A methodological framework to distinguish spectrum effects from spectrum biases and to assess diagnostic and screening test accuracy for patient populations: Application to the Papanicolaou cervical cancer smear test

<p>Abstract</p> <p>Background</p> <p>A spectrum effect was defined as differences in the sensitivity or specificity of a diagnostic test according to the patient's characteristics or disease features. A spectrum effect can lead to a spectrum bias when subgroup variations in sensitivity or specificity also affect the likelihood ratios and thus post-test probabilities. We propose and illustrate a methodological framework to distinguish spectrum effects from spectrum biases.</p> <p>Methods</p> <p>Data were collected for 1781 women having had a cervical smear test and colposcopy followed by biopsy if abnormalities were detected (the reference standard). Logistic models were constructed to evaluate both the sensitivity and specificity, and the likelihood ratios, of the test and to identify factors independently affecting the test's characteristics.</p> <p>Results</p> <p>For both tests, human papillomavirus test, study setting and age affected sensitivity or specificity of the smear test (spectrum effect), but only human papillomavirus test and study setting modified the likelihood ratios (spectrum bias) for clinical reading, whereas only human papillomavirus test and age modified the likelihood ratios (spectrum bias) for "optimized" interpretation.</p> <p>Conclusion</p> <p>Fitting sensitivity, specificity and likelihood ratios simultaneously allows the identification of covariates that independently affect diagnostic or screening test results and distinguishes spectrum effect from spectrum bias. We recommend this approach for the development of new tests, and for reporting test accuracy for different patient populations.</p

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Management of thyroid cytological material, preanalytical procedures and bio-banking

Thyroid nodules are common and are increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. Fine needle aspiration cytology (FNAC) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goitre. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article discusses technical aspects (preanalytics) of performing thyroid FNAC, including image guidance and rapid on-site evaluation, sample collection methods (conventional slides, liquid-based methods, cell blocks) and storage (bio-banking). The spectrum of special studies (immunocytochemistry on direct slides or liquid-based cytology, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is also discussed

Management of thyroid cytological material, preanalytical procedures and bio-banking.

Thyroid nodules are common and are increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. Fine needle aspiration cytology (FNAC) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goitre. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article discusses technical aspects (preanalytics) of performing thyroid FNAC, including image guidance and rapid on-site evaluation, sample collection methods (conventional slides, liquid-based methods, cell blocks) and storage (bio-banking). The spectrum of special studies (immunocytochemistry on direct slides or liquid-based cytology, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is also discussed

Discriminating benign from malignant thyroid lesions using artificial intelligence and statistical selection of morphometric features

The objective of this study was to perform a comparative investigation of the capability of various classifiers in discriminating benign from malignant thyroid lesions. Using May Grunvald-Giemsa-stained smears taken by fine needle aspiration (FNA) and a custom image analysis system, 25 nuclear features describing the size, shape and texture of the nuclei were measured in each case. A statistical pre-processing of features revealed that only 4 of the 25 features are important when discriminating benign from malignant thyroid lesions, which were transformed and fed to four classifiers for subsequent analysis. The cases were divided into one set used for the training of classifiers, a second set used as the test set, and the remaining cases with no clear classification formed an ambiguous test set. Classification was performed at the nuclear and patient level. The technique described in this study produced encouraging results and promises to be a helpful tool in the daily cytological laboratory routine