Multiplicity Adjustment for Clinical Trials With Two Doses of an Active Treatment and Multiple Primary and Secondary Endpoints

Frequently, two doses of an active treatment, multiple primary and secondary endpoints are simultaneously considered in Phase III confirmatory clinical trials. For these trials, many traditional multiplicity adjustment procedures do not take into account the possible dose effect on each endpoint and the priority order of the primary and secondary endpoints, and therefore may have lower power. To gain power, we consider the problem as a three-dimensional multiplicity problem: one dimension concerns the multiple doses, one dimension concerns the priority order of the primary and secondary endpoints, and another dimension concerns the multiple endpoints in each priority category. We propose procedures that consider the dose order and the priorities of the endpoints to form closed procedures and therefore control the family-wise error rate. Furthermore, we consider procedures that provide control of type I error rates in clinically relevant subfamilies of comparisons, providing a pragmatic approach to maintain study power as compared to the traditional approaches for the ultimate overall strong control. Simulation results and a real data example show that the procedures proposed in this article in general are easy to use and have improved power.     

关节镜下微创治疗与切开复位内固定治疗胫骨平台骨折疗效的Meta分析

目的：采用Meta法分析比较关节镜下微创治疗与切开复位内固定治疗SchatzkerⅠ～Ⅳ型胫骨平台骨折的疗效。方法全面检索国内外关于关节镜下微创与传统切开复位内固定治疗胫骨平台骨折疗效的随机对照研究,经过特定的纳入、排除标准筛选文献,临床评价指标包括术后Sanders膝关节功能评分优良率、切口长度、手术时间、术中出血量、解剖复位率。采用RevMan5.0软件对纳入试验数据进行Meta分析。结果共纳入随机对照研究文献4篇,共计419例胫骨平台骨折患者,其中关节镜下经皮切开复位内固定组（arthroscopicreductionandinternalfixation,ARIF组）205例,传统切开复位内固定组（openreductionandinternalfixation,ORIF组）214例。Meta分析结果显示,与ORIF组相比,ARIF组Sanders膝关节功能优良率明显增加[OR＝1.78,95%CI（1.07,2.97）,P＜0.05],差异有统计学意义;同时切口长度减小[WMD＝-12.12,95%CI（-12.69,-11.54）,P＜0.05]、术中出血量减少[WMD＝-61.99,95%CI （-64.21,-59.78）,P＜0.05]及解剖复位率增高[OR＝3.00,95%CI（1.16,7.75）,P＜0.05],差异均有统计学意义;两组在手术时间上差异无统计学意义[WMD＝0.80,95%CI（-0.64,2.24）,P＞0.05]。结论与ORIF治疗胫骨平台骨折相比较, ARIF治疗SchatzkerⅠ～Ⅳ型胫骨平台骨折有创伤小、术中出血量少、解剖复位率高及术后膝关节功能优良率高等优点;但与ORIF组手术时间相比,ARIF组未见明显优势。     

Clinical effectiveness of antibiotic-impregnated cement spacers for the treatment of infected implants of the hip joint

It is difficult to treat an infected implant of the hip joints, as it requires long-term treatment and eventually may lead to amputation or arthrodesis, involving immeasurable physical and psychological suffering for the patient. We utilized antibiotic-impregnated cement spacers for 17 infections after total hip arthroplasty and bipolar arthroplasty with good clinical results. We thoroughly removed any foreign material and formed an antibiotic-impregnated cement spacer into a shape similar to that of the implants. This enabled high-concentration antibiotics to act on the infected sites. It also can prevent leg-length discrepancy and atrophy of bones or muscles. Although cement spacers have been reported to have problems regarding shape and strength, we achieved good results with cement spacer molds in the present study. All revision surgeries were performed using a two-stage procedure. No infection has recurred at a mean follow-up of 3 years 2 months.     

PELD及 MED治疗腰椎间盘突出症的临床比较研究

目的：比较经皮内窥镜下腰椎间盘切除术（PELD）与后路显微内窥镜下腰椎间盘切除术（MED）治疗腰椎间盘突出症（LDH）的临床疗效。方法：采用前瞻性随机对照研究的方法,选取2012年2月－2013年6月90例术前确诊为单节段腰椎间盘突出症的患者,随机分为PELD组和MED组各45例,采用视觉模拟量表（VAS）评分和Oswestry功能障碍指数（ODI）评估疗效。结果：所有患者均顺利完成手术。PELD组平均术中透视次数16．4次,切口长度8．5mm,手术时间88．3min,手术失血10．8mL,术后卧床5．9h,住院3．6d;MED组平均术中透视次数2．5次,切口长度16．4mm,手术时间51.4min,手术失血32．8mL,术后卧床73．1h,住院6．5d。PELD组较MED组术中透视次数更多、手术时间更长,差异具有统计学意义（P〈0．05）;但在手术切口长度、手术出血量、术后卧床时间和住院时间的比较上,PELD组优于MED组,差异具有统计学意义（P〈0．05）。两组术后VAS、ODI评分与术前比较,均明显改善（P〈0．05）,两组之间VAS评分、0DI评分术后改善率比较差异无统计学意义（P〉0．05）。结论：在严格选择手术适应证的情况下,PELD和MED均具有安全有效、手术创伤小、出血量少、并发症发生率低、术后恢复快等优点,但是PELD是一种更加理想的微创手术。     

小切口非超声乳化白内障摘出人工晶状体植入联合小梁切除术治疗青光眼合并白内障

目的 报告小切口非超声乳化白内障摘除人工晶状体植入联合小梁切除术治疗青光眼合并白内障的患眼术后效果.方法 收集青光眼合并白内障19例,行小切口非超声乳化白内障摘出人工晶状体植入联合小梁切除术,观察术后眼压、视力、滤过泡和并发症.结果 术后眼压在14～18mmHg之间,平均为（15.26±1.20）mmHg,与术前眼压有显著性差异（P＜0.05）;术后视力较术前均有不同程度提高,术后视力＜0.05者6眼,0.05～0.3者8眼,＞0.3者5眼;术后滤过泡Ⅰ型、Ⅱ型17眼（89.47％）,为功能型滤过泡,2眼（10.53％）滤过泡不明显;未见严重并发症.结论 小切口非超声乳化白内障摘除人工晶状体植入联合小梁切除术治疗青光眼合并白内障是一种安全有效的方法.     

