重组人表皮生长因子在瓦斯爆炸Ⅱ°烧伤创面修复中的应用

目的观察重组人表皮生长因子（rhEGF）治疗瓦斯爆炸烧伤创面的疗效和安全性。方法采用开放性临床观察，选择同体、同深度、相近或对称部位烧伤创面，在正规治疗的基础上，局部喷rhEGF或安慰剂（对照组），以创面愈合为指标，判断创面愈合时间，并观察创面动态愈合率及不良反应。结果重组人表皮生长因子治疗浅Ⅱ°创面、深Ⅱ°创面，治疗组较对照组创面愈合时间分别提前3．21和4．36d，组间比较，差异有统计学意义（P〈0．01），未见不良反应。结论rhEGF能够有效地促进深、浅Ⅱ°创面的愈合，未发现药物不良反应。     

碘伏在创面中应用价值的探讨

目的 探讨碘伏在各种创面中的应用价值。方法 对400例各种伤口进行分组,分别用碘伏(为A 组)及普通换药法(为B组)治疗,并观察及比较创面愈合情况。结果 A组愈合时间明显短于B组,感染率明显低于 B组(P值均<0.01)。结论 碘伏用于各种创面,可有效控制伤口感染,促进伤口愈合。在创面中的应用效果理想。     

三氧治疗仪治疗体表损伤性创面的疗效观察

目的:观察三氧治疗仪治疗体表损伤性创面的临床疗效。方法:将120例体表损伤性创面患者随机分为三氧治疗组60例,常规治疗对照组60例,进行对照观察。结果:治疗组与对照组比较,治疗组可以缩短创面愈合时间,提高创面愈合率(P<0.01)。结论:三氧治疗仪治疗体表损伤性创面具有明显抗感染、提高创面愈合率,缩短创面愈合时间的作用。     

湿润烧伤膏治疗褥疮疗效观察

目的为提高褥疮护理质量达到减轻病人痛苦.方法通过对84例共102处褥疮随机分为实验组及对照组即美宝湿润烧伤膏治疗组与传统治疗组.两组患者在性别、年龄、病程和褥疮分期.褥疮面积、营养状况等基本近似情况下观察其两组创面平均愈合天数.结果经整理资料,应用计量资料统计分析有差别显著(P＜0.01).以实验组应用美宝湿润烧伤膏治疗组平均愈合天数少于对照组.结论美宝湿润烧伤膏对褥疮创面有促进愈合作用.     

甲壳胺敷料促进创面愈合的临床观察

目的观察甲壳胺敷料对烧伤患者供皮区创面的愈合影响。方法设立同体对照,将56例取皮创面分成治疗组和对照组,治疗组创面用甲壳素敷料覆盖,对照组创面用凡士林油纱覆盖,两组均定期换药至创面愈合,观察治疗期间两组创面局部变化、细菌计数及愈合时间。结果 56例供皮区创面,平均愈合时间治疗组(9.5±1.6)d,对照组(12.4±2.6)d,两组比较,差异有统计学意义(P<0.05);创面细菌检测率治疗组3.1%,对照组6.5%,差异无统计学意义。结论甲壳胺敷料不加重供皮区创面的感染,有显著的加速创面愈合的作用。     

重组人酸性成纤维细胞生长因子临床应用观察

目的观察重组要酸性成纤维细胞生长因子对创面修复的影响和可能发生的毒副作用。方法将48例深Ⅱ°烧伤患者随机分为两组,治疗组外用aFGF,对照组外用bFGF,比较愈合时间及动态愈合率。观察治疗组用药过程中的不良反应。结果治疗组创面愈合时间为(16．36±3．56)天,对照组为(16．42± 4．33)天,两者愈合时间、愈合百分率比较无统计学差异。治疗组治疗前后未发现明确的毒副作用。结论 aFGF为临床促进创面愈合的又一良好选择。     

早期干预对缺氧缺血性脑病患儿智能发育的影响

目的探讨剖宫产术后切口愈合不良二期缝合方法及临床意义。方法将86例刮宫产术后切口愈合不良分为两组：二期缝合组及单纯换药组，比较两组愈合时间及愈合效果。结果对两组患者愈合时间进行比较，二期缝合切口愈合时间明显缩短，且创面平整，可达到一期愈合效果，无瘢痕挛缩，在美观上明显优于单纯换药组。结论对剖宫产术后切口愈合不良的患者进行二期缝合，既可缩短愈合时间，又减轻产妇痛苦，是一种较好的临床治疗方法，值得推广。     

