2010至2014年参加卫生部血铅检测室间质评结果回顾分析

目的通过回顾分析2010至2014年参加卫生部临床检验中心血铅检测室间质量评价(EQA)的成绩,探讨稳定和提高血铅检测质量的因素,为实验室全面质量管理的实施提供科学依据。方法采用偏差、能力比对(PT)得分和Z比分数对2010至2014年7个批次35份EQA成绩进行统计分析。结果分析2010~2014年5年内参加卫生部临床检验中心血铅检测EQA的成绩,偏差符合卫生部临床检验中心要求,均属在控范围;能力比对得分均为100%;Z比分数2.0,均为满意。结论本实验室的血铅检测系统完全胜任大批量样本的检测需求。在EQA统计中,Z比分数能更好剔除离群值的影响,更全面客观地反映参评者的检测水平,可作为新的EQA统计方法。     

多种统计学方法对实验室间定量检测结果的比对研究

目的用多种统计学方法评价医疗机构间临床检验结果的可比性。方法以葡萄糖检测为例,选择20家临床实验室,对10份新鲜血浆进行重复检测,分别用传统统计学、稳健统计学、3种医学决定水平下的偏移及稳健Z比分数进行分析。结果稳健变异系数为2.57%～4.51%;小于最佳允许偏移的占28.3%(17/60),小于适当允许偏移的占56.7%(34/60),小于最低允许偏移的占63.3%(38/60);稳健Z比分数>90%介于-2与+2。结论各种统计方法从多个方面全面评价了检验结果间的可比性,适用于医疗机构间临床检验结果互认的研究。     

双水平校准纠正苦味酸法肌酐检测偏移

目的通过临床检验实验室间质量评价(室间质评)分析苦味酸法检测肌酐的偏移及校准对偏移的影响。方法利用重庆市临床检验室间质评数据,开展冰冻混合人源血清(参考方法赋值)调查,分析苦味酸法与酶法肌酐检测结果间的差异及偏移;用双浓度水平冰冻混合人源血清(参考方法赋值)校准常规检测系统后检测室间质控品。结果 2012年至2016年重庆市苦味酸法肌酐检测实验室数下降;苦味酸法实验室稳健均值与酶法存在差异,且差值与肌酐水平有相关性(r=0.774 6);冰冻混合人源血清(参考方法赋值)调查及国家卫计委临床检验中心正确度验证结果均显示,苦味酸法肌酐在低浓度存在正偏移(最大达10.39%和13.31%),且偏移与浓度相关(r=0.988 9),而酶法肌酐的偏移较小(最大达1.04%和1.49%);用冰冻混合人源血清校准常规检测系统后,苦味酸法肌酐检测在低浓度的正偏移被抵消。结论苦味酸法肌酐检测在低值范围存在正偏移,双浓度水平校准可纠正此偏移。     

四分位数稳健统计和迭代稳健统计在室间质量评价结果分析中的比较

摘要：目的：比较四分位数稳健统计和迭代稳健统计在定量检测指标室间质量评价（EQA）数据处理中的应用。 方法：分析2012年参加上海市临床检验中心常规化学第1次EQA酶法检测肌酐的实验室结果,用四分位数稳健统计和迭代稳健统计分别进行统计。 结果：2种方法确立的靶值基本相同,迭代稳健统计的标准差、变异系数较四分位数稳健统计大,稳健Z比分数值偏离0的程度总体上较四分位数法小,不合格实验室数较四分位数稳健统计少。 结论：相对于四分位数稳健统计,迭代稳健统计是一种更宽松可靠的统计方法。     

