[Abolishment of the categories of discrepancy between diagnoses is a time dictate].

By taking into account the fact that the percentage and category of a diagnosis discrepancy (DD) are used as one of the criteria of the health care quality control system, rather than used to set up a quality management system, it becomes more evident that we should agree to the proposal by Prof. I. A. Kazantseva that it is inexpedient to use DD categories, which simultaneously excludes them from the criteria for assessing the quality of health care delivered in the therapeutic-and-prophylactic institutions. For this, Appendix No. 7 to the 4 April, 1983 Order No. 375 "On further improvement of postmortem service in the country" in the part concerning the grouping of DD into categories should be officially recognized invalid. The pathologist's duty should be to state "coincidence" or "discrepancy" of diagnosis and the KILI, LKK, or KEK should elucidate reasons for DD as done at the Moscow Regional Research Clinical Institute, with the further reflection being given in the autopsy protocol.

[Matters of identifying the categories of discrepancy between diagnoses as a part of the problem of organizing the clinical expert work of a postmortem service].

Whether the categories of a discrepancy between diagnoses should not be identified, which has been put by I. A. Kazantseva, is supported by the Society of Pathologists. The ranking of diagnostic discrepancies has been already subject to criticism in a number of standard guidance publications. However, this matter is a part of the unsolved problem of the clinical expert work of a postmortem service. Many regions have elaborated and approved their own principles of its organization. The standards of the Russian Agency are the most important achievement in assuring orderliness of its work. The problem requires further initiatives of the Russian Society of Pathologists and its close interaction with the Ministry of Health and Social Development in approving the relevant normative documents as soon as possible.

Exploring the iceberg of errors in laboratory medicine.

The last few decades have seen a significant decrease in the rates of analytical errors in clinical laboratories, and currently available evidence demonstrates that the pre- and post-analytical steps of the total testing process (TTP) are more error-prone than the analytical phase. In particular, most errors are identified in pre-pre-analytic and post-post analytic steps outside the walls of the laboratory, and beyond its control. However, in a patient-centered approach to the delivery of health care services, there is the need to investigate any possible defect in the total testing process that may have a negative impact on the patient. In fact, in the interests of patients, any direct or indirect negative consequence related to a laboratory test must be considered, irrespective of which step is involved and whether the error is caused by a laboratory professional (e.g., calibration or testing error) or by a non-laboratory operator (e.g., inappropriate test request, error in patient identification and/or blood collection). Data on diagnostic errors in primary care and in the emergency department setting demonstrate that inappropriate test requesting and incorrect interpretation account for a large percentage of total errors whatever the discipline involved, be it radiology, pathology or laboratory medicine. Patient misidentification and problems in communicating results, which affect the delivery of all diagnostic services, are widely recognized as the main goals for quality improvement. Therefore, some common problems affect diagnostic errors, although specific faults characterising errors in laboratory medicine should lead to preventive and corrective actions if evidence-based quality indicators are developed, implemented and monitored. The lesson we have learned is that each practice must examine its own total testing process to discover its weaknesses and identify appropriate remedies.

The causes of misdiagnosis and adverse outcomes in PGD.

The European Society of Human Reproduction and Embryology PGD Consortium has collected data on PGD cycles and deliveries since 1997. From 15,158 cycles, 24 misdiagnoses and adverse outcomes have been reported; 12/2538 cycles after polymerase chain reaction and 12/12,620 cycles after fluorescence in situ hybridization. The causes of misdiagnosis include confusion of embryo and cell number, transfer of the wrong embryo, maternal or paternal contamination, allele dropout, use of incorrect and inappropriate probes or primers, probe or primer failure and chromosomal mosaicism. Unprotected sex has been mentioned as a cause of adverse outcome not related to technical and human errors. The majority of these causes can be prevented by using robust diagnostic methods within laboratories working to appropriate quality standards. However, diagnosis from a single cell remains a technically challenging procedure, and the risk of misdiagnosis cannot be eliminated.

Causes, consequences, detection, and prevention of identification errors in laboratory diagnostics.

