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Regional observer performance variation in the evaluation of gated cardiac blood pool studies.

Receiver operating characteristic (ROC) analysis demonstrated that regional variations of sensitivity exist in the detection of wall motion abnormality in cardiac blood pool imaging studies. The observer response is significantly better in the apex than either the septum or posterolateral wall segments. The observer errors tend to be false-negative in the posterolateral wall segment and false-positive in the other two segments. Image presentation can make a significant difference to the overall sensitivity, and the monochrome cine-sequence performed best in this study.

Gated Blood-Pool Imaging

An assessment of disability rating scales used in multiple sclerosis.

Twenty patients with clinically definite, stable multiple sclerosis were examined independently by three of us at the same visit and given scores on the Ambulation Index, Expanded Disability Status Scale, and Kurtzke Functional System scales. Observer error accounted for 12% to 55% of the variation observed between individual Kurtzke Functional System scores, 17.1% of the variation observed between the patients' Expanded Disability Status Scale scores, and only 3.9% of the variation between Ambulation Index scores. The implications of these findings for the choice of scales in clinical trials are described.

Adult

[Observer agreement in the measurement of leg length].

The lower limb length measurement is an important element for the diagnosis of mechanical or structural lumbar pain. Also it has been used for referral pain associated with hip or knee osteoarthritis or the groin and suprapubic areas. The aims of the present study were: 1) to measure the intra and inter observers variation; 2) to measure the intra-method variation using two different techniques for lower limb length measurement, one called the "apparent measure" (9) and comparing both with the radiological measurement technique. Two medical doctors, training on the techniques for lower limb measurement, performed the measurements. The exclusion criteria were flexion deformity of the hip or an overweight greater than 20% over the mean weight expected according to age and sex. A correlation coefficient and its 95% confidence interval (CI) were estimated, one tail test (Ho: r = 0.75). Seventeen patients fulfilled the inclusion criteria, 15 females and two males. The mean age was 35.8 years +/- 13.0 (SD). The correlation coefficient for the inter-observers variation using the "apparent measure" was 0.99 (CI = 0.985) and for the difference between legs it was 0.88 (CI = 0.10). The inter-observers variation for lower limb length measurement using the technique of "real measure" showed a correlation coefficient of 0.77 (CI = 0.95) and for the difference in length between legs it was 0.99 (CI = 0.85). The intra-observer correlation coefficient was 0.95 (CI = 0.85). The correlation coefficient for the inter-observer using the X-ray pictures was 0.98 (CI = 0.92).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Coding of cause of death for mortality statistics--a comparison with results of coding by various statistical offices of West Germany and West Berlin].

1.136 death certificates representing all 1985 Bremen cardiovascular deaths and a 50%-sample of non-cardiovascular deaths in the age group 25-69 years were analyzed for reliability of nosologists' coding according to ICD-coding rules (9th revision). The 1.136 photocopied death certificates were used to assess intra-observer-variation in Bremen and to determine inter-observer-variation among 7 nosologists from 6 different State Statistical Offices and the Federal Statistical Office. Intra-observer-agreement in Bremen was found to be similar to the results presented in a comparable US-study: Bremen: 92.1%; Curb et al. 1983: 94.8%-96.1%; 3-digit-ICD-Code. Inter-observer-agreement was found to be much lower in Germany than in two US-studies: 3 coders agreeing on 3-digit-ICD-Code: Bremen: 67.7% (average, 3 coders out of 7); Curb et al.: 90.2% (3 coders); 3 coders agreeing on 4-digit-ICD-Code: Bremen: 61.5%; NCHS 1980: 90.3%. Agreement-rates were also much lower in Germany than in the USA (Curb et al.) when particular disease groups were analysed: Ischaemic heart disease (ICD 410-414): Bremen: 82.7% (average); USA: 97.2%; cerebrovascular disease (ICD 430-438): Bremen 65.6% (average); USA: 93.2%; neoplasms (ICD 140-239): Bremen: 94.0% (average); USA: 97.8%. We conclude that training, individual characteristics of nosologists, and other factors may cause important artifacts when comparing German mortality statistics on a regional level or during different time intervals.

Berlin

Precision of Larsen grading of radiographs in assessing progression of rheumatoid arthritis in individual patients.

A study was designed to evaluate observer variation in the assessment of radiographic deterioration of individual patients using the Larsen grading system. Radiographs of hands and feet of 52 patients were assessed by three observers. Each patient had paired films taken one year apart which were assessed together for change in score. To assess within-observer variation each set of films was read twice by all observers. The average progression was 11.6 (SD 9.0). Analysis of the source of variation showed the single observer replication SD to be 3.7 but that for different observers to be 5.5. This may be interpreted as indicating that to achieve 95% confidence of detecting a true change an increase in Larsen score of 8 is required if the same observer assesses or up to 11 if a different observer assesses.

