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Interobserver reproducibility of histopathologic prognostic variables in primary cutaneous melanomas.

BACKGROUND: The prognosis for patients with localized primary cutaneous melanoma is known to depend principally on tumor thickness, and to a lesser extent on ulcerative state and Clark level. We have recently found in an analysis of 3661 patients that tumor mitotic rate (TMR) is also an important prognostic parameter, ranking second only to tumor thickness. However, few studies have assessed the accuracy and reproducibility with which these features of a melanoma are recorded by histopathologists. AIM: To assess interobserver reproducibility of major pathologic prognostic parameters in cutaneous melanoma. METHODS: Single hematoxylin and eosin-stained slides of 69 dermally invasive primary cutaneous melanomas were circulated among six pathologists with differing experience in the assessment of melanocytic tumors. The observers independently determined the tumor thickness, Clark level of invasion, ulcerative state, and TMR for each lesion. Intraclass correlation coefficients and kappa scores for multiple ratings per subject were calculated. RESULTS: The intraclass correlation coefficients were 0.96 for tumor thickness and 0.76 for TMR. The kappa scores were 0.83 for ulcerative state and 0.60 for Clark level. These results indicated excellent agreement among the pathologists for measurements of tumor thickness, ulcerative state, and TMR and fair to good agreement for Clark level. CONCLUSIONS: Appropriately trained and experienced histopathologists can assess prognostically important features of melanomas accurately and reproducibly. Given our recent finding of the significance of TMR in determining prognosis, it is important that this feature be assessed by a standardized method and documented for all primary cutaneous melanomas.

Humans↗

Reproducibility and validity of an extensive semiquantitative food frequency questionnaire among Greek school teachers.

We evaluated the reproducibility and validity of a 190-item semiquantitative food frequency questionnaire (FFQ) to be used in a large prospective study in the Athens area of Greece. Eighty persons, 42 men and 38 women, ages 25-67 years, completed a self-administered FFQ, followed by monthly 24-hour diet recalls and then a second FFQ 1 year after the first. Correlation coefficients measuring the reproducibility and validity of the FFQ indicate that the questionnaire is reproducible and provides a reasonably reliable measure of intake for many nutrients over a period of 1 year.

Adult↗

Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals.

We assessed the reproducibility and validity of a self-administered physical activity questionnaire used in a prospective study of 51,529 men. The questionnaire was administered by mail twice to 238 participants 2 years apart. During this interval, the participants completed a past-week recall and a 1-week activity diary at four times corresponding to different seasons throughout a year. Also, a step test was taken by a subset of the study participants. The intraclass correlation coefficients used to measure reproducibility were 0.39 for inactivity, 0.42 for nonvigorous activity, and 0.52 for vigorous activity. The correlations between diary-based and questionnaire-based activity scores, adjusted for variation in the diary measurements, were 0.41 for inactivity, 0.28 for nonvigorous activity, and 0.58 for vigorous activity. The distribution of activity scores was similar between the questionnaires and the average of past-week recalls, indicating the participants' ability to incorporate seasonal variation into their recall on a questionnaire. The correlation between vigorous activity and resting pulse was -0.45, whereas, for the pulse rate after stepping, the correlation was -0.41. These data indicate that this physical activity questionnaire is reproducible and provides a useful measure of average weekly activity, particularly vigorous activity, over a 1-year period.

Adult↗

A reproducible model of thromboembolic stroke in mice.

AN experimental mouse model of thromboembolic stroke is presented, in which standardized fibrin-rich emboli (150 microm diameter, 1.5 mm or 4 mm length) are injected into the internal carotid artery. Injection of six or eight 1.5 mm clots (corresponding to 0.16 or 0.21 microl clot material) led to a variable decrease in laser Doppler flow (LDF), but did not result in reproducible infarcts of the middle cerebral artery (MCA) territory, as determined by triphenyltetrazolium chloride (TTC) staining 24 h after embolization. Injection of ten 1.5 mm clots (0.27 microl) or four 4 mm clots (0.28 microl), however, caused a persistent LDF decline to about 20-30% of baseline and led to reproducible infarcts covering the entire MCA territory. The method establishes a clinically relevant, reproducible stroke model for the study of molecular mechanisms of ischemic brain injury in genetically engineered mice.

