VITEK-2 Compact仪器法检测葡萄球菌属克林霉素诱导性耐药的评价

目的 评价VITEK-2 Compact仪器法检测葡萄球菌属克林霉素诱导性耐药的应用价值.方法 分别采用VITEK-2 Compact仪器法和D试验检测83株金黄色葡萄球菌,52株凝固酶阴性葡萄球菌属的诱导性克林霉素耐药,两种方法的比较采用卡方检验,同时以“D试验”为金标准,计算VITEK-2 Compact仪器法的特异性、敏感性、假阳性率、假阴性率.结果 经卡方检验,两种方法在检测金黄色葡萄球菌克林霉素诱导性耐药方面具有很好的一致性,特异性为100.0％,敏感性为95.8％,kappa值为0.97,假阴性率为4.2％;两种方法在检测凝固酶阴性葡萄球菌方面结果一致性较好,特异性、敏感性分别为83.3％、100.0％,kappa值为0.435,假阳性率为16.7％.结论VITEK-2 Compact仪器法在检测金黄色葡萄球菌诱导性克林霉素耐药方面与D试验有很好的一致性,但存在假阴性可能;在检测凝固酶阴性葡萄球菌属细菌方面,与D试验有较好的一致性,存在一定的假阳性.     

Evaluation of five immunodiagnostic techniques in echinococcosis patients

Double diffusion (DD), indirect haemagglutination (IHA), immunoelectrophoresis (IEP), latex agglutination (LA), and complement fixation (CF) tests were evaluated for sensitivity and specificity in the diagnosis of 141 surgically-proven Turkana echinococcosis patients and 10 controls. The overall sensitivities for the tests were: IHA, 86.7%; LA, 53.3%; CF, 63.3%; DD, 55.0%; IEP, 55.0%. LA and CF tests produced a high number of false positive results; IHA gave a false positive result in 10% of cases; no false positives were obtained with IEP and DD. A combination of the latter three tests would therefore offer the best chance of detecting specific anti-Echinococcus antibodies, with an average sensitivity of 62.7%. The possible reasons for the relatively high incidence of false negative values are discussed.     

不同方法检测正常人群血清甲胎蛋白比较

目的：对甲胎蛋白（AFP）酶联免疫吸附试验法与甲胎蛋白化学发光法两种检测方法的敏感性和特异性进行对比,评价两种方法在正常人群中甲胎蛋白检测的应用效果。方法：用酶联免疫吸附试验法与化学发光法同时对2000份体检血清标本甲胎蛋白进行检测。结果：用酶联免疫吸附试验法检测出20例甲胎蛋白阳性标本,用化学发光法检测甲胎蛋白21例高于正常范围,化学发光法检出AFP高于正常范围的21例中,阳性率1．05％,经确证AFP高于正常范围的21例,均为阳性;酶联法检出20例阳性,阳性率1．15％,1例经确证为阴性,特异性为95％。两种方法同为阳性的20例标本,经确证均为阳性。结论：在正常体检甲胎蛋白人群中,酶联免疫吸附试验法与化学发光法检测AFP敏感性差别不大,而特异性差别较大,甲胎蛋白酶联免疫吸附试验法更适合于血液的甲胎蛋白筛查。甲胎蛋白筛查阳性的标本再用化学发光法定量检测AFP,可保证排除AFP假阳性。     

A simple decision analytic solution to the comparison of two binary diagnostic tests

One of the most basic biostatistical problems is the comparison of two binary diagnostic tests. Commonly, one test will have greater sensitivity, and the other greater specificity. In this case, the choice of the optimal test generally requires a qualitative judgment as to whether gains in sensitivity are offset by losses in specificity. Here, we propose a simple decision analytic solution in which sensitivity and specificity are weighted by an intuitive parameter, the threshold probability of disease at which a patient will opt for treatment. This gives a net benefit that can be used to determine which of two diagnostic tests will give better clinical results at a given threshold probability and whether either is superior to the strategy of assuming that all or no patients have disease. We derive a simple formula for the relative diagnostic value, which is the difference in sensitivities of two tests divided by the difference in the specificities. We show that multiplying relative diagnostic value by the odds at the prevalence gives the odds of the threshold probability below which the more sensitive test is preferable and above which the more specific test should be chosen. The methodology is easily extended to incorporate combinations of tests and the risk or side effects of a test. Copyright © 2012 John Wiley & Sons, Ltd.     