骨科创伤及感染创面应用VSD治疗的临床疗效分析

目的 探讨封闭负压引流技术（VSD）在骨科创伤及感染创面治疗中的临床疗效与常规引流技术的疗效差异.方法 选择我院于2012年5月-2013年3月接收的70例骨科创伤感染患者,所有患者随机分为观察组和对照组两组,每组均为35例.所有患者在入院后均接受常规彻底清创术,根据对照组患者创面实际情况,每隔1～2 d更换敷料,创面较大的患者需要放置引流条,每隔5～6 d进行一次病原学检查,且使用敏感抗生素进行抗感染治疗;实验组则采用VSD敷料来覆盖创面,每次覆盖的时间是5～7 d,封闭负压吸引直到创面的肉芽丰满后进行创面植皮术,并根据病原学检查结果继续进行抗炎治疗.统计分析实验组和对照组的愈合时间及其总疗效.结果 对照组29例（83％）伤口愈合良好且无渗液,6例患者的治愈效果较差,创面修复时间是7～13 d,平均愈合时间是10.2 d;实验组,33例（94％）患者伤口愈合良好且无渗液,愈合效果较差者2例,创面修复时间是5～9d,平均愈合时间是6.7 d.与对照组相比,实验组患者的伤口愈合率明显升高,伤口平均愈合时间明显缩短,两组之间的差异具有统计学意义（P＜0.05）.结论 VSD技术应用于骨科创伤及感染创面治疗时,能很好的修复创伤面,提高治愈率,其临床治疗效果明显优于传统的引流技术,值得在临床治疗中推广使用.     

美宝（MEBO）联合碱性成纤维细胞生长因子（bFGF）在小儿深Ⅱ°烧伤创面的应用

目的探讨美宝联合碱性成纤维细胞生长因子治疗小儿深Ⅱ°烧伤创面的临床疗效。方法选择我科2008年9月至2011年4月135例因热开水烫伤四肢皮肤致深Ⅱ°烧伤的小儿患者,按创面处理方法分为A组和B组。A组（66例）采用美宝联合碱性成纤维细胞生长因子治疗,B组（69例）单独采用美宝进行治疗。对两组创面的愈合时间及愈合后瘢痕形成等情况进行比较。结果 A组平均愈合时间（14.8±2.7）天,愈后瘢痕少;B组平均愈合时间（16.2±2.7）天,愈后瘢痕少。两组愈合时间有显著性差异（P〈0.01）。结论联合应用美宝和碱性成纤维细胞生长因子治疗小儿深Ⅱ°烧伤创面,可加速创面愈合,愈后瘢痕形成无明显差异。     

龙血竭在项背痈治疗中的应用

目的探讨龙血竭在项背痈治疗中的临床疗效。方法将2008年2月～2013年2月间我科64例项背痈患者按入院顺序随机分为治疗组和对照组,行单盲前瞻性随机对照临床研究。两组患者均于入院后急诊行“＋”字切开引流,治疗组用龙血竭片研磨而成的粉沫均匀撒于创面,然后用优锁儿湿纱条填塞包扎。对照组单纯用优锁儿湿纱条填塞包扎。对两组患者术后渗血量、术后疼痛、平均愈合时间、瘢痕大小进行观察并统计分析。结果治疗组在创面切开后渗血量、术后疼痛、平均愈合时间、瘢痕大小方面情况均优于对照组（p〈0．05）。结论在项背痈切开术后的换药治疗中加入龙血竭粉可以减少术后渗血及疼痛,促进创面愈合,缩短临床愈合时间,减轻患者负担,减少瘢痕形成,是项背痈治疗的一种较好的换药方法。     

Methods for assessing difference between groups in change when initial measurement is subject to intra-individual variation

Statistical analysis of difference between groups in change for some variable, adjusting for initial value, is complicated by the presence of intra-individual variation in that variable. We estimate here the asymptotic bais that results from calculating the adjusted between-group difference by ordinary least squares (OLS) from observed data. We also present explicit formulae that use the OLS estimates, the difference between treatment groups in mean initial values, and a measure of the intra-individual variation to compute a corrected estimator and its variance. Alternatively, we can use OLS on transformed data to obtain unbiased estimates, in which we replace initial observed values by conditional Stein estimates of true values. We illustrate the results with data from an observational study and a clinical trial.     

Study duration for group sequential clinical trials with censored survival data adjusting for stratification.

The study duration in a clinical trial with censored survival data is the sum of the accrual duration, which determines the sample size in a traditional sense, and the follow-up duration, which more or less controls the number of events to be observed. We propose a design procedure for determining the study duration or for calculating the power in a group sequential clinical trial with censored survival data and possibly unequal patient allocation between treatments, adjusting for stratified randomization. The group sequential method is based on the use function approach. We describe a clinical trial recently activated by the Eastern Cooperative Oncology Group for an illustration of the proposed procedure.     