Animals↗

Reproducibility of the peritoneal equilibration test in CAPD patients.

A study was undertaken to evaluate the short-term reproducibility of peritoneal equilibration test (PET) results. Nine patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis underwent PETs under similar conditions on 2 consecutive days. Dialysate samples were obtained at 0 hours, midcycle, and at the end of exchange. There were no significant differences between the mean ratios at 4 hours for creatine, urea nitrogen, potassium and protein, and glucose between PET 1 and PET 2. A standard PET is highly reproducible when repeated under similar conditions. Reproducibility is better for ratios of creatinine, glucose, urea nitrogen, and potassium than for protein.

Aged↗

Indicator amount, temperature, and intrinsic cardiac output affect thermodilution cardiac output accuracy and reproducibility.

OBJECTIVE: To determine the accuracy and reproducibility of four thermodilution indicators (5-mL room temperature, 10-mL room temperature, 5-mL iced, and 10-mL iced injectates) at clinically relevant flow rates. DESIGN: Quasi-experimental study. SETTING: Animal research laboratory of a health sciences university. SUBJECTS: Six virgin western-breed ewes. INTERVENTIONS: Data were collected from six ewes that had ascending aorta electromagnetic flow probes and inferior vena cava occluders. Cardiac output was manipulated by inferior vena cava occlusion and isoproterenol infusion. Four thermodilution indicators were tested at high and low levels of cardiac output and compared with the electromagnetic flowmeter measurements of cardiac output. MEASUREMENTS AND MAIN RESULTS: The indicator amounts were determined from both injectate volume and temperature difference between the injectate and blood. Using 5-mL room temperature injectate as a reference, 10-mL room contained 2 x, 5-mL iced 2.1 x, and 10-mL iced 4.1 x the indicator amount of 5-mL room temperature injectate. Approximately 210 simultaneous thermodilution and electromagnetic flow measurements were made for each injectate over a flow range of 1.5 to 15.7 L/min. For the entire cardiac output range, systematic error was not present. However, the r2 value (.92) for the 10-mL iced injectate group was greater (p < .05) than that value (.79) for the 5-mL iced injectate group, while r2 values were .79 for the 10-mL room temperature group and .49 for the 5-mL room temperature group. At flow rates of < 4.7 L/min, r2 was not different among injectates, but reduced indicator amounts progressively overestimated output (p < .05), reaching 21% for the 5-mL room temperature group. At flow rates of > 7.7 L/min, the r2 value (.81) for the 10-mL iced group was greater (p < .05) than that value (.45) for the 5-mL iced group, while r2 values were .24 for the 10-mL room temperature group and .08 for the 5-mL room temperature group. Systematic error was not present. CONCLUSIONS: At low cardiac output levels, reduced indicator impairs accuracy but not reproducibility, a phenomenon that is perhaps related to indicator loss. At high cardiac output rates, reduced indicator impairs reproducibility. This phenomenon is probably related to low signal-to-noise ratio. Thermodilution indicator amounts should be tailored to the output range.

Animals↗

Alpha spectormetry measurement reproducibility study for uranium, plutonium, and americium in water at Rocky Flats environmental technology site.

An evaluation of alpha-spectrometry measurement reproducibility of low level 241Am, 239pU, 238U, and 234U concentrations in surface and ground waters at the Rocky Flats Environmental Technology Site was performed using the known and measured values of laboratory control samples. Tile purpose of the evaluation was to determine the lower limits of reliable quantitative measurement performed on recent surface water samples and historic ground water samples using alpha spectrometry. At known concentrations between 0.1 and 30 pCi L(-1) (3.7 x 10(-3) to 1.11 Bq (L-1)), the reproducibility is dependent on the magnitude of the measurement and is quantifiably reproducible to one significant figure.

