the treatment of influenza.METHODS: MEDLINE, EMBASE, Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wanfang Database and the Cochrane Database of Systematic Reviews were searched from thedate of inception until January 1,2013, for the literature on treatment of influenza with TCM.RESULTS: A total of 7 randomized controlled trials were identified and reviewed. Of these trials, 2 compared a(modified) prescription of TCM with oseltamivir and 5 compared a patent traditional Chinese drug with oseltamivir. Based on the Meta-analysis,compared to oseltamivir, the(modified) prescription had similar effect in defervescence [WMD=5.66, 95% CI(﹣32.02, 43.35), P=0.77] and viral shedding [WMD=﹣ 6.21, 95% CI(﹣84.19, 71.76), P=0.88], and the patent traditional Chinese drug also had similar effect in viral shedding [WMD=﹣ 0.24,95% CI(﹣4.79, 4.31), P=0.92] but more effective in defervescence [WMD=﹣4.65, 95%CI(﹣8.91, ﹣0.38),P=0.03].CONCLUSION: TCM has potential positive effects in the treatment of influenza.