临床意义与统计学意义结合的临床试验结果分类方法及评价研究

目的 统计学意义在临床试验结果解读中发挥重要作用，但在获得有统计学意义结果时，临床意义的评估常被忽略，本研究尝试提出一种简单且明确的试验结果新分类方法，重点针对已获得统计学阳性的试验，评估其结果是否具有临床意义。方法 以2019年美国心脏病学会（ACC）和欧洲心脏病学会（ESC）大会公布结果的临床试验为研究对象，通过荟萃流行病学方法，提取研究水平的特征变量。主要评价指标包括试验设计阶段假设的目标效应值及试验结果所得的观察效应值，基于两者间的差异，对已获得统计学阳性的试验进行细分，识别出临床意义可能不充分的研究；并基于检验把握度的理论提出阈值，作为对该类问题进行识别的基础。结果 最终纳入分析的12项临床试验多发表于顶尖专业期刊、具有较高的研究设计与报告质量；观察效应值与目标效应值间有一定相关性（r=0.892），但基于两者间的差异，并聚焦获得了有统计学意义结果的7项试验，其中被分类为临床意义不充分的共2项，按ACC和ESC公布的试验进行划分，有统计学意义却可能无临床意义的研究各1项（1/3和1/4）。结论 已获得统计学阳性结果的试验，仍有必要对其临床意义的充分性进行评估，本研究提出一种新的将临床意义与统计学意义结合的分类标准及在其基础上对临床试验结果可靠性进行评估的方法，辅助研究者识别因临床意义不充分导致的潜在风险，为临床研究结果的合理解读提供一定的参考和帮助。     

Exploring the benefits of adaptive sequential designs in time-to-event endpoint settings

Sequential analysis is frequently employed to address ethical and financial issues in clinical trials. Sequential analysis may be performed using standard group sequential designs, or, more recently, with adaptive designs that use estimates of treatment effect to modify the maximal statistical information to be collected. In the general setting in which statistical information and clinical trial costs are functions of the number of subjects used, it has yet to be established whether there is any major efficiency advantage to adaptive designs over traditional group sequential designs. In survival analysis, however, statistical information (and hence efficiency) is most closely related to the observed number of events, while trial costs still depend on the number of patients accrued. As the number of subjects may dominate the cost of a trial, an adaptive design that specifies a reduced maximal possible sample size when an extreme treatment effect has been observed may allow early termination of accrual and therefore a more cost-efficient trial. We investigate and compare the tradeoffs between efficiency (as measured by average number of observed events required), power, and cost (a function of the number of subjects accrued and length of observation) for standard group sequential methods and an adaptive design that allows for early termination of accrual. We find that when certain trial design parameters are constrained, an adaptive approach to terminating subject accrual may improve upon the cost efficiency of a group sequential clinical trial investigating time-to-event endpoints. However, when the spectrum of group sequential designs considered is broadened, the advantage of the adaptive designs is less clear.     

An exploratory instrumental variable analysis of the outcomes of localized breast cancer treatments in a medicare population

This study is motivated by the potential problem of using observational data to draw inferences about treatment outcomes when experimental data are not available. We compare two statistical approaches, ordinary least-squares (OLS) and instrumental variables (IV) regression analysis, to estimate the outcomes (three-year post-treatment survival) of three treatments for early stage breast cancer in elderly women: mastectomy (MST), breast conserving surgery with radiation therapy (BCSRT), and breast conserving surgery only (BCSO). The primary data source was Medicare claims for a national random sample of 2907 women (age 67 or older) with localized breast cancer who were treated between 1992 and 1994.Contrary to randomized clinical trial (RCT) results, analysis with the observational data found highly significant differences in survival among the three treatment alternatives: 79.2% survival for BCSO, 85.3% for MST, and 93.0% for BCSRT. Using OLS to control for the effects of observable characteristics narrowed the estimated survival rate differences, which remained statistically significant. In contrast, the IV analysis estimated survival rate differences that were not significantly different from 0. However, the IV-point estimates of the treatment effects were quantitatively larger than the OLS estimates, unstable, and not significantly different from the OLS results. In addition, both sets of estimates were in the same quantitative range as the RCT results.We conclude that unadjusted observational data on health outcomes of alternative treatments for localized breast cancer should not be used for cost-effectiveness studies. Our comparisons suggest that whether one places greater confidence in the OLS or the IV results depends on at least three factors: (1) the extent of observable health information that can be used as controls in OLS estimation, (2) the outcomes of statistical tests of the validity of the instrumental variable method, and (3) the similarity of the OLS and IV estimates. In this particular analysis, the OLS estimates appear to be preferable because of the instability of the IV estimates.     