Americium↗

Volumetric quantification of coronary artery calcifications using dual-slice spiral CT scanner: improved reproducibility of measurements with 180 degrees linear interpolation algorithm.

PURPOSE: The purpose of this work was to determine the reproducibility of coronary total calcium score (TCS) with dual-slice helical CT and compare three acquisition protocols. METHOD: Fifty patients (59 +/- 10 years old) underwent dual-slice helical CT (collimation = 2 x 2.5 mm) and coronary angiography. Two successive scans were performed, resulting in three sets of images: pitch = 1, 360 degrees linear interpolation (LI) (A360); pitch = 1, 180 degrees LI (A180); and pitch = 1.5, 180 degrees LI (B180). TCS values, calculated using a volumetric method with a threshold of 90 HU, were compared, and the interscan variation was determined. Diagnostic performances were compared with receiver operating characteristic curves. RESULTS: Protocol A360 provided significantly lower TCS than protocols A180 and B180 (p < 0.0001). No statistical difference was seen between A180 and B180, which provided the lowest interscan variation (40 +/- 58%). However, no significant clinical impact of the observed interscan variations was found. CONCLUSION: Reproducibility of TCS with dual-slice helical CT is improved by the 180 LI algorithm. However, dual-slice helical CT is not sufficiently reproducible to allow serial quantification of TCS over time.

Adult↗

Dixon quantitative chemical shift MRI for bone marrow evaluation in the lumbar spine: a reproducibility study in healthy volunteers.

PURPOSE: The purpose of this work was to explore the reproducibility of fat-fraction measurements using Dixon quantitative chemical shift imaging (QCSI) in the lumbar spine (L3, L4, and L5) of healthy volunteers. METHOD: Sixteen healthy volunteers were examined at 1.5 T two times to obtain a repeated measurement in the same slice and a third time in three parallel slices. Single slice, two point Dixon SE (TR/TE 2,500/22.3) sequences were used, from which fat-fraction images were calculated. The fat-fraction results are presented as averages over regions of interest, which were derived from the contours of the vertebrae. Reproducibility measures related to repeated measurements on different days, slice position, and contour drawing were calculated. RESULTS: The mean fat fraction was 0.37 (SD 0.08). The SD due to repeated measurement was small (sigmaR = 0.013-0.032), almost all of which can be explained by slice-(re)-positioning errors. CONCLUSION: When used to evaluate the same person longitudinally in time, Dixon QCSI fat-fraction measurement has an excellent reproducibility. It is a powerful noninvasive tool in the evaluation of bone marrow composition.

Adipose Tissue↗

Reproducibility of gastric myoelectrical activity and the water load test in patients with dysmotility-like dyspepsia symptoms and in control subjects.

Gastric dysrhythmias and normal gastric myoelectrical activity have been recorded in patients with functional dyspepsia. The aim of this study was to determine the reproducibility of gastric myoelectrical patterns and responses to a water load in patients with dysmotility-like functional dyspepsia and healthy control subjects. We studied 24 patients with dysmotility-like functional dyspepsia and 24 age-matched control subjects. Gastric myoelectrical activity was assessed using cutaneous electrodes to record electrogastrograms (EGGs) before and after the subjects ingested water until full. The EGGs with water load tests were repeated 1 week apart. The patients ingested significantly smaller volumes of water at both week 1 and 2 (358 +/- 26 mL and 349 +/- 30 mL) compared to control subjects (557 +/- 35 mL and 560 +/- 27 mL, p < 0.01). Gastric dysrhythmias were found in 4 of 24 (16.7%) control subjects at each visit and in 14 (58%) and 12 (50%) of the dyspeptic patients at week 1 and 2, respectively. Of 14 patients, 2 (14.3%) had gastric dysrhythmias at week 1 but had normal gastric rhythms at week 2. Thus, reproducibility was 100% in the control subjects and 91.7% in the patients. In conclusion, some variability in EGG pattern occurred, but gastric myoelectrical activity and responses to the water load test were generally consistent and reproducible in patients with dysmotility-like functional dyspepsia and in healthy control subjects.

