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Inter and intra-observer variation in ultrasonographic detection of gallstones: the Multicenter Italian study on epidemiology of cholelithiasis (M.I.COL.).

Inter and intra-observer agreement in classifying the presence of gallstones by ultrasonographic images according to established criteria was studied. A film recording of 50 routine ultrasonographic examinations of the gallbladder was read by each of the 46 observers who participated in the Multicenter Italian Study on Epidemiology of Cholelithiasis (M.I.COL.). The overall Kappa score for inter-observer agreement was 0.649, while intra-observer agreement was "good" or "excellent" (Kappa scores greater than 0.60) in 75% of the observers. No statistical difference for inter-observer agreement between "novices" and "expert" echographers was found in the overall Kappa statistic or in category-specific Kappa scores (gallstone, no gallstone, doubtful and inconclusive examinations) The present study suggests that the development of explicit criteria by a group of trained echographers does not eliminate inter- and intra-observer disagreement in categorizing subjects for gallbladder stones.

Cholelithiasis

Observer variation in examination of knee joints.

The knees of 20 patients with rheumatoid arthritis were each examined on two occasions on the same morning by three observers. Assessments were made of joint warmth, synovial thickening, effusion, instability, quadriceps power, bony enlargement, range of movement, and knee circumference, and were graded on a scale of 0-4. Analysis of the results shows close intraobserver agreement for all measurements but considerable interobserver variation for all subjective measurements.

Arthritis, Rheumatoid

Observer variation in assessment of liver biopsies of alcoholic patients.

The aim was to construct a questionnaire analyzing pathological features possibly present in alcoholic liver disease, to assess its interobserver variation and to determine the influence of technical data on this variation. A total of 764 inpatients drinking 90 g (median) of pure alcohol per day for 25 years was observed; 402 patients were excluded because of associated nonalcoholic disease, refusal or contraindication to biopsy, leaving 362 patients included. Two pathologists independently analyzed each biopsy and completed a questionnaire including 41 items. Coefficient of concordance between observers was evaluated with the kappa statistic (k). The prevalence of 14 lesions was low, equal to or under 10%, leading to a nonsignificant concordance. For the 27 remaining features, two had an almost perfect degree of concordance (k greater than 0.81): presence of hepatocellular carcinoma and cirrhosis. Three had a substantial coefficient of concordance (k greater than 0.61): fibrous septa, size of cirrhotic nodules, and liver cell regeneration. Nine had a moderate (k greater than 0.41), 11 a fair (k greater than 0.21), and two a slight (k less than 0.21) coefficient of concordance. In terms of final diagnosis of alcoholic liver disease the concordance was substantial for cirrhosis with acute alcoholic hepatitis (k = 0.77), cirrhosis without alcoholic hepatitis (k = 0.75), acute alcoholic hepatitis without cirrhosis (k = 0.65) and normal liver (k = 0.64). Concordance was moderate for steatosis (k = 0.47) and slight for fibrosis alone (k = 0.16).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism

Observer variation in histologic classification of malignant and borderline ovarian tumors.

Eight hundred sixty-nine primary malignant or borderline ovarian tumors reported to the Norwegian Cancer Registry were reviewed. The histologic slides were randomly distributed to six observers and classified according to the World Health Organization classification of ovarian tumors. By rotation of slides, each tumor was successively reviewed by three observers. Each observer was given approximately 40 duplicates of slides he or she had typed before, mixed in with the slides for the third review. A contracted version of the classification with 27 entries was used in the analysis. Mean intraobserver reproducibility was 62% (kappa, 0.53), varying from 50% to 75% (kappa, 0.34 to 0.70) for the individual observers. The mean rate of agreement between two observers was 56% (kappa, 0.46), varying from 46% to 65% for the individual pairs of observers. The rate of full agreement among three observers was 41%. The most common disagreements were between different specific types of carcinoma, between undifferentiated and differentiated carcinoma, between borderline and malignant tumors, between unclassified and classified carcinoma, and between mixed and pure types of carcinoma. Very low reproducibility was obtained for mixed and unclassified carcinoma.