Confidence intervals for post-test probability

Confidence intervals are a natural way to describe the uncertainty of post-test probability in diagnostic tests. We consider confidence intervals for two different scenarios. At a site, for example, hospital emergency room or student health centre, with measured values of disease prevalence, sensitivity and specificity available, the confidence interval is similar to results in the literature, but at a site where measured values of these indices are unavailable, we develop a method, using the values of disease prevalence, sensitivity and specificity from other sites, to obtain a confidence interval for post-test probability. We use the diagnosis of strep throat to illustrate the results. We also obtain confidence intervals from simulations to compare with the results of both scenarios.     

The increased availability of self-tests for medical analyses

A marked increase in the availability of diagnostic tests for use at home has been observed in recent years. There are regulations concerning the development and application of these tests. The question whether the increased use of self-tests is a positive or negative development cannot be answered easily. In some cases serious diseases may be detected in people who are reluctant to consult a physician. In other cases false negative test results may delay necessary treatment. Further exploration of the use, sensitivity, specificity, benefits and harms of specific tests is warranted.     

Systematic evaluation and comparison of statistical tests for publication bias

BACKGROUND: This study evaluates the statistical and discriminatory powers of three statistical test methods (Begg's, Egger's, and Macaskill's) to detect publication bias in meta-analyses. METHODS: The data sources were 130 reviews from the Cochrane Database of Systematic Reviews 2002 issue, which considered a binary endpoint and contained 10 or more individual studies. Funnel plots with observers'agreements were selected as a reference standard. We evaluated a trade-off between sensitivity and specificity by varying cut-off p-values, power of statistical tests given fixed false positive rates, and area under the receiver operating characteristic curve. RESULTS: In 36 reviews, 733 original studies evaluated 2,874,006 subjects. The number of trials included in each ranged from 10 to 70 (median 14.5). Given that the false positive rate was 0.1, the sensitivity of Egger's method was 0.93, and was larger than that of Begg's method (0.86) and Macaskill's method (0.43). The sensitivities of three statistical tests increased as the cut-off p-values increased without a substantial decrement of specificities. The area under the ROC curve of Egger's method was 0.955 (95% confidence interval, 0.889-1.000) and was not different from that of Begg's method (area=0.913, p=0.2302), but it was larger than that of Macaskill's method (area=0.719, p=0.0116). CONCLUSION: Egger's linear regression method and Begg's method had stronger statistical and discriminatory powers than Macaskill's method for detecting publication bias given the same type I error level. The power of these methods could be improved by increasing the cut-off p-value without a substantial increment of false positive rate.     

Assessing the gain in diagnostic performance when combining two diagnostic tests

Combining dichotomous (or dichotomized) results of two diagnostic tests will result in a trade-off in sensitivity and specificity of the combined test relative to the component tests. Because of this inherent trade-off, likelihood ratios provide a clinically relevant means of comparing the combined test with one of its components. The likelihood ratios depend on both sensitivity and specificity and hence take into account the trade-off between them. A graphical approach is used to assess whether the combined test is superior to a component test, or vice versa. Asymptotic standard errors are derived for comparing likelihood ratios when a paired study design is used. The trade-off in the expected number of additional true positive and false positive results (or true negative and false negative results) is used as the basis for deciding whether to use tests in combination when neither the combined nor a component test shows superior test performance based on their likelihood ratios. These methods are illustrated with an example that considers the combined use of Pap and HPV testing.     

