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This paper investigates estimating and testing treatment effects in randomized control trials where imperfect diagnostic device is used to assign subjects to treatment and control group(s). The paper focuses on pre-post design and proposes two new methods for estimating and testing treatment effects. Furthermore, methods for computing sample sizes for such design accounting for misclassification of the subjects are devised. The methods are compared with each other and with a traditional method that ignores the imperfection of the diagnostic device. In particular, the likelihood-based approach shows a significant advantage in terms of power, coverage probability and, consequently, in reduction of the required sample size. The application of the results are illustrated with data from an aging trial for dementia and data from electroencephalogram (EEG) recordings of alcoholic and non-alcoholic subjects. Copyright © 2016 John Wiley & Sons, Ltd.

Introduction Rapid on-site evaluation (ROSE) has been widely used to improve diagnostic adequacy and facilitate specimen triage. Telecytology ROSE has gained popularity recently and shown high concordance with traditional ROSE. However, telecytology involves multiple personnel and technical devices that could introduce additional errors. The aim of this paper is to share errors encountered and lessons learned since employing telecytology for ROSE at our institution. Methods The laboratory information system was searched for all documented telecytology ROSE errors from 2017 to 2019. These errors were subclassified as technical errors, cytotechnologist-related errors and pathologist-related errors. The following details were recorded for each reported event: type of error, reason for error, ROSE diagnosis, final diagnosis and actions taken to avoid future errors. Results Telecytology ROSE errors were documented in 46 (1.3%) sessions. Ten (22%) had technical errors, 13 (28%) were owing to cytotechnologist errors and 23 (50%) were attributed to pathologist interpretation errors. The majority of the technical (90%) and cytotechnologist errors (85%) occurred within the first year of implementation of telecytology. Common ROSE misinterpretation errors included missing microorganisms, misclassifying neuroendocrine tumours as other neoplasms and overcalling malignancy on gastrointestinal endoscopic procedures. Conclusions A variety of errors may occur during telecytology ROSE. While some errors are inevitable (eg, information technology downtime), certain telecytology errors can be reduced by increasing staff familiarity with the system, providing timely feedbacks and taking prompt corrective actions. We recommend establishing a mechanism to document and act upon recorded errors as part of a telecytology quality improvement programme.

Some research suggests that 40% of people in the vegetative state are misdiagnosed. This review investigates the frequency, nature and causes of reported misdiagnosis of patients in the vegetative state, focusing on the nature of the error. It is a systematic review of all relevant literature, using references from key papers identified. The data are summarized in tables. Five clinical studies of the rate of misdiagnosis in practice were identified, encompassing 236 patients in the vegetative state of whom 80 (34%) were reclassified as having some awareness, often minimal. The studies often included patients in the recovery phase after acute injury, and were poorly reported. Five systematic reviews of signs and technologically based neurophysiological tests were identified, and they showed that most studies were small, lacked accurate or important details, and were subject to bias. Studies were not replicated. Many signs and tests did not differ between people in the vegetative state and in the minimally conscious state, and those that did were unable to diagnose an individual patient. The few single case reports suggest that failure to ensure an accurate diagnosis of the underlying neurological damage and dysfunction could, rarely, lead to significant misdiagnosis usually in patients who had brain-stem damage with little thalamic or cortical damage. Significant misdiagnosis of awareness, with an apparently 'vegetative' patient having good awareness, is rare. Careful neurological assessment of the cause and routine measurement of awareness using the Coma Recovery Scale - Revised should further reduce mistakes.

In epidemiological studies of secondary data sources, lack of accurate disease classifications often requires investigators to rely on diagnostic codes generated by physicians or hospital systems to identify case and control groups, resulting in a less-than-perfect assessment of the disease under investigation. Moreover, because of differences in coding practices by physicians, it is hard to determine the factors that affect the chance of an incorrectly assigned disease status. What results is a dilemma where assumptions of non-differential misclassification are questionable but, at the same time, necessary to proceed with statistical analyses. This paper develops an approach to adjust exposure-disease association estimates for disease misclassification, without the need of simplifying non-differentiality assumptions, or prior information about a complicated classification mechanism. We propose to leverage rich temporal information on disease-specific healthcare utilization to estimate each participant's probability of being a true case and to use these estimates as weights in a Bayesian analysis of matched case-control data. The approach is applied to data from a recent observational study into the early symptoms of multiple sclerosis (MS), where MS cases were identified from Canadian health administrative databases and matched to population controls that are assumed to be correctly classified. A comparison of our results with those from non-differentially adjusted analyses reveals conflicting inferences and highlights that ill-suited assumptions of non-differential misclassification can exacerbate biases in association estimates.