Adolescent↗

Reproducibility of nurse-measured, exercise and ambulatory blood pressure and echocardiographic left ventricular mass in borderline hypertension.

OBJECTIVE: To compare the short-term reproducibility of four diagnostic tests: resting blood pressure, exercise blood pressure, non-invasive daytime ambulatory blood pressure and echocardiographic left ventricular mass. DESIGN: Blinded, prospective test-retest (reliability) study. SETTING: Hypertension research units in two teaching hospitals. PARTICIPANTS: Six normal volunteers and 22 patients with untreated borderline to mild hypertension, mean age 44 years. MAIN OUTCOME MEASURES: The intraclass correlation coefficient (RI) and standard deviation of the difference (SDD) between visits. MAIN RESULTS: The mean blood pressures and left ventricular mass did not differ between visits. Concordance between visits reached RI = 0.86 systolic/0.66 diastolic for ambulatory blood pressure and RI = 0.85 systolic/0.64 diastolic for nurse-measured random-zero sphygmomanometer resting blood pressure. The respective variabilities were SDD = 9/8 and 8/8 mmHg. Submaximal exercise systolic blood pressure (SBP) and echo left ventricular mass showed excellent reliability. Echo left ventricular mass and resting SBP or ambulatory SBP were significantly more reproducible than resting diastolic blood pressure (DBP) or ambulatory DBP. CONCLUSIONS: Despite averaging many readings within each day, clinically important between-visit variations in ambulatory blood pressure remained. The between-visit variability of daytime ambulatory blood pressure was similar to that of resting blood pressure when carefully measured by a research nurse. The echo left ventricular mass appears to be more reproducible over the short term than the current diagnostic standard for hypertension, the resting DBP.

Adult↗

Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study. Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation.

OBJECTIVE: To assess whether modifications in the nighttime blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension. METHODS: The analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular hypertrophy involved in the SAMPLE study. For each patient, ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index were performed at the end of a 4-week wash-out pretreatment period, after 3 and 12 months of treatment with lisinopril or with lisinopril plus hydrochlorothiazide and after a final 4-week placebo period. For each ambulatory blood pressure monitoring the 24 h average, daytime average (0600-2400 h), night-time average (2400-0600 h) and day-night difference was computed. The percentages of dipper and non-dipper patients (i.e. the patients with night blood pressure falls greater and less than 10% of the daytime average, respectively) were also computed. RESULTS: The reproducibility of the day-night difference was low, both for comparison of the pretreatment and final placebo periods (n = 170) and for comparison of the third and the 12th month of treatment (n = 180). The reproducibility of the dipper-non-dipper dichotomy was also low, 35-40% of patients becoming non-dippers if they were dippers and vice versa, both with and without treatment The changes in left ventricular mass index after 12 months of treatment were significantly (P<0.01) related to the changes in 24 h, daytime and night-time blood pressure (r always > 0.33), but this was not the case for the treatment-induced modification of the day-night difference (r= -0.03 and -0.008 for systolic and diastolic blood pressures, respectively). CONCLUSIONS: Our results show that day-night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time. It also provides the first prospective evidence that treatment-induced changes in day-night blood pressure difference are not related to treatment-induced regression of left ventricular mass index, thus having a limited clinical significance.

Adult↗

Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis.