Carcinoma

Observer variation in the clinical diagnosis of mandibular pain dysfunction syndrome.

In preparation for a survey to investigate the prevalence of mandibular pain dysfunction syndrome (MDS) in a non-hospital group of individuals, the measure of agreement obtained by two observers when recording signs and symptoms of MDS in the same subjects was investigated. The criteria used for this purpose are defined. Two groups of subjects, 50 MDS patients and 50 individuals not complaining of the condition, were examined independently. Considerably more agreement between the two observers was reached with regard to patients than contrast subjects. Both observers showed more agreement in assessment during the opening movement of the mandible. It was suggested, therefore, that in order to reduce the observer error inevitably present during a survey, the signs and symptoms which manifest themselves during the opening movement of the mandible should be used to diagnose MDS rather than a more elaborate time-consuming technique.

Adolescent

Observer variation in the assessment of dysplasia in ulcerative colitis.

Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only 'fair' or 'moderate'. As expected, agreement over the two categories 'dysplasia' vs 'no dysplasia' was better, ranging from 68% to 84%, and for 'atypia present' (reactive atypia, low- and high-grade dysplasia) vs "no atypia' two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of "atypia, significance uncertain', so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Colitis, Ulcerative

Chemical basis of the electrophoretic variation observed at the alcohol dehydrogenase locus of Drosophila melanogaster.

The amino acid substitution responsible for the different electrophoretic mobility of the ADHs alleloenzyme and the ADHf alleloenzyme of the alcohol dehydrogenase from a Nigerian population of Drosophila melanogaster has been established as lysine (ADHs) for threonine (ADHf). This result is discussed with reference to the charge state model of electrophoretic variation, in conjunction with other know substitutions at this locus. It is concluded that electrophoretic methods should be capable of distinguishing many alleloenzymes which have identical isoelectric points without recourse to explanations involving conformational variability.

Alcohol Oxidoreductases

Comparison of four articular indices for use in clinical trials in rheumatoid arthritis: patient, order and observer variation.

Using a Latin square design, 4 patients were examined by 4 rheumatologists. Joints were scored for tenderness and inflammation. The Ritchie, the index of the American Rheumatism Association (ARA), the Hart modified Ritchie and a simplified Lansbury index were calculated from the raw data. The results suggest that an articular index consisting of a simple count of tender joints (Hart modified Ritchie) or a simple count of tender or swollen joints (ARA index) are the most reproducible with multiple observers. We suggest that these indices would be most appropriate for multicenter clinical trials.

Arthritis, Rheumatoid

Observer variation in assessing spinal curvature and skeletal development in adolescent idiopathic scoliosis.

Accurate measurements of spinal curvature and skeletal development are crucial in planning treatment and assessing curve progression in adolescent idiopathic scoliosis (AIS). An inter-rater agreement trial was undertaken to estimate the reliability of measuring these spinal parameters. Two orthopaedic surgeons and two trained technicians from a scoliosis clinic independently read 30 anteroposterior roentgenograms of AIS patients. Skeletal maturity was assessed using the six-point Risser sign scale, and spinal curvature was measured using the method of Cobb. Excellent agreement was observed in evaluating Risser signs (Kappa = 0.8) and primary Cobb angles (intra-class correlation coefficient, Rho = 0.98). The standard deviation of inter-observer error in measuring primary Cobb angles was 2.5 degrees, and the intra-reader error, based on one observer's reassessments of 15 films, was 1.9 degrees. Inter-rater agreement for assessing secondary Cobb angles was much lower (Rho = 0.52) because small curves (less than 20 degrees) were often not noticed. Differences in agreement between surgeons and technicians were relatively minor. These results indicate that personnel trained at this clinic are able to assess these spinal parameters reliably.