我国肌酐检测系统性能分析

目的研究我国肌酐检测系统的检测性能。方法通过向全国1 402家实验室发放5个不同浓度批次的质评物,进行肌酐检测的实验室室间调查,同时收集各实验室2011年5月肌酐室内质量控制(IQC)信息,按照2种检测方法(苦味酸法和酶法)和11套检测系统分组分析。计算各检测系统室间质量评价(EQA)结果,剔除离群值后的均值(x珋)、标准差(s)、变异系数(CV)。以1/3允许总误差(TEa)和基于生物学变异的质量规范判断各检测系统的不精密度水平。采用各实验室EQA的平均偏差作为偏倚估计,IQC累积CV作为不精密度估计,计算各实验室的西格玛(σ)水平。结果 EQA结果分析中,苦味酸法组CV范围为1.03%～18.23%,酶法组为1.50%～8.08%。苦味酸法组中Beckman检测系统实验室间的变异情况较其他系统好,Beckman UniCel系列检测系统CV范围为3.13%～4.90%。酶法组中以HITACHI系列(Roche)检测系统的变异情况优于其余各组,CV为1.50%～3.00%。IQC结果分析中,80%以上的实验室通过1/3 TEa的质量规范,70%以上的实验室通过基于生物学变异最低质量规范。σ水平分析中,σ度量值>6的实验室酶法组约43%,苦味酸法组约23%。结论肌酐不同检测系统实验室间变异情况酶法组优于苦味酸法组,多数检测系统的不精密度水平满足生物学变异的最低标准,酶法组的σ水平优于苦味酸法组。我国实验室肌酐的检测性能还有待于进一步提高。     

精液检验室间质量评价统计学方案的比对研究*

摘要:目的通过 比较不同统计学方案对精液检验室间质评结果的影响,选择合适的统计学方案进行推广。方法以精子浓度为例,选择2022年湖南省20家实验室精液室间质评数据,分别用传统统计方案、稳健统计方案以及结合稳健统计技术剔除 “离群值”后的传统统计进行分析比对,比较其优劣。结果4组精子浓度数据经传统统计无法剔除“离群值”,与Robust稳健统计方法或结合稳健统计技术剔除“离群值”后的传统统计室间质评结果有差异,传统统计与稳健统计合格实验室数分别为: 19us 16、19us 16、19us 19、19vs 19。结论传统统计方法不适用 于不符合正态分布、数据量较小、可能存在较多“离群值”的精液检验室间质评统计,推荐使用Robust 稳健统计方法;或结合稳健统计技术剔除“离群值”后,可得到与稳健统计方案相似的结果。     

临床检验室间质量评价数据中离群值的研究

室间质量评价是质量控制的重要手段之一，是以靶值作为评价的标准。因此，正确地设定靶值至关重要。大多数定量测量项目的室间质量评价是以所有参加实验室的原始数据或分组后的原始数据的算数平均值加／减k倍（k=2、2．5或3）标准差范围外的数据作为离群值。剔除离群值后以剩余数据的算数平均值作为靶值，这种剔除离群值的方法是假设原始数据是正态分布，实际上原始数据经常不是正态分布，若有一个非常极端的离群值，必定导致靶值的偏移，影响室间质量评价结果的可靠性。因此，离群值必需从原始数据中剔除。如何剔除离群值依据原始数据的分布特性，本研究将探讨利用传统统计法和稳健统计技术剔除离群值。     

苦味酸法和酶法检测肌酐对肾小球滤过率预测公式效能的影响

目的 探讨应用苦味酸法和酶法检测肌酐对GFR评估方程适用性的影响.方法 选取2007-2009年华北(北京)、东北(大连)、华东(上海)、华中(长沙)4个区域三级甲等综合医院CKD患者176例.以双血浆法99m Tc-二乙三胺五乙酸(99mTc-DTPA)血浆清除率作为176例CKD患者的rGFR.使用4个不同厂家的酶法或苦味酸法肌酐试剂配套不同厂家自动生化分析仪分别测定患者血肌酐,同时应用体表面积( BSA)标化的Cockcroft-Gault方程(CG/BSA方程)、简化MDRD方程、校正至同位素稀释质谱法的简化MDRD方程(MDRD-IDMS方程)、CKD流行病学合作研究方程(CKD-EPI方程)及2个国内简化MDRD改良方程(课题组方程1、2)分别计算eGFR,比较不同估算结果与rGFR的相关性、偏差、精密度以及30％准确性.结果 176例CKD患者的rGFR为[40.70(19.41～84.35)] ml·min-1·(1.73 m2)-1.应用苦味酸法测定肌酐时,各方程评估的eGFR与rGFR的ICC在0.879～0.923之间;应用酶法测定肌酐时,各方程评估的eGFR与rGFR的ICC在0.925 ～0.946之间,相关性优于应用苦味酸法测定肌酐.Bland-Altman图显示,各方程评估的eGFR在高值区偏差较大,但用酶法时偏离程度均小于应用苦味酸法.在rGFR≥60 ml·min-1·(1.73 m2)-1时,各方程应用酶法测定肌酐时的30％准确性在68.3％～90.0％之间,应用苦味酸法30％准确性在41％～75％之间,除课题组方程1外,其他方程应用酶法测定肌酐时的准确性均显著高于苦味酸法.而rGFR＜60ml· min-1·(1.73 m2)-1时,应用酶法、苦味酸法测定肌酐的30％准确性分别在39.7％～49.1％、40.5％～52.6％之间.对于同一方程,应用酶法测定肌酐的两套不同检测系统间,其30％准确性差异无统计学意义,而应用苦味酸法的两套不同检测系统间,其30％准确性差异有统计学意义.结论 同一评估方程使用苦味酸法和酶法两种不同的肌酐检测方法时,结果存在显著性差异.采用酶法测定肌酐时,方程评估的eGFR结果在相关性、偏离程度、准确性方面均优于苦味酸法.     

