Adaptive group sequential design for phase II clinical trials: A Bayesian decision theoretic approach

Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd.     

氟比洛芬酯用于抑制神经外科气管拔管期不良反应的观察

目的探讨氟比洛芬酯用于抑制神经外科术后气管拔管期不良反应的有效性和可行性。方法ASAⅠ～Ⅱ级神经外科手术患者56例,随机分为观察组（氟比洛芬酯组）和对照组,2组分别在停用麻醉药前30min静注氟比洛芬酯注射液1.5mg/kg和加生理盐水5ml。在围拔管期观察并记录血压、心率、血氧饱和度、拔管时间、呼唤睁眼时间、躁动呛咳发生情况以及Ramsay镇静评分、VAS疼痛程度评分。结果围拔管期观察组的血压、心率均明显低于对照组,躁动和呛咳发生例数少,清醒度镇痛度明显优于对照组（P〈0.05）。结论氟比洛芬酯用于神经外科围拔管期可减轻气管拔管期不良反应,同时可产生良好的镇痛作用并维持满意的镇静度。     

Phase-sensitive cardiac tagging--REALTAG.

Fully inverting spins, instead of merely saturating them, provides superior contrast for tagging procedures. The resulting improvement in tag contrast-to-noise ratio (CNR) yields higher-precision tag detection. Also, thinner slices and hence reduced tag separations can be employed, providing displacement and strain measurements with better spatial resolution. Alternatively, the improved tag contrast can be used to obtain cine images covering a greater portion of the cardiac cycle. The use of standard magnitude reconstruction for images of these inversion tags causes rectification of the negative-valued signals from the tags, confounding the image interpretation. Therefore, a phase-sensitive reconstruction scheme of the inverted tags must be employed. Here we demonstrate the implementation of inverted tags with phase-sensitive reconstruction in a ramped-flip-angle, steady-state free precession (SSFP) sequence.     

Adiabatic refocusing pulses for volume selection in magnetic resonance spectroscopic imaging.

Because of their excellent slice profiles and high immunity to RF inhomogeneity, adiabatic full passage (AFP) pulses are ideal for use in spatial localization. The nonlinear, position-dependent phase of a single AFP pulse generated during refocusing of transverse magnetization traditionally is eliminated by using identical pairs of AFP pulses, at the expense of increased RF power deposition and increased echo time (TE). Here it is shown that one can achieve significant phase refocusing by executing single AFP pulses along non-equivalent spatial axes. When used for volume selection in MR spectroscopic imaging (MRSI) the remaining nonlinear phase becomes inconsequential when the phase across a spectroscopic volume is small. Selection of rectangular and octagonal volumes is demonstrated with half the number of AFP pulses used in the traditional approach. It is shown that octagonal volume selection in the human brain provides excellent suppression of extracranial lipids, and thus allows multislice (1)H MRSI at 4 Tesla to be performed within the guidelines for RF power deposition.     

Clinical influence of vagotomy on postoperative acute phase response

BACKGROUND: Although there is increasing evidence suggesting that the vagus nerve functions as a connector between the nervous and immune systems in animals, little is known about the role of the vagus nerve in postoperative acute phase response in humans. MATERIALS AND METHODS: The extent of fever and acute phase protein response and the production of inflammatory cytokine during the early postoperative period were compared among the patients who had undergone total gastrectomy including truncal vagotomy (n = 13), those having distal gastrectomy with division of vagal branches (n = 14), and the patients with vagal nerve preserving gastrectomy (n = 12). RESULTS: There was no significant difference in serum levels of C-reactive protein, alpha-1-antirypsin, and interleukin-6 among the three groups. Also, postoperative maximum body temperature was similar. CONCLUSIONS: Vagotomy did not influence acute phase response after gastric cancer surgery. A multipathway mechanism for acute phase response including the induction of fever is suggested.     

MR流量测定的实验研究

目的探讨MR流量测量与不同感兴趣区(ROI)直径的关系。方法使用Philips 1.5T双梯磁共振机流量测定程序,测量2mm内径塑胶管中不同流量的水(0.5、1.0、1.5、2.0、2.5ml/s),不同流向(流入及流出方向)、不同ROI位置(测量图中心区和偏中心区)与不同的ROI直径(直径0.5、1.0、1.5、2.0mm)流量变化关系,统计计算标准的ROI直径。结果在不同流量、流向和测量位置中,流量与ROI直径大小存在明显的直线相关(r>0.95,P<0.05),ROI直径大小显著地影响测量结果,当ROI直径取值等于测量图直径的0.6040±0.0480时,所测结果与实际流量一致。在不同流量下的不同流向及ROI位置对流量测定无影响(P>0.05)。结论对直径2mm流量测定,应选取测量图上直径的0.6040±0.0480 ROI进行。     

Three-dimensional magnetic resonance myocardial motion tracking from a single image plane.

Three-dimensional imaging for the quantification of myocardial motion is a key step in the evaluation of cardiac disease. A tagged magnetic resonance imaging method that automatically tracks myocardial displacement in three dimensions is presented. Unlike other techniques, this method tracks both in-plane and through-plane motion from a single image plane without affecting the duration of image acquisition. A small z-encoding gradient is subsequently added to the refocusing lobe of the slice-selection gradient pulse in a slice following CSPAMM acquisition. An opposite polarity z-encoding gradient is added to the orthogonal tag direction. The additional z-gradients encode the instantaneous through plane position of the slice. The vertical and horizontal tags are used to resolve in-plane motion, while the added z-gradients is used to resolve through-plane motion. Postprocessing automatically decodes the acquired data and tracks the three-dimensional displacement of every material point within the image plane for each cine frame. Experiments include both a phantom and in vivo human validation. These studies demonstrate that the simultaneous extraction of both in-plane and through-plane displacements and pathlines from tagged images is achievable. This capability should open up new avenues for the automatic quantification of cardiac motion and strain for scientific and clinical purposes.     

Neurophysiological aspects of chronic motor cortex stimulation

Chronic motor cortex stimulation is a treatment option for neuropathic drug-resistant pain and possibly associated movement disorders. Preliminary studies suggest the possibility to treat symptoms of Parkinson disease in selected patients. Recently, MCS has been suggested to enhance motor recovery in patients with poststroke hemiparesis. One or more electrodes are placed extradurally over the motor cortex through a burr hole or a small craniotomy, and then connected to a totally implantable neurostimulator. The accurate positioning of the stimulating electrodes over the motor cortex is the key point of the surgical procedure. Motor cortex identification results from the integration of anatomical, neuroradiological, functional, and neurophysiological data, taking into account the huge population variability. Intraoperative neurophysiological mapping of the motor cortex is of paramount importance, in spite of very sophisticated neuroradiological mathematical reconstructions of the motor area. We discuss and compare the different techniques that are utilized by different authors. Moreover, clinical neurophysiology is also helpful in evaluating the results of this neuromodulation procedure and in hypothesizing the mechanisms that are put in play by MCS.     

多层界面液膜的研究

经过对多层界面液膜的实验探索,获得了四相物系双层界面液膜和五相物系三层界面液膜等一系列多层界面液膜。并且提出了多层界面液膜自动形成的一般式,由此,展示了多层界面液膜的广阔领域。其中每一种多层界面液膜在应用上都将有其广泛的发展前景。