Adolescent

Observer variations in the diagnosis of stroke. WHO collaborative study on the control of stroke in the community.

Validity and consistency of the diagnosis of stroke and its types were tested with 60 case reports including 15 diguised duplicates, drawn at random from community-based stroke registers. Seven European, 5 Japanese, and 5 other centers participated the test. The diagnosis of stroke as such (regardless of its type) seems to have been established accurately in all the 3 groups of centers; this leads to the conclusion that the incidence rates of stroke as registered in the participating centers were comparable. The diagnosis of the types of stroke was less reliable, since intra-and inter-observer bias was found in the diagnosis of the identical sample of test cases. In some European centers, the type of stroke was rarely determined, unless objective and definitive evidences were available. The Japanese centers appeared to have diagnosed the type of stroke in a relatively more uniform way between centers, however, the consistency of the diagnosis at separate times was lower. Subarachnoid hemorrhage, when diagnosed, was generally based on firmer gounds. These observations were confirmed in a small number of autopsy-verified cases. These varying diagnostic attitudes introduce false differences. Such "softness" of type-diagnosis must be borne in mind when comparison of type of stroke at different times or between populations is attempted.

Cerebral Hemorrhage

Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia.

To assess the variability among histopathologists in diagnosing and grading cervical intraepithelial neoplasia eight experienced histopathologists based at different hospitals examined the same set of 100 consecutive colposcopic cervical biopsy specimens and assigned them into one of six diagnostic categories. These were normal squamous epithelium, non-neoplastic squamous proliferations, cervical intraepithelial neoplasia grades I, II, and III, and other. The histopathologists were given currently accepted criteria for diagnosing and grading cervical intraepithelial neoplasia and asked to mark their degree of confidence about their decision on a visual linear analogue scale provided. The degree of agreement between the histopathologists was characterised by kappa statistics, which showed an overall poor agreement (unweighted kappa 0.358). Agreement between observers was excellent for invasive lesions, moderately good for cervical intraepithelial neoplasia grade III, and poor for cervical intraepithelial neoplasia grades I and II (unweighted kappa 0.832, 0.496, 0.172, and 0.175, respectively); the kappa value for all grades of cervical intraepithelial neoplasia taken together was 0.660. The most important source of disagreement lay in the distinction of reactive squamous proliferations from cervical intraepithelial neoplasia grade I. The histopathologists were confident in diagnosing cervical intraepithelial neoplasia grade III and invasive carcinoma (other) but not as confident in diagnosing cervical intraepithelial neoplasia grades I and II and glandular atypia (other). Experienced histopathologists show considerable interobserver variability in grading cervical intraepithelial neoplasia and more importantly in distinguishing between reactive squamous proliferations and cervical intraepithelial neoplasia grade I. It is suggested that the three grade division of cervical intraepithelial neoplasia should be abandoned and a borderline category introduced that entails follow up without treatment.

Biopsy

Observer variation in the pathologic diagnosis of malignant lymphoma in Canada.

Biopsies from "poor prognosis" non-Hodgkin's lymphomas were studied to assess diagnostic variations among pathologists. The original diagnosis and the diagnoses of a nationwide panel of local reference pathologists (LRPs) from 104 cases were reviewed and the technical quality of each biopsy evaluated. Using a modified Rappaport classification, there was agreement in 57% of cases among the panel. This increased to 84% when diagnoses were grouped according to Working Formulation grades. Of the 90 cases in which a comparison of the contributing pathologist's diagnosis and the most common panel diagnosis was possible, there was exact agreement in 51% (kappa = 0.311) of cases and agreement regarding WF grade in 68% (kappa = 0.318). Major panel disagreements occurred in 26 (25%) cases, involving the distinction of metastatic anaplastic carcinoma or Hodgkin's disease from non-Hodgkin's lymphoma in 17 cases and follicular versus diffuse architecture in 16 (overlap present). The contributing pathologist had a major disagreement with the panel in 18 cases (20%), of type and frequency similar to those within the panel itself. Poor fixation (complete or partial) was present in 49 cases (47%); this resulted in significantly fewer majority agreements than in the well-fixed group (25% versus 60%, P = 0.020) and also increased rates of disagreement in the diagnosis of lymphoma versus anaplastic carcinoma. Thus improvements in the technical quality of biopsy material could further improve the diagnostic accuracy of lymphoma diagnosis.