Arthritis, Rheumatoid

The reduction of inter- and intra-observer variability for defining regions of interest in nuclear medicine.

The use of region-of-interest (ROI) techniques to quantify data obtained in radionuclide images is commonplace. However, the reproducibility of quantitation due to inter- and intra-observer variations using particular methods of deriving ROIs is often not appreciated. We examined such variations in the results obtained by four independent observers of varying experience using four methods of depicting a ROI about an organ. The set of image data consisted of renal scans with varying target-to-background ratios, and the ROI facilities included two edge-detection methods. The results indicated that, once observers were experienced with edge-detection methods, a lower inter- and intra-observer variation could be achieved, although the technique of 'shrinking' a ROI about a subjectively chosen display level was reasonably satisfactory. In terms or reproducibility, the least satisfactory method of depicting a ROI was the commonly used manually guided 'bug' around arbitrarily chosen display levels representing the boundary of an organ.

Humans

The fetal heart rate trace is normal, isn't it? Observer agreement of categorical assessments.

The limitations of the kappa statistic method to measure inter-observer variation of categorical assessments are shown by means of a hypothetical example. Another method for assessing the inter-observer variation of categorical variables, the proportion of agreement, is used for the same example, and reasons why it is preferable to the kappa statistic are given. Since this method allows measurement of the inherent difficulty of carrying out a particular assessment, it has wide applicability in the introduction of new technology. If a proportion of agreement study shows poor inter-observer agreement for a new method, the technology must either be improved or abandoned.

Bias

Reproducibility of goniometry of the wrist.

The wrist motion in 31 healthy probands was measured by four observers with a simple goniometer under standardized conditions. The INTRA-observer variation was calculated to 5 to 8 degrees and the INTER-observer variation to 6 to 10 degrees. No difference between experienced and non-experienced observers was found. The difference between the right and the left wrist was negligible, indicating that the opposite wrist can be used as reference when evaluating restrictions in motion.

Adult

Interobserver variability in the interpretation of contrast venography, technetium-99m red blood cell venography and impedance plethysmography for deep vein thrombosis.

Contrast venography (CV) is the standard technique for diagnosing deep vein thrombosis (DVT). Newer noninvasive tests have also proven efficacious. However, there is a lack of data on the level of agreement among observers in their interpretation of the results of the various tests. After agreeing on well-defined criteria, three experienced observers assessed, blindly, the results of tests performed over a 4-month period on 117 patients who were suspected clinically of having had a first episode of DVT. The kappa statistic was used to measure the level of agreement beyond chance for CV (69 patients), red blood cell venography (RBCV) (82 patients) and impedance plethysmography (76 patients). The results of CV were assigned to normal, abnormal or inadequate categories, and those of RBCV and IPG to normal, equivocal or abnormal categories. The kappa values for CV, RBCV and IPG ranged from 0.53 to 0.56, 0.42 to 0.56 and 0.90 to 0.91 respectively. Values greater than 0.75 represented excellent agreement beyond chance and those between 0.40 and 0.75 represented fair to good agreement. Excellent kappa values were obtained for IPG because interpretation of the results of this method is entirely objective. Although the values for CV and RBCV showed good to fair agreement, there was a greater degree of observer variation, despite the well-defined criteria, indicating the subjectivity of interpretation of these test results. It is concluded that the kappa statistic can be used to measure observer variation of the results of tests for diagnosing DVT and may serve as a quality control tool for studies in which more than one person interprets the results.

Contrast Media

Leg length inequality measured by ultrasound and clinical methods.

Leg length inequality (LLI) was determined by ultrasound and two clinical methods in 100 subjects without previous disorders of the lower extremities. The mean LLI by ultrasound was 4.1 mm (range: 0-16 mm). An LLI of 10 mm or more was found in 4% of the subjects. The mean inter-observer variation by ultrasound was 0.9 mm (range: divided by 5-8 mm), which was significantly less than that obtained by clinical methods. The 95% confidence interval of inter-observer variation (+/- 2 SD) by ultrasound was +/- 5 mm and this interval is assumed to represent the accuracy of the method. Because LLI measurement by ultrasound is more reliable than clinical methods, ultrasound is recommended for routine use in clinical practice.

Adolescent

Two-hydronic-reactive states of acetylcholinesterase, mechanistically relevant acid-base catalyst of pKa 6.5 and a modulatory group of pKa 5.5.