Peribulbar anesthesia in 750 patients treated with oral anticoagulants

AIM: To check the safety of continuation of oral anticoagulants in ophthalmic procedures requiring a peribulbar anesthesia. METHOD:A prospective case control study included 750 patients with oral anticoagulants in group A and 750 patients who had never been treated with oral anticoagulant in group B. Hemorrhages were graded as follows:1) spot ecchymosis of eyelid and or subconjunctival hemorrhage; 2) eyelid ecchymosis involving half of the lid surface area; 3) eyelid ecchymosis all around the eye, no increase in intraocular pressure; 4) retrobulbar hemorrhage with increased intraocular pressure.RESULTS: In group A, grade 1 was observed in 13 patients (1.74%) and grade 2 in 2 patients (0.26%). In group B, grade 1 was observed in 12 patients (1.6%) and grade 2 was absent. No 3 or 4 hemorrhage grade was encountered in both groups. There was not significant difference in grade 1 hemorrhage between both groups (P=0.21).CONCLUSION:Oral anticoagulants were not associated with a significant increase in potentially sight-threatening local anesthetic complications.     

热毒宁注射液原药材——金银花规范化生产研究

为了保证热毒宁注射液原药材——金银花的真实、安全、有效、质量稳定可控,按照我国中药材生产管理规范(GAP)生产的综合技术要求,对其生产中的产地适宜性、种植、田间管理、病虫害综合防治、采收加工、包装贮藏、运输、质量监测等技术要求进行了生产调查和实验研究,制定出了该标准操作规程,并对规范化种植基地建设过程中的经验和问题进行了分析和展望。     

宫颈电环切除术结合保妇康栓治疗宫颈上皮内瘤变临床观察

目的:观察宫颈电环切除术结合保妇康栓治疗宫颈上皮内瘤变临床疗效。方法:将宫颈上皮内瘤病患者100例,随机分为2组各50例,治疗组采取高频电波刀电环切除术配合药物保妇康栓进行治疗,对照组采取单纯高频电波刀电环切除术进行治疗,观察术后疗效并随访观察患者康复情况。结果:2组术后随访3月,治疗组和对照组在手术期间的手术时间及术中出血量比较,差异均无显著性意义(P0.05);治疗组经术后每晚配合保妇康栓治疗,切口愈合时间短于对照组,2组比较,差异有显著性意义(P0.05)。经治疗,治疗组治愈率为86.0%,优于对照组的44.0%,2组比较,差异有显著性意义(P0.05)。结论:高频电波刀电环切除术配合药物保妇康栓治疗宫颈上皮内瘤变临床疗效显著,具有愈合快、低复发、高治愈的特点,值得推广应用。     

密度梯度离心法分离脐血干细胞：分离介质的筛选

背景：应用脐血分离干细胞的目的是获得以干细胞为主要群体的单个核细胞群,密度梯度离心法是最简单有效的方法之一。密度梯度离心法使用的分离介质以聚蔗糖泛影葡胺最为常用,但哪种浓度获得干细胞最多,目前尚未深入研究。目的：探讨密度梯度离心法分离人脐血干细胞分离介质的最佳浓度,建立临床级干细胞分离应用方案。方法：采用两步法分离脐血流程,先用羟乙基淀粉沉淀脐血红细胞,再使用质量浓度分别为（1．073O±0．0001）,（1．0750±0．0001）,（1．077O±0．0001）g／mL的分离液,分离沉淀脐血红细胞后的上清液,得到单个核细胞,分别计数细胞获得率及细胞存活率。采用流式细胞仪测定单个核细胞表面标志物,将各亚组分绘制成直方图或散点图,分析所得脐血单个核细胞中所含单个核细胞亚组分的比例和绝对数量。结果与结论：应用质量浓度（1．0730＋0．0001）g／mL的分离液可得到最大比例间充质干细胞群,是分离间充质干细胞的最佳质量浓度。使用质量浓度（1．0750±0．0001）g／mL的分离液可得到较高比例的造血干细胞群,是分离造血干细胞的最佳质量浓度。使用质量浓度（1．0770±0．0001）g／mL的分离液得到细胞总数最高,但获得的间充质干细胞、造血干细胞比例最低。采用两步法分离干细胞流程,建立严格的实验室条件和标准,可获得密度梯度离心法分离人脐血干细胞的最佳分离方案。     

六西格玛管理法在日间化疗病房护理管理中的应用

目的探讨六西格玛管理模式对日间化疗病房进行管理的效果。方法组建六西格玛项目管理团队并进行培训,分析影响质量管理的因素,优化住院流程、输液流程,对护理人力资源进行调整,加强输液安全保障措施。结果患者输液等待时间缩短,化疗药物外渗发生率降低,护士工作满意度、患者满意度提高（P〈0．01或P〈0．05）。结论应用六西格玛管理模式能优化输液流程和住院流程,提高患者满意度。