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.

[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.

[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.

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.

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.

Enhanced clinical consulting--moving toward the core competencies of laboratory professionals.

The large menu of laboratory assays available today makes it increasingly difficult for the non-specialist to order all necessary tests, avoid medical errors, and still contain cost. Curbside consultations, "intelligent" laboratory information systems, and medical information from the Internet cannot fully fill the need for expert advice on test selection and interpretation of laboratory results. In this communication, we show the need for a more active role for laboratory physicians to select and interpret tests, demonstrate that existing attempts to deal with this issue are insufficient, and describe the model system which we have instituted at our institution. We combine reflexive testing algorithms with narrative interpretations provided by medical laboratory professionals and thereby enable physicians to obtain relevant laboratory results and to arrive at a definitive diagnosis without having to order individual tests. In our experience, such an arrangement can significantly improve the quality of care and reduce the cost per case by decreasing the time to diagnosis, the number of tests ordered, and the number of patient visits. In addition, interpretations provide a new source of professional revenue for the expert laboratory physician. This leads to a new role for laboratory professionals, in which their expertise in the selection and interpretation of laboratory tests is fully utilized.

Rules-based detection of discrepancies between TSH and free T4 results.

BACKGROUND: Analytical errors in clinical laboratory testing are unavoidable. Recent reports have suggested the idea of "physiological profiling" which uses several results from a given patient to identify clinically unlikely results. The objective of this study was to establish rules-based criteria for identifying physiologically unlikely TSH and free T(4) (fT(4)) results. METHODS: For a 30-month period, all samples with fT(4) concentrations >2 ng/dl and TSH concentrations >0.1 micro IU/ml were investigated. RESULTS: Among 7918 plasma samples for which both TSH and fT(4) concentrations were measured, 18 (0.23%) had fT(4) and TSH exceeding the investigated limits. Of these, two were due to heterophile antibody interference (with the TSH assay), one was proven to be due to random error, four could be explained by the patients' conditions, three were from infants <1 week of age, and the remaining eight were unresolved, primarily due to insufficient sample, discarded samples, and inability to obtain patient histories. CONCLUSIONS: This study defined a rules-based alert system for clinically unlikely combinations of TSH and fT(4) results. This pilot study demonstrates that this system is capable of detecting at least two different types of laboratory errors that would have otherwise gone undetected.

What is the rational diagnostic approach to spinal disorders?

A problem that is encountered in patients with low back pain is that a definite diagnosis is rare. The heart of our clinical dilemma is how best to diagnose those rare patients with severe disease as early as possible. The main reasons for diagnostic errors have been summarized in this chapter. Numerous guidelines have been developed to help in the approach to this difficult problem. However, the limitations of such an approach are highlighted. History and clinical examination are the best single test for diagnostic purposes and neither questionnaires nor computers can replace the clinician. However, the values of clinical abilities should not be overestimated. Finally, the clinical application of guidelines needs to be re-evaluated for each individual patient.

Correcting out-of-plane errors in two-dimensional imaging using nonimage-related information.

Two-dimensional imaging with a single camera assumes that the motion occurs in a calibrated plane perpendicular to the camera axis. It is well known that kinematic errors result if the object fails to remain in this plane and that if both the distance to the calibration plane from the camera and the distance out-of-plane are known, an analytical correction for the out-of-plane error can be made. Less well appreciated is that out-of-plane distance can frequently be acquired from other, nonimage-related information. In the two examples given, the mediolateral center of pressure coordinate of the foot measured from a force plate and the measured landing point of a shot put throw were used. In both cases, the resulting out-of-plane correction improved the accuracy of the 2-D kinematic data dramatically. These examples also demonstrate that the use of nonimage-related data can increase the accuracy of kinematic data without an increase in the complexity of the experiment.

Selective or universal diagnostic testing for gestational diabetes mellitus.

OBJECTIVES: To estimate the effect of selective diagnostic testing for gestational diabetes mellitus (GDM): (1) based on evaluation of risk factors; and (2) based on the recommendations of The Fourth Workshop-Conference on GDM. METHODS: A retrospective study was performed of 147 pregnancies complicated by GDM delivered in Kaunas University of Medicine Hospital. The maternal and fetal outcomes and the main risk factors were compared with the same data of a randomly selected 300 women with normal glucose tolerance testing. Logistic regression was used to estimate the odds ratios with 95% confidence interval (CI). RESULTS: The prevalence of all risk factors was significantly higher in the group with GDM, but 29 of these women (23.13%) had no risk factors. Sixteen women (10.9%) with GDM were at low risk and would remain undiagnosed if selective screening would be used. CONCLUSIONS: The recommendations not to test low-risk group women are doubtful and require further examination whereas universal screening of all pregnant women would be justified.

Fine-needle aspiration of the thyroid: rate and causes of cytohistopathologic discordance.

Fine-needle aspiration (FNA) of the thyroid gland is a widely utilized, sensitive, specific, and cost-effective method for the evaluation of thyroid nodules. The purpose of this study was to evaluate the accuracy of thyroid FNA and causes of cytohistological discordance in our institution. Six hundred twenty-five thyroid FNAs obtained from 503 females (mean age, 54) and 122 males (mean age, 51) in whom histopathologic follow-up material was available for review, were analyzed. FNAs were classified as: nondiagnostic, negative, intermediate, and positive for malignancy, and the histopathologic material was categorized as benign or malignant. The review revealed 93% sensitivity and 96% specificity for the FNA diagnoses. The FNA results were diagnostic in 87%, indeterminate in 6%, and nondiagnostic in 7% of the cases. Cytohistologic correlation was achieved in 88% of the cases. The false-negative rate was 4% and the false-positive rate was 8%. The most common pitfalls for false-negative diagnoses consisted of suboptimal material and underdiagnosis of papillary carcinoma due to cystic degeneration. The most common pitfall for false-positive cases was overdiagnosis of follicular neoplasms. Our study confirmed that FNA of thyroid nodules can be performed with high sensitivity and specificity by experienced clinicians or pathologists. The application of strict specimen adequacy rules for FNA interpretation is likely to decrease the rate of false-negative and false-positive diagnoses.

Point-of-care testing and recognizing and preventing errors.

Jenny, the practice nurse of a busy GP surgery, was asked to carry out a commercially available test to exclude a diagnosis of infectious mononucleosis. The test was negative. The patient was prescribed amoxycillin and later developed a severe rash. However, the blood tests from the local pathology laboratory showed that the patient did have infectious mononucleosis. The GP discovered from colleagues that over the last few weeks other patients as the surgery had been recorded as having negative tests but positive laboratory results had later followed.