Conditional estimation of sensitivity and specificity from a phase 2 biomarker study allowing early termination for futility

Development of a disease screening biomarker involves several phases. In phase 2 its sensitivity and specificity is compared with established thresholds for minimally acceptable performance. Since we anticipate that most candidate markers will not prove to be useful and availability of specimens and funding is limited, early termination of a study is appropriate, if accumulating data indicate that the marker is inadequate. Yet, for markers that complete phase 2, we seek estimates of sensitivity and specificity to proceed with the design of subsequent phase 3 studies. We suggest early stopping criteria and estimation procedures that adjust for bias caused by the early termination option. An important aspect of our approach is to focus on properties of estimates conditional on reaching full study enrollment. We propose the conditional‐UMVUE and contrast it with other estimates, including naïve estimators, the well‐studied unconditional‐UMVUE and the mean and median Whitehead‐adjusted estimators. The conditional‐UMVUE appears to be a very good choice. Copyright © 2008 John Wiley & Sons, Ltd.     

高浓度瘦素自分泌诱导脂肪细胞瘦素抵抗的研究

目的:观察高浓度瘦素对人脂肪细胞分解代谢及脂肪蓄积的直接影响,探讨瘦素自分泌调节在肥胖发生中的作用。方法:取正常成人皮下脂肪组织,常规提取和培养前脂肪细胞,待细胞融合后诱导分化为脂肪细胞后分为二组:低浓度组、高浓度组;分别培养于瘦素终浓度为100ng/ml、1000ng/ml的培养液a中。于培养48h、72h收集培养液检测游离脂肪酸和甘油的浓度,取脂肪细胞行油红O染色并图像分析计算脂肪细胞中脂肪颗粒的积分光密度。结果:与低浓度组相比,瘦素作用48h、72h后,高浓度组培养液中游离脂肪酸浓度均下降[(0.16711±0.011900)mmol/L VS(0.20589±0.008738)mmol/L,(0.17544±0.013920)mmol/L VS(0.23567±0.026220)mmol/L,甘油含量均减少(28.1733±0.91377)μmol/L VS(30.2456±0.30084)μmol/L,(28.9367±0.79530)μmol/L VS(31.8567±0.79024)μmol/L],而脂肪颗粒积分光密度则升高(461136.89±12049.947 VS418570.33±5668.129,441566.56±5921.602 VS 390133.67±7001.304)。结论:高浓度瘦素长时程作用脂肪细胞,可延缓脂肪分解代谢,增加脂肪蓄积。高浓度瘦素经自分泌诱导脂肪细胞产生瘦素抵抗,可能对肥胖发生有重要影响。     

后路减压植骨融合3D脊柱内固定系统治疗腰椎滑脱症

[目的]观察3D脊柱内固定系统对腰椎滑脱症的固定及治疗效果。[方法]2004年1月～2005年7月,对42例腰椎滑脱症患者(其中,男28例,女14例)运用椎板减压、椎管后外侧植骨融合、3D椎弓根螺钉内固定系统治疗,随访13～32个月(平均25.3个月)。[结果]术前JOA评分平均4.48分的42例患者,随访时14.5分(P<0.01),术后15个月内动态X线检查显示3D椎弓根螺钉固定患者植骨融合率100%,融合节段稳定,临床症状改善优良率92.8%。[结论]后路运用3D内固定系统行椎管后外侧植骨融合内固定对腰椎滑脱症患者是一种安全、有效的术式,近期疗效满意。     

BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

肱骨髁间骨折的手术治疗及疗效评价

目的 探讨肱骨髁间骨折的手术方式并评价疗效。方法 1998年1月～2004年12月共手术治疗肱骨髁间骨折28例，进行随访分析。结果 28例中26例获随访，时间6个月～4年7个月，其中22例获2年以上随访。疗效评价参照casse‰。评分系统，优良率为65％。结论 骨折类型及手术方式直接影响预后。关节良好的复位和牢固的固定，以及术后早期积极的功能锻炼是得到良好疗效的保证。     

过敏性疾病63例生物共振脱敏效果观察

目的观察生物共振治疗系统对过敏性疾病进行脱敏治疗的效果。方法应用生物共振治疗仪对135例过敏性疾病患者进行过敏原测定,并对其中63例进行系统的脱敏治疗。结果63例患者脱敏治疗的总优良率为82.5%。变应性皮炎、过敏性鼻炎、过敏性哮喘三组比较差异无统计学意义(P>0.05)。单纯变应性皮炎较单纯变应性皮炎合并其他过敏症患者的疗效显著(P<0.01)。结论生物共振脱敏治疗无任何不良反应,是一种比较理想的过敏性疾病的治疗方法。     

含丙醇基质护手霜中的润肤剂能显著减轻刺激性接触性皮炎

本研究旨在确定含丙醇护手霜的润肤剂对皮肤干燥和红斑的作用。35例受试者参与该前瞻性、随机、对照、双盲试验，其中约半数具有遗传过敏体质（改进的Erlanger遗传过敏体质评分≥8）。应用两种含丙醇基质的制剂进行反复开放敷贴试验，其中一种含混和润肤剂（0．81％，w／w）。每一制剂两等分各为0．7ml，随机分配给所有受试者后涂至肘窝皮肤，2次／d，持续两周以上。在每次用药前和最后一次用药3d后，根据标准评分，通过视觉检测评估治疗部位的红斑和干燥情况。所有评价时点的总分作为原始参数。     

颈椎后路螺钉-钛棒(板)内固定技术:初步临床报告

目的 报告利用螺钉-钛棒（板）固定技术治疗各种原因引起的颈椎不稳的初步临床结果。方法 作者1年来行颈椎后路螺钉-钛棒（板）技术内固定9例，其中齿突样骨引起的C1～C2不稳2例，手术后进行性颈椎后凸2例，颈椎管狭窄2例，C3-C4滑脱1例，C6～C7外伤滑脱2例。分别采用C1侧块、C2椎弓根螺钉、C3～C5侧块螺钉、C2-T2椎弓根螺钉植入技术，然后连接钛棒或钛板完成固定。9例病人共植入螺钉59枚。结果 所有病人在1周内带外支架进行活动，除1例因拒绝治疗死亡外，其余病人在1个月及1年后复查均未见内固定物移位。结论 颈椎后路螺钉-钛棒（板）固定为安全可靠的技术，可以术后即刻获得牢固内固定，为下一步治疗创造有利条件。