Variation of experimentally observed pKa values in pH-dependent kinetic studies using acetylcholinesterase (AcChE) is rationalized by proposal of two-hydronic-reactive states, EH and EH2, of the free AcChE molecule. Two kinetically influential ionizations with pKa 6.5 for the general acid-base catalyst, possibly the imidazole group of histidine, and a modulatory group with pKa 5.5 residing at the juxtaposal modulatory site, provided fundamental bases for the observed variation in pK(app) values. Appropriate equations applicable to the proposed kinetic model in conjunction with pKa values (pKI 5.5, pKII 6.5) and relative varied values of the pH-independent rate constants, k'cat/K'm and kcat/Km, of the reactive states were used to generate computer simulation error-free pH-rate profiles. A series of theoretical apparently simple sigmoidal pH-rate profiles with characterizing parameters pK(app) varying between 5.5-6.5 were obtained. Ionization of a modulatory group with pKa 5.5 alone modifies the reaction mechanism of AcChE, and binding of substrates and inhibitors at this site provides modulation of catalysis/binding at the active center. Analysis of the relative magnitudes of pH-independent rate constants for the two reactive states revealed that in terms of the overall catalysis, the EH state shows favorable reactivity towards the cationic reagents with reactivity 1.0, as compared to the EH2 state with reactivities 0.25-0.55. Neutral reagents, in general, make use of the EH2 state more than cationic reagents, with reactivities 1.0 for the EH state and 0.3-1.0 for the EH2 state. Further analysis showed that this discrimination between the two reactive states, by both types of reagents, occurs predominantly through the difference in binding constants K'm and Km. Relative binding of a given cationic reagent to the respective reactive states ranges from K'm = 1.8 X Km to 4.0 X Km, and from K'm = 1.0 X Km to 2.0 X Km for the neutral reagents.

Acetylcholinesterase

An international collaborative study on foot and mouth disease virus assay methods. 2. Quantification of 146S particles.

Workers in 11 laboratories in Europe and one in North America participated in a collaborative study to assess the variability of a sucrose gradient procedure used for the quantification of foot and mouth disease virus (FMDV). To this end, a range of standards was distributed from one of the participating laboratories. A series of adenine preparations were used to assess the various spectrophotometers/UV monitors and it showed most to be accurate and linear in their responses. The FMDV and MS2 ribophage standards were used to assess the sucrose gradient procedure and indicated low levels of within laboratory variation whereas between laboratory variation was greater. Recalculation of results from the unprocessed data in the coordinating laboratory permitted the identification and reduction of one source of between laboratory variation. Despite the observed variations, the results indicated that meaningful comparisons could be made between the data of different laboratories provided that a procedure similar to the one described in this report is used.

Adenine

Sequential mutations in hemagglutinins of influenza B virus isolates: definition of antigenic domains.

Comparative analysis of the amino acid sequences of hemagglutinins (HAs) of influenza B/Lee/40, B/Md/59, and B/HK/73 viruses has allowed examination of the molecular basis of antigenic variation in type B viruses. As seen with influenza type A viruses, antigenic drift in influenza B viruses proceeds mostly through the accumulation of amino acid substitutions within the HA1 portion of the HA molecule. However, the rate of variation observed among the influenza B virus HAs appears to be significantly lower than the observed rate of variation among influenza A virus HAs. The overall rate of amino acid change in the HA1s of the influenza B viruses studied is 2% per 10 years, whereas the HA1s of H3 influenza A viruses vary by 9.2% per 10 years. The sequences of the influenza B HAs were also examined in relation to the three-dimensional model for the A/Aichi/2/68 HA. When the primary amino acid sequences are compared, it appears that most of the important structural features of the type A HAs--such as the sialic acid binding site, the disulfide linkages, and the stem structure of the trimer--are conserved in the influenza B virus HAs. Regions are also identified where extensive amino acid substitutions have occurred among the three antigenically distinct influenza B virus HAs. The locations of these areas in the B HA structure correspond to antigenic regions proposed for the A virus HAs. In addition, modulation of antigenic regions in B virus HAs may also occur through amino acid deletions and variation in glycosylation sites.

Amino Acid Sequence

Strain-cross response of heavy male broilers to dietary lysine in the finisher feed: live performance and further-processing yields.

A total of 2,560 male broilers from eight commercial strain-crosses were growth to 42 days of age on common starter (1 to 21 days; 23.06% CP, 3,217 kcal ME/kg) and grower (21 to 42 days; 20.14% CP, 3,224 kcal ME/kg) rations. All strain-crossed subsequently received finisher diets (17.95% CP; 3,186 kcal ME/kg) containing either .85 or .95% lysine from 42 to 53 days of age. Further-processing yields were determined on 12 birds per pen, selected within +/- 10% of the replicated pen (8 pens per strain-cross, 40 birds per pen) average weight. The strain-crosses differed significantly (P less than .05) in BW (1, 21, 42, and 53 days), weight gain (WG), feed:gain ratio (1 to 21 and 21 to 42 days), and mortality rate (1 to 21 days). The lysine effect during the finisher period was significant for 53-day BW and WG from 1 to 53 days. Chilled carcass (CC) and abdominal fat (AF) weights, CC yield (percentage, excluding AF), AF yield (percentage of CC weight), Pectoralis major, Pectoralis minor, total deboned breast (TDB), drumstick, thigh, wing, and residual "cage" and skin yields varied among the strain-crosses. A significant weight and yield response to lysine was observed for TDB. Variation observed among strain-cross in live performance, further-processing yields, and response to additional lysine is attributed to differences in rate of growth and degree of maturity at market age. Furthermore, the lysine requirement during the finisher period for optimum breast meat yield may be higher than that recommended by the National Research Council in 1984.