两种不同方法检测血清肌酐结果的比较

目的探讨苦味酸法和酶法检测血清肌酐水平的差异。方法用酶法和苦味酸法分别检测136份血清标本肌酐的水平,以酶法检测的值分为四组。结果1组苦味酸法值高于酶法值(P<0.01);2、3组两种方法测得值基本相符(P>0.05);4组苦味酸法值低于酶法值(P<0.01)。结论苦味酸法适应范围窄,干扰多;酶法适应范围宽,特异性强,干扰小。不同测定方法应建立不同参考值。     

酶法与苦味酸法测定血清肌酐差异的Meta分析

目的 采用Meta分析的方法比较酶法与苦味酸法对血清肌酐在不同水平段的测定差异.方法 计算机检索中国期刊全文专题数据库、万方电子期刊、中国科技期刊数据库所收录的在国内发表的有关酶法与苦味酸法测定血清肌酐对照研究的文章,采用RevMan5软件对符合条件的文献进行分析.结果 共有9篇文献纳入本次研究,包含有2545例患者的血清样本,依血清肌酐水平,将数据分为低（＜130μ mol/L）、中（130～500 μmol/L）、高（＞500μmo]/L）三组.当血清肌酐浓度低于130 μmol/L时,酶法所测血清肌酐值小于苦味酸法测定结果[WMD=-29.44,95％ CI（-32.76,-26.13）],当血清肌酐浓度介于130～ 500 μmol/L时,酶法所测血清肌酐值小于苦味酸法测定结果[WMD=-11.80,95％CI（-19.09,-4.52）],当血清肌酐浓度高于500 μmol/L时,酶法所测血清肌酐值大于苦味酸法测定结果[WMD=31.88,95％ CI（11.44,52.32）].结论 根据目前证据可认为：当血清肌酐浓度低于500 μmol/L时,酶法测定结果低于苦味酸法;当血清肌酐浓度高于500 μmol/L时,酶法测定结果高于苦味酸法.     

Use of robust ZB and ZW to evaluate proficiency testing data

BackgroundIn PT program, mean is conventionally used as the target after deletion of values which exceed the mean ± 3SD. This computation fails if there are some outliers.MethodsCreatinine data were divided into Jaffe and enzymatic method groups in accordance with the analytical method used. The results tested by both methods were compared. The normality of standardized sum and difference was tested. The outliers in these data were deleted. The trimmed data were tested for normality. The performance of laboratories was assessed using ZB and ZW, whose values were considered acceptable when |ZB| or |ZW|≤2, questionable when 2<|ZB|<3 or 2<|ZW|<3 and unacceptable when |ZB| or |ZW|≥3.ResultsThe results tested using Jaffe and enzymatic methods were not comparable. The data of standardized sum and difference were not normally distributed. When the outliers in these data were removed, the trimmed data were normally distributed. In Jaffe group, the acceptable rates of between and within laboratories respectively were 90.2% and 86.0%. In enzymatic group, the acceptable rates of between and within laboratories respectively were 82.6% and 82.4%.ConclusionIt was reasonable to choose robust ZB and ZW as assessment indexes because robust z-scores were less influenced by outliers.     