Two common problems in assessing the accuracy of traditional Chinese medicine (TCM) doctors in detecting a particular symptom are the unknown true symptom status and the ordinal-scale of the symptom status. Wang et al. (Biostatistics 2011; DOI: 10.1093/biostatistics/kxq075) proposed a nonparametric maximum likelihood method for estimating the accuracy of different TCM doctors without a gold standard when the true symptom status is measured on an ordinal-scale. A key assumption of their work is that the diagnosis results are independent conditional on the gold standard. This assumption can be violated in many practical situations.In this paper, we propose a random effects modeling approach that extends their method to incorporate dependence structure among different tests or doctors. The proposed method is illustrated on a real data set from TCM, which contains the diagnostic results from five doctors for the same patients regarding symptoms related to Chills disease. The same data set was analyzed by Wang et al. under the conditional independence assumption. In addition, we also discuss an ad hoc test for the model fitting and a likelihood ratio test on the random effects.

Sensitivity, specificity, positive and negative predictive value are typically used to quantify the accuracy of a binary screening test. In some studies, it may not be ethical or feasible to obtain definitive disease ascertainment for all subjects using a gold standard test. When a gold standard test cannot be used, an imperfect reference test that is less than 100 per cent sensitive and specific may be used instead. In breast cancer screening, for example, follow-up for cancer diagnosis is used as an imperfect reference test for women where it is not possible to obtain gold standard results. This incomplete ascertainment of true disease, or differential disease verification, can result in biased estimates of accuracy. In this paper, we derive the apparent accuracy values for studies subject to differential verification. We determine how the bias is affected by the accuracy of the imperfect reference test, the percent who receive the imperfect reference standard test not receiving the gold standard, the prevalence of the disease, and the correlation between the results for the screening test and the imperfect reference test. It is shown that designs with differential disease verification can yield biased estimates of accuracy. Estimates of sensitivity in cancer screening trials may be substantially biased. However, careful design decisions, including selection of the imperfect reference test, can help to minimize bias. A hypothetical breast cancer screening study is used to illustrate the problem.

The area (A) under the receiver operating characteristic curve is commonly used to quantify the ability of a biomarker to correctly classify individuals into two populations. However, many markers are subject to measurement error, which must be accounted for to prevent understating their effectiveness. In this paper, we develop a new confidence interval procedure for A which is adjusted for measurement error using either external or internal replicated measurements. Based on the observation that A is a function of normal means and variances, we develop the procedure by recovering variance estimates needed from confidence limits for normal means and variances. Simulation results show that the procedure performs better than the previous ones based on the delta-method in terms of coverage percentage, balance of tail errors and interval width. Two examples are presented.

Title. Alarm limit settings for early warning systems to identify at-risk patients. Aim. This paper is a report of a study conducted to provide objective data to assist with setting alarm limits for early warning systems. Background. Early warning systems are used to provide timely detection of patient deterioration outside of critical care areas, but with little data from the general ward population to guide alarm limit settings. Monitoring systems used in critical care areas are known for excellent sensitivity in detecting signs of deterioration, but give high false positive alarm rates, which are managed with nurses caring for two or fewer patients. On general wards, nurses caring for four or more patients will be unable to manage a high number of false alarms. Physiological data from a general ward population would help to guide alarm limit settings. Methods. A dataset of continuous heart rate and respiratory rate data from a general ward population, previously collected from July 2003–January 2006, was analyzed for adult patients with no severe adverse events. Dataset modeling was constructed to analyze alarm frequency at varying heart rate and respiratory rate alarm limits. Results. A total of 317 patients satisfied the inclusion criteria, with 780·71 days of total monitoring. Sample alarm settings appeared to optimize false positive alarm rates for the following settings: heart rate high 130–135, low 40–45; respiratory rate high 30–35, low 7–8. Rates for each selected limit can be added to calculate the total alarm frequency, which can be used to judge the impact on nurse workflow. Conclusion. Alarm frequency data will assist with evidence-based configuration of alarm limits for early warning systems.