Adipose Tissue

Some observations on variations in filament overlap in tetanized muscle fibres and fibres stretched during a tetanus, detected in the electron microscope after rapid fixation.

Anomalous tension development which would not be predicted from the descending limb of the length-tension curve occurs during prolonged tetani and after stretch during a tetanus. Variations in filament overlap might account for all or part of the tension enhancement. Fibres isolated from frog skeletal muscle were rapidly fixed during a tetanus with mercuric chloride in ethanol and chloroform so that the correct alignment of the filaments in the overlap zones was preserved. The fibres were examined in polarized light with compensation, and in the electron microscope. There were variations in striation spacing along the length of the fibres, and severe shortening with contraction bands near the tendon insertions, confirming observations made by others on live fibres. Many variations in filament overlap which would not be detectable by light microscopy or laser diffraction were seen in the electron microscope. In a pilot study we measured differences in the width of the overlap zones between half-sarcomeres in a small area and within individual half-sarcomeres. In the latter case the variations were greater in a fibre which developed creep of tension and one which did not. Even greater variations were seen in three fibres stretched during a tetanus, and, in two of these, there were some grossly elongated half-sarcomeres in which the filaments had pulled out of the overlap zones, leaving gaps.

Animals

Inter-observer agreement and clinical diagnosis of leprosy for prophylaxis studies.

Clinical diagnosis is still the most useful tool for detecting early cases of leprosy in field research. In prophylaxis studies accuracy of clinical diagnosis of leprosy is important during intake as well as for measuring efficacy of the intervention. This paper reports our observations regarding the extent of inter-observer variations in clinical diagnosis of leprosy and its implications for a prophylaxis study. Information on 225 suspects and cases of leprosy, each examined independently by three senior workers after initial standardization, was used for this purpose. Agreement among the examiners regarding the presence of skin patch, thickened nerve trunk and sensory deficit was fairly high (Kappa = 0.7). Agreement on the presence of infiltration in a skin patch was not satisfactory (Kappa = 0.4-0.5). It was observed that in clinical diagnosis of leprosy, presence of skin patch and sensory deficit, as well as thickened nerve trunk and related anaesthesia were correlated observations. The influence of inter-observer variations on defining leprosy problem in the community can be quite large. The paper suggests some ways of overcoming the problem.

Adult

Pitfalls in the diagnosis of recurrent ulceration after surgery for peptic ulcer disease.

We have studied the accuracy of diagnostic methods in achieving a diagnosis in 75 patients with 81 proven episodes of recurrent ulceration. When the endoscopic findings did not permit an accurate diagnosis, radiology usually provided no additional information. The sensitivity of a combined diagnostic approach was not different from that of endoscopy alone, and so the routine use of upper GI radiographs in addition to endoscopy should, therefore, be abandoned. We also assessed observer variation among endoscopists prospectively in 38 patients investigated for dyspepsia after operation for peptic ulcer. Major observer variation in diagnosing suspected recurrent ulceration occurred in 11% of patients, with a sensitivity and specificity higher than 77 and 94%, respectively. As not all the postoperative gastroduodenojejunal mucosal breaches are peptic, we suggest that acid output and enterogastric reflux assessments are useful diagnostic adjuncts to endoscopy.

Deglutition Disorders

Systematic oserver variation in trachoma studies.

There has been increasing awareness in recent years among trachomatologists, as well as among workers in other fields of medical research, of the frequency and importance of observer variation in epidemiological studies and clinical trials. In trachoma, the lack of simple definitive laboratory diagnostic procedures suitable for wide application has placed the onus largely, and usually exclusively, on clinical observation.The study reported is based on the recorded observations of two skilled ophthalmologists in an epidemiological survey covering more than 35 000 persons in Taiwan. Observer differences were found to lie not only in deciding whether a case is trachomatous or not but also in assigning cases diagnosed as trachoma to the appropriate evolutive stage of the WHO trachoma classification.THE CONCLUSIONS REACHED ARE THAT: (a) inter- and intra-observer variations of some degree are inevitable if dependence is placed on clinical examination alone; (b) it is possible by preliminary testing of observers' interpretation of clinical signs to determine the nature of these differences, to assess their importance, and to reduce them; also to set base-lines for the detection of subsequent divergences over time; and (c) it is better to have two observers than one in any trachoma survey or clinical trial.

Adolescent