Female

The pineal gland of the mole (Talpa europaea L.). II. Ultrastructural variations observed in the pinealocytes during different parts of the sexual cycle.

Changes of some ultrastructural parameters (paracrystalline structures, Golgi apparatus, secretory granules) in mole pinealocytes were quantitatively studied during the various phases of the sexual cycle. An increase in quantity of paracrystalline structures and of the Golgi appratuses was demonstrated during the period of high sexual activity in male pinealocytes and during oestrus, gestation and lactation in female pinealocytes. Moreover, the appearance of vacuoles in female pinealocytes was observed during pro-oestrus. These results seemto demonstrate close relationship between the endocrine activity of the hypophyseo-gonadal axis and the synthesis of some compounds by the pinealocytes. No increase in the quantity of secretory granules was observed during the various phases of the sexual cycle studied. Key words: pinealocytes, mole, sexual cycle, ultrastructure, paracrystalline structure.

Animals

Dysplasia and deoxyribonucleic acid aneuploidy in the assessment of precancerous changes in chronic ulcerative colitis. Observer variation and correlations.

Cancer prevention in patients with long-standing ulcerative colitis depends on the detection of epithelial dysplasia in colorectal biopsy specimens. Deoxyribonucleic acid analysis by flow cytometry has also been used to examine biopsy specimens, and might be a more quantitative method of detecting precancerous change. Histology and flow cytometry were used to analyze 333 paraffin blocks from colectomy specimens of 58 patients with extensive ulcerative colitis; 22 of these patients had developed carcinoma. Interobserver agreement between three experienced pathologists grading the sections was good for high-grade dysplasia and no dysplasia, but poor for low-grade and indefinite dysplasia. Deoxyribonucleic acid aneuploidy was easier to recognize than dysplasia and, as with dysplasia, it was found to be associated with patients who had developed carcinomas. The presence of deoxyribonucleic acid aneuploidy correlated with the presence of dysplasia. We believe that dysplasia is a useful marker of premalignant change and that flow cytometry may be useful as a complement to histologic examination when dysplasia is suspected.

Adult

Observer variation in the diagnosis of dysplasia in Barrett's esophagus.

The potential value of biopsy surveillance of patients with Barrett's esophagus for dysplasia is diminished by a lack of agreement on the diagnostic criteria for dysplasia. In a preliminary consensus conference, experienced gastrointestinal pathologists from four medical centers agreed on criteria for a five-tiered histologic classification of dysplasia in Barrett's esophagus--negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and intramucosal carcinoma. Eight morphologists in the four centers tested the criteria for interobserver agreement by examining a set of coded slides that had been chosen to include some especially difficult interpretative problems in all five histologic classifications. Interobserver agreement of 85 and 87% was achieved in successive reviews when the combined group of high-grade dysplasia and intramucosal carcinoma was compared with the combined group of low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia. Comparison of other groups yielded less agreement. For example, negative for dysplasia could be distinguished from all other diagnoses with an interobserver agreement of 72%. We conclude that experienced gastrointestinal morphologists can diagnose high-grade dysplasia and intramucosal carcinoma with a high degree of agreement and thus can detect those patients who may need immediate rebiopsy or esophageal resection. Either further refinement of histologic criteria or alternate diagnostic methods will be needed to achieve the reproducible diagnosis of indefinite changes and low-grade dysplasia. This is important because patients with such changes theoretically merit closer endoscopic surveillance.

Barrett Esophagus