O1群霍乱弧菌胶体金法快速检测

目的 了解胶体金法检测O1群霍乱弧菌的特异性、灵敏度和实用性。方法 取患者粪便标本,先用碱性蛋白胨水35℃增菌6h,然后用胶体金法进行检测,同时作霍乱弧菌常规培养,培养出细菌后用血清凝集法作为鉴别诊断O1群霍乱弧菌的金标准,用统计学方法对胶体金法诊断试验的评价指标进行计算。结果 700份样本中,常规法培养出O1霍乱弧菌105株,胶体金法试验阳性108株,经χ²检验,差异无统计学意义(χ²=0.24,P>0.05),表明胶体金法检测O1群霍乱弧菌与常规培养法检测结果之间的差异无统计学意义。胶体金法检测O1群霍乱弧菌诊断试验的灵敏度为93.33%,特异性为98.32%,阳性预测值为90.74%,阴性预测值为97.18%,假阴性率为1.68%,假阳性率为6.67%。结论 胶体金法检测O1群霍乱弧菌特异性高(98.32%),灵敏度好,与常规培养法的一致性也较高,在快速检测O1群霍乱弧菌中有一定应用价值。     

On simultaneous assessment of sensitivity and specificity when combining two diagnostic tests

Diagnostic tests are seldom adopted in isolation. Few tests have high sensitivity and specificity simultaneously. In these cases, one can increase either the sensitivity or the specificity by combining two component tests under either the 'either positive' rule or the 'both positive' rule. However, there is a tradeoff between sensitivity and specificity when these rules are applied. We propose three statistical procedures to simultaneously assess the sensitivity and specificity when combining two component tests. Measurements of interest include rate difference and rate ratio. Our empirical results demonstrate that (i) the asymptotic test procedures for both measurements and approximate test procedure for rate difference possess inflated type I error rate; (ii) the exact test procedures for both measurements possess deflated type I error rate; and (iii) the approximate (unconditional) test procedure for rate ratio becomes an reliable alternative and nicely controls the actual type I error rate in small to moderate sample sizes. Moreover, the approximate (unconditional) test procedure is computationally less intensive than the exact (unconditional) test procedure. We illustrate our methodologies with a real example from a residual nasopharyngeal carcinoma (RNP) study.     

The effect of misclassification of disease status in follow-up studies: implications for selecting disease classification criteria

For many diseases, a set of diagnostic criteria with perfect sensitivity and specificity does not exist. In the design of a follow-up study of such a disease, one often has a choice between using a set of narrow classification criteria for the disease outcome (i.e., a test with relatively high specificity and relatively low sensitivity) or a broader set of criteria (i.e., a more sensitive, less specific test). A model was investigated which simulated choices one may have between disease classification tests, to determine how the required sample size and bias in the estimates of the risk ratio and risk difference varied between tests. A two-sample study with nondifferential misclassification of disease outcome was assumed. Based on the model, the bias in the risk ratio increases as one increases the sensitivity of the diagnostic test at the expense of specificity. Conversely, the bias in the risk difference decreases with increasing sensitivity and declining specificity. The required sample size is minimized at relatively high sensitivity and relatively low specificity. Selection of the disease classification test as that at which the required sample size is minimized could reduce some of the large data collection costs of follow-up studies. The advantages and limitations of applying this technique to actual studies are discussed.     

Statistical methods for the meta-analysis of diagnostic tests must take into account the use of surrogate standards

BackgroundEvaluating the performance of a new diagnostic test presents a challenge if the conventional “gold” standard is invasive, hazardous, or expensive, especially if that test has been supplanted in usual clinical practice by a “silver” standard test that is more acceptable and perhaps only slightly suboptimal. In such a case, a systematic literature review will typically uncover a mix of study types, some using the gold and some the silver.ObjectiveWe sought to develop and compare statistical methods to account for this kind of heterogeneity in performing a meta-analysis.Study Design and SettingWe compared the performance of estimation methods based on generalized mixed models which incorporate heterogeneity, especially choice of reference test, and random between-study variation in sensitivity and specificity with more conventional methods which neglect the differences in reference tests. Computer simulations were conducted to assess bias and root mean square error of point estimates and coverage of interval estimates.ResultsMethods ignoring the difference in reference tests severely underestimated sensitivity and specificity under the assumption of conditional independence. Bias was substantial even for references with small departure from the standard and persisted with increasing sample size. Coverage of interval estimates was far from nominal level.ConclusionIn the presence of varying reference tests, avoidance of bias and invalid confidence intervals for diagnostic performance requires applying a model that accounts for differences in reference test and heterogeneity among studies.     