Robust and traditional statistical methods in the establishment of immunoglobulin E target values in external quality assessment program

BACKGROUND: In an EQA scheme, peer group mean is conventionally regarded as the target after removing values exceeding the mean+/-3SD. However, this computation fails if there are some outliers. METHODS: The outliers in each original data set were separately deleted by traditional and robust statistical methods. The data distributions of original and trimmed data sets were separately tested by Shapiro-Wilks or Kolmogorov-Smirnov Z test. The means of peer groups were used to set IgE targets. The difference between targets set by both methods was tested by 1-sample t test. RESULTS: The original data sets were not all Gaussian distributed. After deletion of outliers using robust statistical method, the modified data sets of all tested groups were normally distributed. IgE targets established by robust and traditional methods were significantly different in some groups. The incompatible IgE targets derived all from the original and trimmed data sets which were not Gaussian distributed. CONCLUSIONS: The premise for choosing a traditional method to delete outliers and using peer group means as targets was that the data sets must be Gaussian distributed. The reasons that caused the targets to be incompatible possibly were the 2 rules to be broken. Robust statistical method was used for deletion of outliers due to the distorted distribution.     

Compensating for the influence of total serum protein in the Schwartz formula

Abstract Background: The Schwartz 2009 creatinine-based revised formula is the only pediatric GFR estimating formula, which is compatible with the recent global creatinine standardization. This formula is only applicable if enzymatic creatinine methods are used. We propose an equation, taking into account the relative bias caused by serum proteins to use Jaffe based creatinine data for GFR estimation. Methods: In a cohort study of 100 pediatric patients, serum creatinine was measured using a kinetic rate-blanked Jaffe assay (modified kinetic alkaline picrate method), a kinetic rate-blanked Jaffe compensated assay for reactive proteins and an enzymatic assay (creatinine plus method). Serum total protein, albumin, urea, uric acid and total bilirubin were measured with the use of commercial agents. Results: The difference in serum creatinine between the enzymatic method and the compensated Jaffe method was mainly dependent on the total protein concentration in serum (r2=0.61, p<0.001). After applying the proposed protein correction, corrected compensated Jaffe results and creatinine clearance values became interchangeable with enzymatic serum creatinine results (r2=0.99, p<0.001; Deming regression: slope: 0.9787, intercept: -0.351) and with the newly proposed Schwartz formula, respectively (r2=0.99, p<0.001; Deming regression: slope 1.004, intercept: 2.16). Conclusions: In this study, we demonstrated the usability of the alkaline picrate method in the Schwartz formula, taking into account the relative bias caused by serum proteins.     

应用六西格玛管理方法评估糖化血红蛋白检测系统性能

目的 用六西格玛（6σ）管理方法评估糖化血红蛋白检测系统性能,用以指导质量改进.方法 选取2013年同时参加室间质量评价（EQA）计划和室内质量控制室间比对计划的实验室,共327家,包含全国30个省、直辖市、自治区.由EQA结果和室内质控,分别获得各实验室的偏倚（bias）和变异系数（Cv）,并依据2013年卫生部临床检验中心糖化血红蛋白室间质评给出的允许总误差（TEa）标准,按照公式σ=（TEa-bias）/CV计算σ值,评价各实验室的糖化血红蛋白检测系统性能;分别对实验室检测系统的偏倚和不精密度进行评价,计算满足标准的比例.结果 能达到3σ水平（3σ）的实验室为65.1％（213/327）,达到6σ水平的实验室占26.9％（88/327）.按分析系统分组后,不同组别可接受σ水平比率不同,范围在33.3％～86.7％.各系统满足偏倚标准的比例为75.0％～100％,满足不精密度标准的比例在40.0％～100％之间.结论 大部分实验室糖化血红蛋白测定质量水平可靠,有小部分实验室的检测质量特别是精密度还有改进余地;6σ质量管理是临床实验室质量控制的一项有效管理工具,有助于实验室不断提高临床检测水平.     

常见肌酐测定方法中存在的干扰

目的 探讨目前常见肌酐测定方法中存在干扰。方法 以漂白土（fuller's earth)吸附法为标准，对Jaffe'氏反应速率法、紫外法、比色 和电极法进行方法学评价。结果 在所采用的8种干扰物（丙酮酸钠、α －酮戊二酸、胆红素、血红蛋白、肌酸、多巴胺、抗坏酸、地塞米松）中，Jaffe'氏反应速率法受干扰物影响最大，α－酮戊二酸（≥0.82mmol/L)、丙酮酸钠（≥0.186mmol/L)对该法有正干扰，而胆红素（≥165.5umol/L）则有明显负干扰。紫外法基本不受干扰物影响；比色法不仅受肌酸（≥0.21umol/L）的正干扰，而且也受多巴胺（≥0.28mmol/L)的负干扰；电极法仅受到肌酸（≥0.62 mmol/L）的正干扰。结论 紫外法是目前测定肌酐最好的方法。     

