How accurate are subjective judgements of a continuum?

AIMS: To assess the accuracy of subjective judgements of a uni-dimensional continuum. METHODS AND RESULTS: Twenty-four observers were asked to estimate the position of a dot placed between two lines using a 100-point scale. Each observer judged 20 different positions. Ninety-five percent of observations were between -7 and +9 of the true value. The median and the mean value of the estimates for each position were within one or two points of the true value in most cases with a maximum deviation of five. There was perfect correlation between the ranks of the median and the mean and the true value (correlation coefficient +1, P < 0.00001). The kappa values for interobserver agreement varied from 0.98 for two categories to 0.55 for 10 categories and 0.39 for 20 categories. Information transmitted increased from 0.98 bits with two categories to 2.83 bits with 20 categories. CONCLUSIONS: The experiment indicates that subjective judgements can be accurate but it is necessary to use a large number of categories. One hundred-point scales allow confidence intervals to be calculated and the intervals are reduced if the results from several observers are pooled. The mean and the median of the judgements of a large number of observers are close to objective reality and this approach could be used to define a gold standard of rankings of pathological continua such as cervical dyskaryosis or tumour differentiation. There is a reciprocal relationship between kappa values and information transmitted which demonstrates the fallacy of using kappa statistics in studies of continua.     

What are older peoples' experiences of taking antidepressants?

Background: Antidepressants are prescribed widely to older people but little is known about older peoples’ own reported experiences of taking them in routine practice. Methods: A doctor interviewed 92 people, aged over 65, with a hospital diagnosis of depression, who had been prescribed an antidepressant in the past year. Results: Most of the subjects were prescribed a selective serotonin reuptake inhibitor (SSRI), at a standard dose, for at least 8 weeks. Most people felt the antidepressants were helpful, although a third felt they made no difference. Two thirds of older people reported having adverse effects of which most were moderate or severe. The most common adverse effects were headache and dry mouth. Only a third said that they always took their tablets. Limitations: The sample was restricted to older people seen by hospital services. Interviews were carried out by a doctor and patients may not have been entirely truthful. Conclusions: Older people have important views about their treatment that they are prepared to tell a doctor. A lot of older people do not think their antidepressants are helpful, and the majority experience adverse effects. Many do not always take their medication. Doctors should routinely ask older people about their experiences of taking antidepressants.     

Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility?

AIMS: To assess inter/intraobserver variability in the interpretation of a series of digitised images of columnar cell lesions (CCLs) of the breast. METHODS: After a tutorial on breast CCL, 39 images were presented to seven staff pathologists, who were instructed to categorize the lesions as follows: 0, no columnar cell change (CCC) or ductal carcinoma in situ (DCIS); 1, CCC; 2, columnar cell hyperplasia; 3, CCC with architectural atypia; 4, CCC with cytological atypia; 5, DCIS. Concordance with the tutor's diagnosis and degree of agreement among pathologists for each image were determined. The same set of images was re-presented to the pathologists one week later, their diagnoses collated, and inter/intraobservor reproducibility and level of agreement for individual images analysed. RESULTS: Diagnostic reproducibility with the tutor ranged from moderate to substantial (kappa values, 0.439-0.697) in the first exercise. At repeat evaluation, intraobserver agreement was fair to perfect (kappa values, 0.271-0.832), whereas concordance with the tutor varied from fair to substantial (kappa values, 0.334-0.669). There was unanimous agreement on more images during the second exercise, mainly because of agreement on the diagnosis of DCIS. The lowest agreement was seen for CCC with cytological atypia. CONCLUSIONS: Interobserver and intraobserver agreement is good for DCIS, but more effort is needed to improve diagnostic consistency in the category of CCC with cytological atypia. Continued awareness and study of these lesions are necessary to enhance recognition and understanding.     

Risks of infection in xenotransplantation: what are they and how are they to be controlled?

Porcine grafts are a potential source of pathogenic agents capable of contaminating the recipient. The spread of porcine retroviruses in the patient's tissues is a major risk that must be rigorously evaluated. The control of the microbiological state of the pig donor, concerning retroviruses and other pathogens, is the necessary condition for controlling this risk.     

What are the standard functions of electronic clinical pathways?

Purpose

The present study was performed to determine the standard functions of electronic clinical pathways (eCP) embedded in electronic medical records with regard to demand definition.

Methods

The standard functions of eCP were decided by the required functions determined from interviews with hospital staff, those derived from the implementation of paper-based clinical pathways (CPs), and additional functions generated through the shift from a paper-based to an electronic system. Moreover, the proposed standard functions and those of eCP embedded in electronic medical records for large hospitals were compared by interviews with five vendors.

Results

Seventeen functions were deemed necessary for eCP, and these were classified into six categories: displaying, recording, ordering, editing, variance, and statistics. Although most of these functions are already included in eCP products, their implementations differ between products.

Conclusions

We propose 17 standard functions required for eCP embedded in electronic medical records. The functions for editing patient checklists, checking the occurrence of variance, and statistics are especially important and should be implemented as standard functions. This study will aid in the future development of eCP embedded in electronic medical records.     

Classification of pleomorphic sarcomas: where are we now?