A new whole-scolex complement-fixation test for hydatid disease

The sensitivity of indirect agglutination tests for the diagnosis of human hydatid disease, although high, is not sufficient. Furthermore, the general use of hydatid fluid as antigen is responsible for some false positive reactions. Scolex extracts have been shown to increase specificity, but less attention has been paid to whole-scolex antigens. The author describes a new whole-scolex complement-fixation test that, like other scolex tests, is more specific than tests using fluid antigen. Its sensitivity is at least equal to that of the hydatid fluid latex-agglutination test, and is higher than that of the fluorescent-antibody, the scolex extract latex, and the hydatid fluid complement-fixation tests.     

Evaluation of a dual-antigen ELISA test for the serodiagnosis of tuberculosis

Two antigen preparations from Mycobacterium tuberculosis and M. bovis, respectively, were used in an enzyme-linked immunosorbent assay (ELISA) to quantitate the level of IgG antibodies in samples of 169 sera obtained in India from 75 patients with pulmonary tuberculosis and from 94 controls. The results of the two ELISA tests were integrated using defined criteria. All the controls were correctly classified by this dual-ELISA approach and only two patients were categorized as false negatives. The method has a specificity of 1.00 and a sensitivity of 0.974, while the gain in the certainty of diagnosis was 1.974, only slightly less than the ideal value of 2.00.     

Methods for assessing the accuracy of PCR-based tests: comparisons and extensions

Polymerase chain reaction (PCR) based tests are commonly used to diagnose various infections. Such tests are assumed to be highly 'sensitive', however, no consensus definition of, or method for estimating, sensitivity exists. Hughes and Totten proposed that sensitivity be defined as a function of the number of target DNA molecules in the sample with specificity corresponding to the case where there is no target DNA molecule present. They then developed parametric, non-parametric and semi-parametric models for estimating the sensitivity curve. In this paper a general model is proposed that yields their three models as special cases when specificity is assumed to be 1.0. We also extend the general model to incorporate covariates. Simulation studies are used to compare the different estimators. The methods are applied to data from a PCR-based test for Mycoplasma genitalium.     

两种细胞学检查联合HPV检测筛查宫颈癌及癌前病变的临床对比分析

目的:对比分析液基薄层细胞学检查(TCT)联合HPV检测和巴氏涂片检查联合HPV检测筛查早期宫颈癌和癌前病变的效果。方法:选择妇科体检的1 012例女性随机分成两组:TCT组500例实施液基薄层联合HPV检测;巴氏涂片检查组512例进行巴氏涂片检查联合HPV检测,比较两种方法对于宫颈异常的检出率,两种方法都以病理检查为标准。结果:TCT组特异性为79.22%、敏感性为92.87%、假阴性率为0.20%;巴氏涂片组特异性为98.24%、敏感性为56.24%、假阴性率为1.97%,两组比较差异有统计学意义(P<0.05)。阳性检出率TCT组为3.40%,巴氏涂片组为2.73%,两组比较差异无统计学意义(P>0.05)。结论:在宫颈癌和癌前病变诊断中,TCT检查联合HPV检测优于巴氏涂片检查联合HPV检测,其筛查的假阴性率较低,敏感性较高,可以作为一种先进的筛查方法。     

New confidence intervals for the difference between two sensitivities at a fixed level of specificity

For two continuous-scale diagnostic tests, it is of interest to compare their sensitivities at a predetermined level of specificity. In this paper, we propose three new intervals for the difference between two sensitivities at a fixed level of specificity. These intervals are easy to compute. We also conduct simulation studies to compare the relative performance of the new intervals with the existing normal- approximation-based interval proposed by Wieand et al. Our simulation results show that the newly proposed intervals perform better than the existing normal-approximation-based interval in terms of coverage accuracy and interval length.     

