One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

邻近皮瓣修复面部皮肤缺损

目的 探讨邻近皮瓣修复面部皮肤缺损的应用效果。方法 162例面部病变切除后皮肤缺损患者，其中先天性色素痣63例，基底细胞癌28例，鳞状细胞癌6例，其他皮肤病变65例。均采用邻近皮瓣即时修复，其中菱形皮瓣57例、双叶皮瓣8例，A-T皮瓣23例、V-Y皮瓣13例、Z成形术23例、推进皮瓣27例、鼻状皮瓣11例。结果 162例皮瓣存活良好，手术切口1期愈合，存活后皮瓣颜色与邻近部位无明显差异，术后无眼睑、眉毛、鼻梁及口角牵扯歪钭，术后3个月切口不显露。结论 邻近皮瓣是修复面部较大皮肤缺损的良好方法，手术外观效果好。     

128例双胎妊娠临床结局分析

目的 :探讨影响双胎妊娠临床结局的相关因素。方法 :回顾性分析 12 8例双胎妊娠临床结局与胎方位、分娩方式、孕周、新生儿体重、新生儿窒息之间的关系。 结果 :胎方位、孕周、胎儿体重及分娩方式均影响围产儿预后。 结论 :加强孕产期保健 ,提高产科质量能改善双胎妊娠围产儿的预后。     

Surgical strategy of one stage surgery of anterior release combined with posterior correction in treatment of severe scoliosis

Objective: Severe scoliosis refers to scoliosis with serious and stiff curve. It always combins with trunk imbalance in coronal and sagittal contour. Besides complex pathological changes, cardiopulmonary deficits and other concomitant diseases increase treatmental difficulties. So the treatment of severe scoliosis is always a great challenge to spine surgeon. Methods :Thirty-six patients with severe scoliosis received one stage posterior correction followed by anterior release during July 1997 to January 2003, including 9 males and 27 females. Mean age was 17.2 years. Of them, 33 was idiopathic scoliosis and 3 was neurofibromatosis scoliosis( Cobb angle: 85-116 degree); 20 cases were abnormal in sagital plane. Three-dimensional devised instrumentation were applied such as CD, CD-Horizon, TSRH or Isola in posterior procedure followed by anterior release during the same anesthesia. 31 cases of this group received thorac icplasty. Results: The correction in the frontal plane achieved an average of 48.5%. In the sagittal plane, the pathological shape of the spine was reduced and distinctly ameliorated. 80. 6% of the patients maintained or achieved balance of sagittal plane. There were no complications of severe neurological deficit, hook displacement, rod broken, and deep infection at follow-up. One case occurred traumatic pleurisy after operation and another appeared pseudarthrosis 2 years later. One case demonstrated imbalance 11 months after operation. One patient was presented loss of correction more than 10 degree at one year follow-up and 5.2 degree in average. Conclusion:The study indicates that the one stage posterior correction combined with anterior release in treatment of severe scoliosis can achieve satisfactory correction. Appropriate choice of cases, preoperational detailed assessment and application of SEP and wake-up test during operation can possibly reduce severe complication. The long-term outcomes still need further observation.     

An Innovative Approach to Chairside Provisional Replacement of an Extracted Anterior Tooth: Use of Fiber-Reinforced Ribbon-Composites and a Natural Tooth

Immediate chairside replacement of an extracted anterior tooth may contribute to a patient's comfort, treatment acceptance, and expectations of treatment; however, fabrication of a custom restoration in the anterior region of the mouth may result in an esthetic compromise for patients during the fabrication period. Chairside tooth replacement is an excellent application of fiber-reinforced composite resin technology. This article presents an innovative, affordable chairside procedure in which Ribbond Multi-Purpose Bondable Reinforcement Ribbon is used to replace a single extracted anterior tooth using the patient's own tooth.     

1 108例终末期肾脏疾病血液透析病人原发疾病构成及相关因素分析

目的 回顾性研究终末期肾脏疾病（end stage renal disease，ESRD）血液透析病人原发疾病构成及其相关因素。方法 收集ESRD血液透析病人1108例，分析其原发疾病构成、年龄、性别、透析治疗持续时间、转归、生存率和死亡原因。结果 301例病人透析时间超过3个月，其中43．9％仍在进行血液透析治疗，最长者已存活13年；13．0％病人已行肾脏移植；19．9％转至外院治疗；7．3％改为腹膜透析；1．3％因经济困难放弃治疗；14．6％病人死亡。ESRD维持性血液透析病人1年生存率为93．53％，3年生存率为68．92％。5年生存率62．51％。死亡原因为心血管事件占54．5％，脑血管意外占20．5％。结论 本组病人以中、老年为主，男性多见。ESRD血液透析病人主要原发疾病为慢性肾小球肾炎，主要死亡原因为心血管事件和脑血管意外。     

New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma

Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast-enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post-treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non-invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real-time imaging of multi-detector CT and US, known as real-time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients.     

Detailed Analysis of Mucosal Restoration of the Small Intestine After the Cavitary Two-Layer Cold Storage Method

Small bowel transplantation (SBT) is associated with a high incidence of infectious complications because of ischemia/reperfusion (I/R) mucosal injury concomitant with potent immunosuppression. In this study, we evaluated whether the cavitary two-layer method (cTLM) could reduce I/R injury and allow early mucosal restoration, particularly after prolonged preservation and transplantation. Canine heterotopic segmental SBT was performed immediately without preservation (group 1), after 24-h preservation in UW solution (group 2) or by the cTLM (group 3). The graft samples were taken 1 h after reperfusion and on days 1, 4 and 7. We assessed graft mucosa with detailed microscopic and electromicroscopic analyses. In Group 3, histological injury and cell apoptosis after transplantation were significantly alleviated and rapidly recovered to a similar level of group 1. The mucosal restoration was morphologically completed within 4 days. In contrast, in group 2, more pronounced mucosal injury and delayed recovery were noted. Crypt cell proliferation activity was well maintained in groups 1 and 3 throughout the experimental period. Our ultrastructural analysis suggested that mitochondrial integrity achieved by the cTLM was a basal mechanism under the prompt mucosal restoration. The cTLM could reduce I/R injury, facilitate mucosal regeneration and restore the nearly normal structure early after SBT.     

Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.

BACKGROUND: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis. AIMS/METHODS: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss). RESULTS: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome. CONCLUSION: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.     

An improved method of flexible endoscopic creation of tracheoesophageal fistula for voice restoration

We present improvements of a previously reported method of tracheoesophageal puncture for voice restoration in postlaryngectomy patients. Our method utilizes a flexible endoscope to enable the tracheoesophageal puncture to be made under direct visualization using only local anesthesia and intravenous sedation. After 3 days, the created tracheoesophageal fistula tract is mature enough to allow placement of a voice prosthesis in the office. This allows the entire procedure to be performed in an outpatient setting with minimal risk. Received: 24 October 1996/Accepted: 24 January 1997