Electric pulp testing (EPT) has been available for more than a century and used in dental practices worldwide. This article provides an overview of this diagnostic aid. The PubMed database from 1953 was used initially; the reference list for pulp testing featured 1071 articles, and for EPT identified 121 papers. A forward search was undertaken on these articles and using selected author names. Potentially relevant material was also sought in contemporary endodontic texts, while older textbooks on endodontics, operative dentistry and pain revealed historic information and primary research not found electronically. A short account of the innervation of the pulp is followed by an historic overview. Clinical considerations discussed include tooth isolation, glove wearing and tester electrode placement. Orthodontic treatment, pacemaker wearing and patient medications are considered. Research applications are also discussed. While EPT is valuable, no single pulp testing technique can reliably diagnose all pulp conditions. Careful collection of patient history regarding the problem tooth and prudent use of appropriate radiographs are also helpful. The shortcomings of electric tests, especially in the case of immature and concussed teeth, must be understood. The demeanour of the patient and the responses given by control teeth also require careful consideration.

The dermatoglyphic discriminants proposed by Penrose & Loesch were used for differentiation between samples of 183 patients with Down's syndrome and 125 controls. The discriminant weightings determined for our Dutch individuals did not deviate much from those determined by Penrose & Loesch for individuals in Great Britain. The estimated percentage of misclassification compares well with the same quantity calculated in the original papers. Moreover, since the method compares well with other known scoring methods, it can be used to advantage in cases of unknown or discrepant symptoms in a patient. The disadvantage of the method, for the confirmation of a clinical diagnosis of Down's syndrome, seems to be that it is rather laborious.

Although there is some debate about the relative prevalence rates of depression in African Americans compared to Whites, there is little debate among investigators that there is a shortage of research data on depression in African Americans generally, and more specifically on African American women. Lack of adequate and sufficient research on African Americans contributes to the problems of misdiagnoses, under-diagnoses, and undertreatment of depression in African Americans, generally, and more specifically, African American women, the focus of this special section. African American women are understudied, underserved, and misdiagnosed as a group. A paucity of studies on depression in African American women has existed for decades. This special series of papers will highlight the existing problem of depression in African American women with a focus on diagnostic, treatment, and research issues.

We have previously shown that upon receipt of inadequate cervical smear test results, women have elevated levels of state anxiety and concern about their test results, similar to those of women receiving abnormal smear test results. The current paper reports data on the psychological impact three months after receiving an inadequate smear test result. Two groups of women who initially received a normal test result (n=184) or either a first or non-consecutive inadequate smear test result (n=140) responded. Women with initially received inadequate smear test results no longer had higher state anxiety than women who received normal test results. However, women who initially received inadequate smear test results were still more concerned about their test results and less satisfied with the information they had received about these initial test results, even after receiving normal results from repeat cervical smear tests. Concern was strongly predicted by dissatisfaction with information provided about inadequate smear test results. These results underscore the need to improve communication about inadequate cervical smear test results.

The diagnosis of developmental dyslexia (DD) is reliant on a discrepancy between intellectual functioning and reading achievement. Discrepancy-based formulae have frequently been employed to establish the significance of the difference between 'intelligence' and 'actual' reading achievement. These formulae, however, often fail to take into consideration test reliability and the error associated with a single test score. This paper provides an illustration of the potential effects that test reliability and measurement error can have on the diagnosis of dyslexia, with particular reference to discrepancy models. The roles of reliability and standard error of measurement (SEM) in classic test theory are also briefly reviewed. This is followed by illustrations of how SEM and test reliability can aid with the interpretation of a simple discrepancy-based formula of DD. It is proposed that a lack of consideration of test theory in the use of discrepancy-based models of DD can lead to misdiagnosis (both false positives and false negatives). Further, misdiagnosis in research samples affects reproducibility and generalizability of findings. This in turn, may explain current inconsistencies in research on the perceptual, sensory, and motor correlates of dyslexia.

