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.     

糖尿病肾内动脉血流动力学改变的研究

目的：观察糖尿病肾病不同时期肾内分级动脉血流动力学的改变。方法：用脉冲多普勒方法分别测量正常对照组、糖尿病正常蛋白尿阶段，隐匿性肾病．临床糖尿病肾病肾功能代偿期及糖尿病肾病肾功失代偿期各组肾内分级动脉Vmax、Vmin、TAMX、PI、RI血流参数．并与对照组比较。结果：糖尿病不同时期Vmax均增高．与正常对照组有显著性差异；Vmin随着病程的发展．逐渐减低；PI、RI随病情的进展逐渐增高．尤以糖尿病肾病肾功能代偿期及肾病肾功失代偿期明显。结论：多普勒超声是一种简便、直观、快速非创伤性检查糖尿病血流动力学改变的方法．通过对肾内分级动脉血流参数的观察．尤其是PI、RI的变化，判断糖尿病肾损害的程度。     

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。     

枸杞果柄对四氧嘧啶糖尿病小鼠血糖的影响

目的 探讨枸杞果柄水煎剂对四氧嘧啶糖尿病小鼠血糖的影响.方法 制备四氧嘧啶糖尿病小鼠模型,将其分为降糖灵治疗组、低剂量枸杞果柄治疗组、高剂量枸杞果柄治疗组、模型对照组,另设正常对照组(非糖尿病小鼠).前3组小鼠分别以25 mg·kg-1·d-1降糖灵水溶液、5.0 g·kg-1·d-1枸杞果柄水煎剂、7.5 g·kg-1·d-1枸杞果柄水煎剂灌胃,后2组小鼠均灌服等量的生理盐水.14 d后测定小鼠空腹血糖.结果 给药14 d后降糖灵治疗组、低剂量枸杞果柄治疗组小鼠血糖较治疗前有极显著下降(P<0.01),高剂量枸杞果柄治疗组小鼠血糖较治疗前有显著下降(P<0.05);降糖灵治疗组、不同剂量枸杞果柄治疗组血糖降低平均值与模型对照组、正常对照组血糖变化平均值之间均存在极显著差异(P<0.01).结论 一定剂量的枸杞果柄水煎剂对四氧嘧啶糖尿病小鼠血糖有降低作用.     

循环内皮细胞水平与糖尿病肾病的相关性及银杏达莫的干预作用

目的:探讨外周血循环内皮细胞(CEC)和糖尿病肾病(DN)的相关性,以及银杏达莫注射液在DN防治中的可能作用。方法:检测65例2型糖尿病患者24h尿白蛋白排泄率(UAER)及CEC数,分析两者的相关性。将UAER为30~300mg·d-1的45例患者随机分为两组,常规治疗组22例,进行常规降血糖、控制血压等治疗;银杏达莫治疗组23例,在常规治疗基础上静脉滴注银杏达莫注射液2周。比较两组治疗前后血糖、血压、UAER及CEC水平的变化。结果:单纯糖尿病(SDM)组和早期糖尿病肾病(EDN)组的外周血CEC水平比对照组(NC)显著性升高,并呈逐渐增高的趋势(P<0.01)。UAER与收缩压(SBP)、外周血CEC水平呈正相关(P<0.01)。EDN组中,银杏达莫治疗后UAER及CEC明显降低(P<0.01);而常规治疗组无明显变化。线性多元逐步回归分析表明,银杏达莫治疗后UAER的改变与CEC数的变化成正相关(P<0.01)。结论:血管内皮细胞(VEC)损伤在DN发生发展中起重要作用,银杏达莫对VEC的保护作用可能是其延缓DN发展的重要机制。     

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.     

Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome

We report clinical and pathological data in 56 adolescents presenting with gross hematuria (GH) and 65 presenting with idiopathic nephrotic syndrome (INS). IgA nephropathy (present in 52%) and other mesangial lesions were found in the majority of the 56 patients with GH. Many of these patients had complex urological procedures prior to consideration of a nephrological problem. This often led to significant delays in making the appropriate diagnosis. Pathological lesions in the 65 patients with INS included minimal change NS (MCNS) in 31%, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS) in 18.5% each, and membranoproliferative GN (MPGN) in 12%. In 47 of the patients with INS, in whom no specific treatment had been given prior to renal biopsy, MCNS and MGN were observed with a similar frequency (26% and 23%, respectively), with FSGS and MPGN being found in 21% and 11%. These results indicate that the pathological lesions in adolescents with INS who undergo a renal biopsy more closely resemble those in adults, and are usually more severe than those in young children. However, it should be noted that our study was retrospective. Hence, there were probably some adolescents with INS who had a successful response to therapy and therefore did not have a renal biopsy performed. Southwest Pediatric Nephrology Study Group (Central Office, Baylor University Medical Center at Dallas, Tex., USA). Director, Ronald J. Hogg; Associate Directors, Fred G. Silva and F. Bruder Stapleton; Statistician, Joan S. Reisch; Administrative Assistant, Kaye Green. Participating Centers—Baylor College of Medicine, Houston, Tex.: Phillip L. Berry, L. Leighton Hill, Sami A, Sanjad, Edith Hawkins; Baylor University Medical Center, Dallas, Tex.: Ronald J. Hogg, Kaye Green; Tulane University Medical Center, New Orleans, La.: Frank Boineau, John E. Lewy, Radhakrishna Baliga, Patrick Walker; University of Arkansas, Little Rock, Ark.: Watson Arnold, Eileen Ellis, Edward Uthman; University of Colorado Health Science Center, Denver, Colo.: Gary M. Lum, Wiliam Hammond; University of Oklahoma Medical Center, Oklahoma City, Okla.: James Wenzl, James Matson, Geoffrey Altshuler, Sarah Johnson; University of Tennessee, Memphis, Tenn.: F. Bruder Stapleton, Shane Roy, III, Robert J. Wyatt, Charles McKay, William Murphy; University of Texas Health Science Center at Dallas, Tex.: Billy S. Arant Jr, Michel Baum, Fred G. Silva, Arthur Weinberg, Craig Argyle, Joseph Rutledge, Ed Eigenbrodt; University of Texas Medical School, Houston, Tex.: Susan B. Conley, Jacques Lemine, Ron Portman, Ann Ince, Regina Verani; University of Texas Health Science Center at San Antonio, Tex.: Michael Foulds, Sudesh Makker, Kanwal Kher, Melanie Sweet, Victor Saldivar, Fermin Tio; University of Texas Medical Branch, Galveston, Tex.: Ben H. Brouhard, Alok Kalia, Luther B. Travis, Lisa Hollander, Tito Cavallo, Srinivasan Rajaraman; University of Utah Medical Center, Salt Lake City; Utah: Eileen Brewer, Richard Siegler, Elizabeth Hammond, Theodore Pysher. Note that this list reflects the investigators' addresses and positions during the period of this study and not necessarily their current situations.     

Microalbuminuria in diabetes: relationships between urinary albumin excretion and diabetes-related variables

A single observer reviewed 842 of the 917 known diabetic patients registered with 40 GPs in the Poole area. Fifty-nine per cent (493) of those reviewed submitted a timed overnight urine collection to measure albumin excretion rate (AER) and overnight albumin/creatinine ratio (ON-Alb/Creat); 43 samples were excluded because of urinary tract infection and/or proteinuria. A random urine sample was obtained in 607 diabetic patients to measure the random albumin/creatinine ratio (R-Alb/Creat); 68 specimens were excluded because of infection and/or proteinuria, and in a further 10 samples urinary creatinine was not measured. Stepwise multiple regression analyses found significant associations with the following variables: for AER, blood glucose (p = 0.001), smoking category (p = 0.002), sex (p = 0.034), and systolic blood pressure (p = 0.035); for R-Alb/Creat, blood glucose (p = 0.001), retinopathy (p = 0.004), systolic blood pressure (p = 0.004), diastolic blood pressure (p = 0.015), coronary artery disease (p = 0.02), sex (p = 0.034), and vibration sense (p = 0.038). Interestingly, glycosylated haemoglobin was not a significant determinant of albuminuria in either analysis.     

Multiple Cerebral Haematomata and Peripheral Nerve Palsies Associated with a Case of Juvenile Diabetic Ketoacidosis

A 15-year-old girl presented de novo in diabetic ketoacidosis having been comatose for 24 h (day 1). A CT scan and lumbar puncture performed on admission were normal and her conscious level slowly improved over several days. On day 7 she had central neurological signs of bilateral knee clonus and an extensor plantar response. In addition, she had developed lower motor neurological signs of an ulnar nerve palsy of the left forearm, and ulnar, median, and radial nerve palsies of the right forearm. Magnetic resonance imaging (MRI), performed on day 12, showed multiple small cerebral haematomata with appearances at least several days of age. The scattered lesions were localized particularly to the parieto-occipital region, with sparing of the basal ganglia and without cerebral oedema, a novel feature not previously described in juvenile ketoacidosis. Four months later there was minimal residual disability of her right arm. The clinical findings together with the MRI images suggested that the peripheral nerve and central lesions were temporally related, suggesting a common aetiology. However, it is likely that MRI showed cerebral lesions which may have been missed by the conventional CT scanning performed initially.