Laboratory diagnostics, a pivotal part of clinical decision making, is no safer than other areas of healthcare, with most errors occurring in the manually intensive preanalytical process. Patient misidentification errors are potentially associated with the worst clinical outcome due to the potential for misdiagnosis and inappropriate therapy. While it is misleadingly assumed that identification errors occur at a low frequency in clinical laboratories, misidentification of general laboratory specimens is around 1% and can produce serious harm to patients, when not promptly detected. This article focuses on this challenging issue, providing an overview on the prevalence and leading causes of identification errors, analyzing the potential adverse consequences, and providing tentative guidelines for detection and prevention based on direct-positive identification, the use of information technology for data entry, automated systems for patient identification and specimen labeling, two or more identifiers during sample collection and delta check technology to identify significant variance of results from historical values. Once misidentification is detected, rejection and recollection is the most suitable approach to manage the specimen.

Monoplex LightCycler polymerase chain reaction quantitation of the HER2 gene for quality assurance of HER2/neu testing by immunohistochemistry and fluorescence in situ hybridization.

BACKGROUND: Assessment of HER2 by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) is a standard practice for breast carcinomas. Testing is associated with a 20% disagreement between laboratories. The College of American Pathologists (CAP) guidelines for HER2 testing include validation of HER2 test methods by achieving 95% concordance with another validated method. Our laboratory requires IHC 3+ FISH nonamplified specimens to undergo retesting by polymerase chain reaction (PCR). A random sample of IHC 2+ cases are routinely tested by PCR. We found this practice useful for resolving discrepancies in HER2 testing. METHODS: At clinician request, seventy-nine 3+ and one hundred forty-eight 2+ cases were tested by FISH. In 22 cases, IHC was 3+ but FISH was nonamplified. These 22 cases underwent HER2 LightCycler monoplex polymerase chain reaction (MPCR) testing. Seventeen 2+ nonamplified cases were tested by MPCR. RESULTS: Twenty-one 3+, FISH nonamplified cases were found to be MPCR nonamplified. One IHC 3+, FISH nonamplified case was MPCR amplified. Seventeen 2+, FISH nonamplified cases were MPCR nonamplified. In all but one case, FISH and MPCR were concordant. DISCUSSION: American Society of Clinical Oncology/CAP guidelines propose validation of testing procedures by showing 95% concordance with a validated test for positive and negative assays. Specific actions are not recommended to resolve discordances between tests. Our laboratory uses 3 different modalities for HER2 testing. We have found that our 2 methods for testing gene amplification status show a higher degree of concordance between themselves than either did with IHC. Review of the 3+ IHC nonamplified cases showed them to have a dark, granular circumferential staining pattern.

Applying case definition criteria to irritable bowel syndrome.

OBJECTIVE: The quality of documentation of signs and symptoms and validation of the diagnosis of irritable bowel syndrome (IBS) according to case definition criteria of Manning, Rome I and Rome II in an office setting has not been previously described. We sought to identify and validate cases of IBS based on the Manning, Rome I and Rome II diagnostic criteria in a rural practice setting. SETTING: Marshfield Epidemiologic Study Area (MESA) Central consisting of 14 ZIP codes in central Wisconsin, USA. METHODS: A retrospective cohort study involved 890 patients with the diagnostic codes 564.1 for irritable bowel syndrome and 306.4 spastic colon-psychogenic who had presented to the practice from 1993-2003. Duration, frequency, concordance and intensity of symptoms based on case definitions of IBS were abstracted from the medical records. RESULTS: During the study period, 890 incident cases of IBS were identified. Only 404 met one or more of the three diagnostic criteria, 340 (84%) met only the Manning criteria, 35 (10%) met only Manning and Rome I criteria, 4 (1%) met both Manning and Rome II criteria, and 25 (6%) met Manning and Rome I and Rome II criteria. Age adjusted incidence rates per 100,000 person-years for validated IBS cases during the observational period were 87 to 170 by Manning (lower confidence interval [CI]: 57-127, upper CI: 116-213), 8 to 34 (lower CI: 0-14, upper CI: 16-53) for Rome I and 3 to 16 (lower CI: 0-3, upper CI: 8-28) for Rome II. Comparison of Rome I and Rome II showed moderate concordance (kappa statistic = 0.51; 95% CI: 0.39-0.64). CONCLUSIONS: Only a small percentage of IBS cases with assigned diagnostic codes met case definition criteria for IBS. There were low concordance rates among the three diagnostic criteria applied.

A pathologic re-review of follicular thyroid neoplasms: the impact of changing the threshold for the diagnosis of the follicular variant of papillary thyroid carcinoma.