The diagnosis of pulmonary embolism (PE) is difficult with many patients treated without the disease or left untreated without an adequate diagnostic work up. Recent advances in PE diagnosis are reviewed. The use of risk stratification in PE diagnosis is strongly recommended and evidence on how it can best be performed summarized. The Ginsberg/Wells stratification rule is recommended currently as the best validated rule. Computed tomographic pulmonary angiography (CTPA) was found to have quite poor sensitivity and to be poorly validated. It is recommended as adequate as a positive test in moderate/high risk groups and an exclusionary test in low risk groups or where an adequate alternative diagnosis is found. For D-Dimer tests the only test with adequate sensitivity and validation in management studies is the VIDASCopyright D-Dimer. This is in low/intermediate risk groups in the ED population. The Simpli-RedCopyright test is also reviewed but is too insensitive for most populations. Echocardiography: this is good in compromised patients as it is a bedside test which when negative virtually excludes PE. If positive in the right setting it has a high positive predictive value. A negative echocardiogram predicts a benign clinical course for PE. The rest of the paper details the authors approach to integrating these new techniques with established algorithms and where progress is likely to occur in the next few years. These include improvements in CTPA (plus the addition of CT venography), new point of care D-Dimer tests, better risk stratification rules and integration of new strategies with artificial neural networks or computerized guidelines.

Accurately evaluating the size of a neurovascular lesion is essential for properly devising treatment strategies. The magnification factor must be considered in order to measure the dimension of a lesion from an angiogram. Although a method to calculate the magnification of the lesion by linear interpolation of the measurable magnification factors of two markers has been in use, this paper shows that it can be inaccurate. By deriving the exact formula for calculating the magnification factor at the level of the lesion, the error generated by the linear interpolation of magnification factor has been evaluated. This error was found to depend on source‐to‐skin distance (SSD), the location of the lesion in the head, and the head size. The closer the head is to the focal spot and the nearer the lesion is to the center of the head, the larger is the error. Since clinicians tend to use high geometric magnification (i.e., small SSD) in interventional procedures, there exists a possible consequential error of more than 3% in lesion sizing if the linear‐interpolation calculation method is used. It is thus recommended that the exact formula derived here be used to calculate the magnification factor to improve accuracy. PACS number(s): 87.57.–s, 87.57.Nk, 87.59.Dj

Purpose To compare levels of recorded risk factors and drug treatment between patients with validated and non-validated diagnoses of coronary heart disease (CHD) in Northern Ireland. Methods Patients with a nitrate prescription in the previous year or a CHD Read code were identified from computer records of 25 practices, stratified by partnership size and area board. Computer and paper records of a random sample of 10% of these were searched for specified criteria to validate the diagnosis of CHD. The diagnosis was considered valid if the patient was found to have one or more positive investigations for CHD. Records of blood pressure, cholesterol, blood sugar, body mass index and drugs prescribed were taken into account. Results The combined practice population was 151 071; 7338 (4.86%) were identified by the computer search as meeting the defined entry criteria for CHD. Among the 10% random sample the diagnosis of CHD could not be validated for 36.5% (265/727). Significantly more patients with a validated than non-validated diagnosis had recorded cholesterol levels below 5.0 mmol/l (55.8 vs. 34.5%, p

In evaluating the accuracy of diagnostic tests there are many situations where the true disease status can be one of multiple disorders. For example, when paediatric patients suffer acute abdominal pain, the underlying diagnosis could be appendicitis, intestinal obstruction, gastroenteritis, urinary tract infection, etc. In this paper we describe a format for collecting data for the case of multiple truth states. This new format allows one to make pairwise comparisons of the diagnostic accuracy between all of the different truth states. We propose a summary measure of accuracy which is a weighted average of the pairwise estimates of accuracy. Estimators are derived for the variance and covariance of the estimated summary accuracy. The small sample properties of the estimators are evaluated in a Monte Carlo simulation study. The new data collection format and summary measure were used in a paediatric acute abdominal pain study; data from this study are used to illustrate the methods.