Calculating effect size for continuous variables: D537--a robust, quantile-based approach

The calculation of effect size is an important step in measuring the potential real-life significance of the effect of an intervention. In the case of continuous data, Cohen's d is frequently used. This scales the difference between the means of two groups, or the mean difference between pairs of measurements, by dividing by the standard deviation. However, outlying values, especially in small studies, can influence the size of d. This article presents D537, a robust formula for d that is based on rank statistics. The median is used as a measure of difference, while the scaling factor is the range between the 30th and 70th percentiles of the distribution; a range that is equal to one standard deviation when the data are normally distributed. When data are normally distributed, the value of D537 is equal to that of Cohen's d. As D537 is based on the 30th, 50th and 70th percentiles, it is robust to outliers.     

Comparison between IDMS-traceable Jaffe and enzymatic creatinine assays for estimation of glomerular filtration rate by the CKD-EPI equation in healthy and diabetic subjects

Objectives

The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals.

Design and methods

Cross-sectional study conducted in 123 adult southern Brazilians with GFR > 60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49 ± 16 years (range of 19–86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method.

Results

Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79 ± 0.16 vs. 0.79 ± 0.15 mg/dL, respectively, P = 0.76), and diabetic patients (0.96 ± 0.22 vs. 0.92 ± 0.29 mg/dL, respectively, P = 0.17). However, the correlation between the two methods was higher in the healthy group (r = 0.90 vs. 0.76, P < 0.001). The difference between Jaffe creatinine and enzymatic creatinine was < 10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P = 0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results.

Conclusion

Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better.     

Evaluation of the IRMA TRUpoint and i-STAT creatinine assays

BACKGROUND: The i-STAT (Abbott Diagnostics, East Windsor, NJ) and IRMA TRUpoint (ITC, Edison, NJ) POCT analyzers were evaluated in an oncology center. METHODS: Precision and agreement with our core laboratory creatinine was judged by comparison of 50 consecutive chemotherapy patient results against the Roche rate-blanked Jaffe and enzymatic creatinine methods. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault (CG) calculation and Modification of Diet in Renal Disease Study (MDRD) equation. RESULTS: Precision varied from 1% (enzymatic)-6.1% (TRUpoint). Correlation was good (r>0.9948) with slopes within 5% of the Jaffe and enzymatic methods. Intercepts were <15.9 micromol/l (<0.18 mg/dl), and statistically significant bias (p<0.0025) was noted between the mean of patient specimens for i-STAT correlations to both the Jaffe and enzymatic laboratory creatinine methods. There was statistically significant concordance of estimated GFR between all methods, however, the agreement of estimated GFR to either the Jaffe or enzymatic creatinine laboratory methods was better for the TRUpoint (by either MDRD or CG estimation) and i-STAT (by MDRD equation) (Kappa>0.60) than the i-STAT (by CG estimation) (Kappa=0.41-0.60). CONCLUSION: Small biases in the calibration of analytical creatinine methods can lead to differences in clinical concordance using estimated GFR. Selecting an optimal POCT method depends on the institution's current creatinine method and tolerance for analytical performance and clinical concordance.     

CALIPER paediatric reference intervals for the urea creatinine ratio in healthy children & adolescents

BackgroundThe urea creatinine ratio (UCR) is important in the clinical assessment of several medical conditions, including acute kidney injury and gastrointestinal bleeding. However, accurate and robust paediatric reference intervals (RIs) for this ratio have not been well established. Here, we determined age- and sex-specific discrete and continuous RIs for UCR in the Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents for the first time.MethodsUCR was calculated for approximately 1030 CALIPER participants using retrospective urea and creatinine (both Jaffe and enzymatic methods) normative data. Partitions were determined using the Harris & Boyd statistical method. Discrete RIs were established in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Continuous RIs were established using nonparametric quantile regression.ResultsSeveral age- and sex-specific partitions were necessary to capture dynamic physiological trends associated with this ratio throughout childhood and adolescence, highlighting the benefit of continuous RI establishment. Established UCR RIs also demonstrated marked differences between Jaffe and enzymatic assay methods.ConclusionOur results clearly demonstrate the critical need for RI stratification by important covariates such as age, sex, and creatinine assay methodology for paediatric UCR test result interpretation. These data contribute to our understanding of normative UCR values in childhood and adolescence and can be expected to improve paediatric test result interpretation in clinical laboratories that report this ratio.