BACKGROUND: Histopathologic criterion for follicular variant of papillary thyroid cancer (FVPTC) has only recently been utilized universally. The purpose was to determine whether, on review, these criteria would result in a change in diagnosis of follicular neoplasm (FN). METHODS: A ten-year clinical cohort included patients with a diagnosis of a follicular adenoma, follicular carcinoma (FC), or FVPTC. The archived sections were re-examined by two pathologists blinded to the original diagnoses. Clinical follow-up, including ultrasonography, was carried out on all patients with a change in diagnosis. RESULTS: One hundred eighty-five patients met the inclusion criteria. Initially, 118 were benign, 56 were FVPTC, and 11 were FC. Overall, 46 (25%) patients had a change in diagnosis on re-review; 35 were reclassified from a benign diagnosis to a re-reviewed malignant diagnosis, with 5 reclassified as minimally invasive FC, 4 as occult PTC, and 26 (74%) as FVPTC. Of the 26 FVPTC, only 10 (38%) had undergone a total thyroidectomy (TT). The mean follow-up was 105 months (range, 24-156). None of these patients had evidence of recurrent or persistent disease. Eleven patients were reclassified to a benign diagnosis. Eight have undergone a TT, with 3 of these patients receiving I(131) ablation therapy. A third independent thyroid pathologist also reviewed the histopathologic slides of these 46 patients and concurred with the change in diagnosis in 41 of the 46 patients. CONCLUSIONS: Reclassification of FN increased malignant lesions from 36% to 48%. Although there have been no clinical ramifications in the patients with a changed diagnosis, the ethical issues surrounding these 46 patients are important and present a substantive quandary to the clinicians responsible for their care.

Frequency and outcome of cervical cancer prevention failures in the United States.

We measured the frequency and outcome of cervical cancer prevention failures that occurred in the Papanicolaou (Pap) and colposcopy testing phases involving 1,646,580 Pap tests in 4 American hospital systems between January 1, 1998, and December 31, 2004. We defined a screening failure as a 2-step or greater discordant Pap test result and follow-up biopsy diagnosis. A total of 5,278 failures were detected (0.321% of all Pap tests); 48% and 52% of failures occurred in the Pap test and colposcopy phases, respectively. Missed squamous cancers (1 in 187,786 Pap tests), glandular cancers (1 in 19,426 Pap tests), and high-grade lesions (1 in 6,870 Pap tests) constituted 4.1% of all failures. Unnecessary repeated tests or diagnostic delays occurred in 70.8% and 63.9% of failures involving high- and low-grade lesions, respectively. We conclude that cervical cancer prevention practices are remarkably successful in preventing squamous cancers, although a high frequency of failures results in low-impact negative outcomes.

Multivariate probability-based detection of drug-induced hepatic signals.

Clinical signal detection of drug-induced hepatic effects is a very inexact science. Ordinary clinical laboratory tests are the primary biomarkers for liver changes. Heuristic rules have been developed by clinicians for diagnosing liver disease and monitoring these changes. These are based on laboratory reference limits, which are also largely heuristic. This article reviews some of the statistical characteristics of univariate reference limits and shows how they can and should be extended to multivariate reference regions. For instance, in the univariate approach, the probability of a false positive cannot be specified and grows with increasing numbers of analytes evaluated. However, accurate reference regions require very large samples from reference populations. Although the uniformly minimum variance unbiased estimator can greatly improve the mean-squared-error efficiency relative to a maximum likelihood estimator, it still requires tens of thousands of reference samples to estimate the 95% reference region for 20 analytes to an order of 95 +/- 1%, for example. Methods for constructing the elliptical reference region estimators and for sample size determination are provided. It is not feasible for small laboratories to make these calculations unless more rigorous methods of standardisation can be imposed and data merged across institutions. Large healthcare systems with electronic medical records and large pharmaceutical companies singly or in collaboration could generate sufficient sample sizes for accurate reference regions if techniques to make inter-laboratory results comparable are implemented. Exiting a reference region, whether population-based or individualised, can only tell you when the patient has changed from steady state. The region into which the patient's results enter and dynamics of this change are likely to contain considerable biological information. An example of this is Hy's rule. As the number of new, expensive biomarkers grows, it may be more cost-effective to find better ways to use the data we already collect, using the new biomarkers for validation. Mathematics and computers can help do this.

Do we know what people die of in the emergency department?