Until a decade ago, so-called pleomorphic and storiform malignant fibrous histiocytoma (MFH) represented the most frequently diagnosed sarcoma, accounting for approximately 40% of adult mesenchymal malignancies. However, the latest World Health Organization classification of soft tissue tumours considers MFH a synonym for undifferentiated pleomorphic sarcoma. Historically, the term MFH was introduced in the medical literature in 1963 by Ozzello, O'Brien and Stout, on the basis of the acquisition of phagocytic properties observed in cultured fibroblasts. The existence of MFH as a well-defined clinicopathological entity became rapidly very popular and by the mid 1980s MFH represented the most common sarcoma in adults. With the advent of electron microscopy, immunohistochemistry and molecular genetics, it became clear that the so-called "facultative fibroblast" theory had no scientific grounds and, in 1992, a milestone paper eventually brought attention to the concept that MFH merely represented a morphological pattern shared by a wide variety of poorly differentiated malignant neoplasms, which include specific subtypes of pleomorphic sarcomas. Currently, accurate subclassification of pleomorphic sarcomas is mandatory as it enables recognition of non-sarcomatous lesions as well as pleomorphic neoplasms not associated with aggressive behaviour. Furthermore, as myogenic differentiation predicts aggressive clinical behaviour among pleomorphic sarcomas, precise histotyping allows prognostic stratification of patients.     

Inverted duplications: how many of them are mosaic?

The best-known situation indissolubly linked to mosaicism is the uniparental disomy where a trisomic or monosomic zygote develops at least one cell line with 46 chromosomes. The mosaicism normal/abnormal cell lines may remain confined to placenta or persist in the embryo. Here, we describe a second situation that might also be indissolubly linked to a mosaic condition or at least to a confined placental mosaicism. We analysed the case of a mosaicism del(8p)/inv dup(8p) found in prenatal diagnosis. We had already demonstrated that the first product of the abnormal meiotic recombination at the basis of the inv dup rearrangements is a dicentric chromosome. Its breakage leads to the formation of a deleted and an inv dup chromosome. Although we had previously assumed that the dicentric underwent a breakage at meiosis II so that the zygote inherited the inv dup chromosome, our findings and those of others indeed indicate that the dicentric may be inherited in the zygote and that it might persist as such in early postzygotic stages, then undergoing different breakages in different cells leading to different abnormal chromosomes, either deleted or duplicated. Selection versus the most viable cell line(s) results either in a confined placental mosaicism with the inv dup cell line as the only one present in the embryo or in children with both the deleted and the inv dup cell lines. Phenotype/karyotype relationships in inv dup rearrangements must also take into account the influence of the other abnormal cell line during embryogenesis.     

What are the best estimates of pediatric asthma control?

PURPOSE OF REVIEW: To evaluate asthma outcome measures in the face of the variable nature of asthma. The outcome measures are divided into objective and subjective clinical measures, humanistic measures such as quality of life, and costs of asthma control. RECENT FINDINGS: Objective measures of asthma include those traditionally used such as spirometry, peak expiratory flow rate, and airway hyperresponsiveness. Recently, more attention has been geared towards markers of inflammation including exhaled nitric oxide and sputum eosinophils. Subjective measures of asthma control include patient-derived parameters such as number of wheezing episodes, nocturnal symptoms, exercise-induced symptoms, short-acting beta-agonist use, steroid bursts, emergency-department visits, and hospitalizations. Asthma-related quality of life is related to asthma morbidity, and patients with better baseline quality of life have improved outcomes. Asthma-related costs include direct costs mostly comprised of hospitalizations and emergency-room visits, and indirect costs including school absenteeism. SUMMARY: There is no ideal outcome measure for evaluating pediatric asthma control, but each of these outcome measures must be used together to evaluate a patient at each outpatient visit. Patient-centered measures of asthma control must also be further incorporated into office visits for improved asthma management.     

Remodeling of the airway smooth muscle cell: are we built of glass?

Classical understanding of airway lumen narrowing in asthma has held that the isometric force generated by airway smooth muscle (ASM) must be at every instant in a static mechanical equilibrium with the external load against which the muscle has shortened. It has been established recently, however, that this balance of static forces does not apply in the setting of tidal loading as occurs during breathing and must give way to the broader concepts of (1). the perturbed contractile state that exists far from static equilibrium conditions and (2). mechanical plasticity of the ASM cell. Here we describe the hypothesis that the well-established static contractile state, the newly-elaborated perturbed contractile state, as well as the remarkable mechanical plasticity of the ASM cell, are all subsumed under a rubric that is at once surprising, unifying and mechanistic. The specific hypothesis suggested is that the ASM cell behaves as a glassy material [Phys. Rev. Lett. 87 (2001) 148102]. A glass is a material that has the disordered molecular state of a liquid and, at the same time, the rigidity of a solid. If the hypothesis is true, then the ability of the ASM cytoskeleton (CSK) to deform, to flow and to remodel would be determined by an effective temperature-called the noise temperature-representing the level of jostling (i.e. molecular noise or agitation) present in the intracellular microenvironment. The abilities of the CSK to deform, to flow and to reorganize represent basic biological processes that underlie a variety of higher cell functions. If supported by the data, therefore, this integrative hypothesis might have implications in medicine and biology that go beyond the immediate issues of smooth muscle shortening and its role in asthma.