Refractive error measurements made with the Badal optometer typically register more myopia than is actually present. In this paper we measured the influence of the image size on the endpoint of a Badal optometer's refractive error measurement. The optometer was modified with a camera's zoom lens in such a way that the retinal image size could be controlled. It was found that retinal image size is a major factor in controlling the subjective endpoint. When retinal image size is diminished rather than increased as the target approaches the subject, as is the case under normal circumstances, the perceived endpoint more closely agrees with the actual refractive error.

Of the 16 cases of fine-needle aspiration biopsy (FNAB) of pilomatrixomas reported since 1982, only 25% were correctly diagnosed prior to excision. The most common pitfall encountered was a false-positive or suspicious diagnosis of a carcinoma. All the reported cases had a polymorphous cellular and noncellular composition on low-power examination, including numerous basaloid cells, ghost cells, squamoid cells, foreign body giant cells, mixed inflammatory cells, keratin clumps, and granular debris which might be easily mistaken for a malignant necrotic background. Amongst these, ghost cells were the critical pathognomonic feature. This paper reported a further finding that had been underemphasized in the literature: masses of refractile orangeophilic keratin clumps representing compact sheets and stacks of ghost cells. Their presence should alert the observer to search for the more diagnostic dispersed forms which otherwise might be inconspicuous and easily overlooked.

Please cite this paper as: van Jaarsveld C, Llewellyn C, Fildes A, Fisher A, Wardle J. Are my twins identical: parents may be misinformed by prenatal scan observations. BJOG 2012;119:517–518.

The effect of abnormal cell proportion on the performance of an automated cervical prescreening system is discussed in K.R. Castleman and B.S. White, Cytometry 2:155-18. The model employed assumes fixed proportions of abnormal cells, both in the design stage and in the test stage. In the present paper, an extended model is developed that allows for random variability of this proportion. It is shown, that there is a fundamental, non-zero lower limit to the false-negative specimen error rate, which depends only on the coefficient of variation. This limit may be reached even for moderate values of the coefficient of variation, which implies that a satisfactory prescreening system may not be feasible.

This paper details our initial experiences with a semi-automated leucocyte adherence inhibition (SALAI) assay in patients with colorectal disease. Two assay systems were used. Leucocytes from blood donors and patients with different colorectal diagnoses were tested for sensitization to colorectal tumour extracts, and leucocytes from healthy blood donors were assayed with serum from blood donors or patients to determine whether the serum itself contained factors which would react with the non-sensitized leucocytes in the test system. The sensitivity of the SALAI assay using patients' leucocytes was 64%, and the specificity was 68%. Discriminant analysis did not affect the sensitivity of the assay for colorectal cancer (64%), although the specificity was increased for all patients except those with malignant disease other than colorectal cancer. The sensitivity of the SALAI assay using patients' serum was 50% but the specificity was 74%. Discriminant analysis increased the sensitivity of this assay to 80% but specificity was reduced to 61%. Thus, the SALAI assay with patients' serum, although potentially more advantageous than the assay using patients' leucocytes in the clinical setting, was less specific. Furthermore, samples from patients with early colorectal cancers were less reactive making the serum assay unsuitable for screening asymptomatic patients. The SALAI assay using patients' leucocytes, however, has a higher sensitivity than most reported variations of the assay but a slightly lower specificity. It is suggested that the SALAI assay is preferable to other methods for leucocyte adherence inhibition (LAI) testing.

This paper describes an 18-year-old patient with Rokitansky-Küster-Hauser (R-K-H) syndrome. In this case, apart from the usual alterations associated with the R-K-H syndrome, such as aplasia of the Müllerian ducts, renal agenesis, ectopic kidney and anomalies of vertebral column, ribs and hips, rare skeletal, unilateral abnormalities of the left hand and foot were present, such as ectrodactyly. This malformation, seen in prepubertal age, had led to an incorrect diagnosis of acrorenal syndrome.