OBJECTIVE: To establish the discrepancy rate between the predicted cause of death and the actual cause of death as determined by postmortem examination result, for all deaths in the emergency department reported to the Scottish Procurator Fiscal and subsequently undergoing postmortem examination. METHODS: A prospective study of all patients who were dead on arrival or died in the emergency department of a busy Glasgow hospital over a 12 month period. The most senior emergency physician present at the time of death predicted the cause of death. This was then compared to the actual postmortem examination determined cause of death and was considered either to be correct or incorrect. RESULTS: During the study period, 146 patients were pronounced dead in the department. Of these, 81 patients (age range 39-99 years, median 71; male:female 2.5:1) had death certificates issued, 63 patients (age range 26 days to 99 years, median 48; male:female 2.4:1) had a postmortem performed by the forensic pathologist, and two patients underwent a "view and grant". Of the 63 deaths reported to the Procurator Fiscal, the emergency physician attributed 51 (80.1%) to non-trauma, 9 (14.2%) to trauma, and in 3 (4.7%) cases were uncertain. Of the 63 (39.7%) deaths, 25 were inaccurately predicted (99% confidence interval 24.3% to 56.6%; p<0.0)1. Cardiovascular related and drugs poisoning deaths occurred most commonly. They were also the most accurately predicted cause of deaths. Intracranial events, pulmonary thromboembolism, and airway obstruction were also frequently predicted, but were often wrong. CONCLUSIONS: This study highlights the difficulties in accurately identifying cause of death for patients who die suddenly. This could have implications for the accuracy of health service statistics.

Inter-rater agreement in judging errors in diagnostic reasoning.

CONTEXT AND OBJECTIVE: Inter-rater agreement is essential in rating clinical performance of doctors and other health professionals. The purpose of this study was to establish inter-rater agreement in categorising errors in the diagnostic process made by clinicians using computerised decision support systems. METHODS: Eight possible error categories were developed for coding errors in diagnostic hypotheses and plans for next steps in the work-up. Two independent doctor judges rated 54 work-ups (representing 2 cases, each worked-up by 27 doctors). Inter-rater agreement between the 2 raters was computed using the kappa coefficient. RESULTS: High inter-rater agreement was achieved in all categories except where the manual was not sufficiently specific and raters had to use their judgement. As is typical of the kappa coefficient, however, agreement corrected for chance fell markedly into the "poor" range when the percentages of expected and observed agreement were about the same. CONCLUSION: Raters can achieve good agreement in categorising errors provided they are given explicit scoring rules and do not rely solely upon clinical judgement. The kappa coefficient has limitations in cases where the expected agreement between judges is high and variability is low. The use of 2 indices to assess agreement, analogous to test sensitivity and specificity, is recommended.

Missed acute cardiac ischemia in the ED: limitations of diagnostic testing.

Correctly identifying and appropriately triaging patients who present to the ED with the broad range of symptoms suggestive of acute cardiac ischemia (ACI: unstable angina pectoris [UAP] and acute myocardial infarction [AMI]) remains one of the greatest challenges in EM. Although a number of diagnostic technologies have been described to aid in this triage process, each of these tests or technologies has limitations. We report a case series in which either the use of adjuncts with unknown performance or tests with known but not considered limitations could have contributed to the failure to appropriately triage and treat patients with ACI. Each case illustrates different aspects of this clinical challenge. One case illustrates the hazards of reliance on a single set of negative cardiac biomarkers. The limitations of a negative exercise electrocardiographic stress test (ETT) are illustrated in the second case. Finally, the limitations of a negative coronary angiogram, the "gold standard" test for symptomatic coronary artery disease, are discussed. We review the literature on technologies to aid in the evaluation of patients who present to the ED with symptoms suggestive of ACI.

[The incorrect laboratory result. Part 1: Pre- and postanalytical phase]. / Der "fehlerhafte" Laborbefund Teil 1: Fehlerquellen der prä- und postanalytischen Phase.

Laboratory results play a key role in the diagnostic procedure, the decision of treatment and the follow up of diseases. A high validity of the laboratory result is an important precondition for the efficacy in clinical medicine. Analytical standards have been developed under strong quality control criteria, however, there are no sufficiently defined standards for the pre- and postanalytical phase in laboratory diagnostics. Thus, most of laboratory errors are caused by pre- and postanalytical mistakes. The competent knowledge of possible sources for laboratory errors is a critical precondition for their avoidance. Diagnostic sensitivity and specificity play an important role for the choice of a laboratory test, whereas the predictive value should be considered for the medical relevance of the test result. In addition, many interference factors, which may influence the results of the laboratory tests have to be considered as age, sex, race, lifestyle, drugs, pregnancy, specimen collection, quality and handling as well as special factors, which may influence the complex of immunological and molecular diagnostics.