The Quality of Life of Parents of Children with Atopic Dermatitis: Interpretation of PIQoL-AD Scores

The PIQoL-AD has been used in several trials assessing quality of life (QoL) in parents of children with atopic dermatitis (AD), treated with pimecrolimus cream 1%. Secondary analysis of data from four trials (n = 621) was undertaken to help interpret the meaningfulness (significance) of the QoL results. A combination of anchor-based and distribution-based methods of interpreting instrument scores were employed. For each level on four AD severity indicators, mean PIQoL-AD scores and 95% confidence intervals were calculated. Low levels of association (r_s range = 0.12–0.45) were observed between QoL and clinical indicators; confirming previous findings. When data from the different trials and time-points were combined clear patterns emerged indicating the clinical meaning of PIQoL-AD scores. Distribution-based statistics such as effect sizes, the standard error of measurement (SEM) and the standard error of difference (S_diff) were also calculated. Despite a lack of consensus on how best to determine the meaningfulness of QoL scores, a large database of trial data was successfully used to link QoL scores to disease severity, aiding clinical interpretation of the former. Effect size, SEM and S_diff values were consistent across the trials indicating that a change of 2 to 3 PIQoL-AD points over time could be considered meaningful. It is argued that it would be useful for clinicians to gain an understanding of the meaning of QoL scores through routine use of such measures in clinical practice.     

A new graphic for quality adjusted life years (Q-TWiST) survival analysis: The Q-TWiST plot

One of the challenges of interpreting a Quality-adjusted time without symptoms of disease and toxicity (Q-TWiST) analysis is examining the sensitivity of conclusions that may be drawn to varying values of the utility coefficients for days with toxicity and days after disease progression. We present a graphic that parsimoniously displays the impact on median Q-TWiST survival across treatment groups of varying values of the utility coefficients. The goal of the graphic is to present a concise Q-TWiST analysis. We use Zhao and Tsiatis (Biometrika 1997; 84(2): 339–348) to adjust for the bias in Kaplan-Meier (K-M) estimates. The graphic contains bounds that approximate points for which statistical significance would be achieved by comparing the median Q-TWiST survival between treatment alternatives for each value of the utility coefficients. The plot may be generalized to compare Q-TWiST means, medians or percentiles across treatment groups. We demonstrate the application of the Q-TWiST plot through a re-analysis of a randomized phase III North Central Cancer Treatment Group (NCCTG) clinical trial of recombinant Interferon-2 in patients with malignant melanoma. We explore alternative options to customize the graphic representation for other data sets drawn from several NCCTG clinical trials.     

Repeated significance tests on accumulating survival data.

The aim of the study was to compare the properties of two well-known group sequential methods and to demonstrate the effect of performing interim analyses on accumulating survival data without making appropriate adjustments of the nominal significance level. The properties of a group sequential method with fixed nominal significance level (Pocock stopping boundaries) and a method with increasing nominal level with each interim analysis (O'Brien-Fleming boundaries) were compared by stochastic simulation. Simulation experiments with survival times sampled from a breast cancer trial and from exponential distributions were performed. The true overall significance level with unplanned interim analyses increased from 5% to 14% when a maximum of five tests were performed. Both group sequential methods maintained the desired overall significance level. The O'Brien-Fleming method had higher power than Pocock's method. It also reduced the risk of early stopping based on immature data and should usually be preferred.     

Treatment with fluorated quinolones of febrile neutropenia in patients with hematologic malignancies

The use of fluoroquinolones in the treatment of cytotoxic therapy-induced febrile neutropenia is controversial. AIM: The aim of the study was to compare the therapeutic effect of fluoroquinolones with that of standard antibiotic regimens in patients with hematologic malignacies and febrile neutropenia following antineoplastic chemotherapy. PATIENTS AND METHODS: This is a prospective randomized study including 129 patients with 141 neutropenic episodes divided into two groups. Fluoroquinolones are used in the trial group and broad-spectrum beta-lactam antibiotics in the control group. The data are analyzed using alternative analysis, non-parametrical chi-square test and Student-Fisher t-test. RESULTS: The febrile neutropenic episodes were classified as fever of unknown origin (50.4%) and documented infection (49.6%). In the category "fever of unknown origin" no statistically significant difference was found in the clinical effect, patient survival, general and infectious lethality between the trial and control group. In the category "documented infection" the trial group showed significantly lower therapeutic effect and lower infection-free survival of the patients. The clinical effect and infection-free survival after treatment with fluoroquinolones were significantly lower in the category "documented infection" than in the category "fever of unknown origin". CONCLUSION: Fluoroquinolones can be alternative drugs to the standard antibiotic regimens in the treatment of febrile neutropenia in cases of fever of unknown origin. Fluoroquinolone monotherapy is not recommended in cases of febrile neutropenia with documented infection.