A randomized crossover trial of PAPNET for primary cervical screening

OBJECTIVE: To develop and demonstrate efficient methods to estimate the relative true positive and false positive rates of two cervical screening tests (conventional cytology and PAPNET). METHODS: We designed the study to meet stringent methodologic criteria for comparison of two tests while simultaneously minimizing the numbers requiring reference standard verification. We used a cytology reference standard and also assessed histology when available. For the primary analysis, slides with discordant results around the test threshold (CIN 1) were reviewed by a panel of two cytopathologists, blind to previous results, to establish the reference standard result (reference standard threshold for abnormality CIN2). Where histology was available, a secondary analysis was conducted with the reference standard based on the highest grade lesion (either cytology or histology). RESULTS: Among 21,747 Pap smears, 372 were discordant around the test threshold, requiring verification. In the primary analysis PAPNET detected four more true positives than conventional reading; difference in sensitivity 1.29% (95%CI -5.79 to 8.36%, P=.40). There were two extra false positives using PAPNET; difference in the false positive rate 0.0097% (95%CI -0.122 to 0.142%, P=.47). The results of the combined cytology and histology analysis were similar; difference in true positive rate 0.29% (95%CI -6.76 to 7.34%, P=.50) and difference in false positive rate 0.024% (95%CI -0.098 to 0.15%, P=.39). CONCLUSION: This is an efficient and valid study design where the objective is to examine the comparative accuracy of two tests. The design provides an efficient means of estimating the difference between true positive and false positive detection by the two tests, which often is sufficient information for policy decisions.     

Syphilis and blood donors: Comparison of two different diagnostic strategies

In this study the validity of the methods provided for by Italian law (VDRL or RPR tests) were compared with the diagnostic strategy suggested by WHO (the use of VDRL and TPHA tests in parallel). Sensitivity, specificity and posterior probability of infection after a positive or a negative result were estimated. The application of two tests in parallel produces a statistically significant increase of sensitivity from 47% to 98% while the increase of proportion of false positives is not significant (from 15% to 16%). Probability of infection when the result is negative to the RPR is 0.07%o while a negative result to the RPR and the TPHA tests has a probability to be really infected of 0.003%o. The use of the two tests (RPR and TPHA) in parallel is able to give the highest degree of sensitivity, indispensable to select possible blood donors, while maintaining a good degree of specificity. The authors concluded that the use of VDRL alone does not exclude infectivity of a blood sample, and in accordance with WHO and international recommendations, the VDRL or RPR and TPHA tests should be used in parallel for syphilis screening.     

免疫层析法与酶联免疫吸附法检测血中HBsAg、抗-HCV、抗-HIV的比较

〔目的〕分析比较乙型肝炎表面抗原(HBsAg)、丙型肝炎病毒抗体(抗-HCV)、HIV抗体(抗-HIV)的免疫层析快速试剂在实际应用中的灵敏度、特异度和准确度,为今后的工作提供参考。〔方法〕对502份健康体检血清标本同时用快速免疫层析法和酶联免疫吸附法(ELISA)检测HBsAg、抗-HCV、抗-HIV,对其灵敏度和特异度进行比较。〔结果〕与ELISA相比,502份血清标本中HBsAg金标法有2份假阴性,5份假阳性,灵敏度为99.6%,特异度为99.0%,准确度为98.6%;抗-HCV金标法无假阴性,有9份假阳性,灵敏度为100%,特异度为98.2%,准确度为98.2%;抗-HIV硒标法有2份假阳性,灵敏度为100%,特异度为99.6%,准确度为99.6%。〔结论〕金标法检测HBsAg灵敏度和特异度稍低于ELISA,有漏检和误检现象,而抗-HCV、抗-HIV快速法与ELISA比较灵敏度相当,而特异度稍低,因此,都要结合ELISA结果才可出具最终检测报告,抗-HIV的检测任何一种方法出现阳性时都要进行确认试验。