OBJECTIVE: The aim of this study was to determine the reproducibility of pulse wave velocity (PWV) and augmentation index (AIx) measured using pulse wave analysis (PWA), prior to its use in large-scale clinical trials. METHODS: Arterial pressure waveforms were recorded and analysed using an established technique (Sphygmocor). Subjects with and without a range of recognized cardiovascular risk factors were studied to provide a wide range of values. Measurements were made after a brief introduction to the technique in a clinical setting. Two observers recorded aortic and brachial PWV in 24 subjects, each on two occasions, in a random order. In a separate study, two different observers used PWA to determine AIx in 33 subjects, each on two occasions, in a random order. Data were analysed using Bland-Altman plots and presented as mean +/- SD. RESULTS: Brachial PWV was 8.65+/-1.58 m/s (range 6.16-10.95 m/s) and aortic PWV was 8.15+/-3.01 m/s (5.01-17.97 m/s). Within-observer variability was 0.14+/-0.82 m/s for brachial PWV and 0.07+/-1.17 m/s for aortic PWV. Corresponding between-observer values were -0.44+/-1.09 m/s and -0.30+/-1.25 m/s. AIx ranged from -15.0 to +45.0%, with a group mean of +19.6+/-12.0%. The within-observer difference was 0.49+/-5.37% and between-observer difference 0.23+/-3.80%. CONCLUSION: PWA is a simple and reproducible technique with which to measure PWV and AIx. Reproducibility accords with that reported by other workers using different methodologies. PWA may, therefore, be suitable for large-scale population and intervention studies investigating the clinical relevance of vascular stiffness.

Adult↗

Clinic, home and ambulatory pulse pressure: comparison and reproducibility.

OBJECTIVE: Recent evidence suggests that pulse pressure (PP) is an independent predictor of cardiovascular risk. The objective of this study was to compare mean values and reproducibility of PP obtained in the clinic (CPP), at home (HPP) and with ambulatory monitoring (APP) and to evaluate potential implications for trials aiming to assess drug effects on PP. METHODS: A total of 393 hypertensive subjects [mean age 51.5 +/- 11.5 (SD) years, 59% men, 35% treated] measured CPP (two visits), HPP (6 days) and APP (24 h). The reproducibility of PP was assessed using the SD of differences (SDD) between measurements in 133 untreated subjects who had repeated CPP (five visits), HPP (6 days) and APP measurements (two occasions). RESULTS: There was no difference between mean CPP (51.0 +/- 13.3 mmHg) and HPP (50.2 +/- 11.0) whereas APP (48.8 +/- 8.4) was lower than both CPP [mean difference 2.3 +/- 10.3 mmHg; 95% confidence interval (CI), 1.2, 3.3; P < 0.01] and HPP (1.5 +/- 7.8; 95% CI, 0.7, 2.3; P < 0.01). The SDD between repeated measurements was about 10 mmHg for CPP (one visit), 5.2 mmHg for HPP (2 days) and 4 mmHg for APP (24-h). For a parallel comparative trial aiming to detect a difference of 3 mmHg PP in the effect of two drugs, 415 subjects would be required when using CPP, compared to 127 using HPP and 63 using APP. CONCLUSIONS: These data suggest that although differences among mean values of CPP, HPP and APP are small, differences in their reproducibility are important and should be taken into account in the design of trials assessing drug effects on PP.

Adult↗

Accuracy and reproducibility of 12-h esophageal pH monitoring.

Seventy-five consecutive 24-h intraesophageal pH recordings performed according to the methods of Jolley et al. were evaluated. Total scores and the mean duration of sleep reflux (ZMD) were calculated for the first and the last 12 h, respectively, and compared to each other, as well as to the full 24-h recording. The accuracy of the first and last 12 h in predicting whether the 24-h study was abnormal was 85% and 87%, respectively. The accuracy in predicting whether the ZMD for the 24-h study was abnormal was 73% and 83%, respectively, with an overall 39% false-negative rate. The 12-h study reproducibility was 72% for the total score and 56% for the ZMD. Since the original standards were determined from 18- to 24-h recordings, the test was restandardized based on 12-h recordings from patients with normal 24-h studies. Restandardization did not improve the accuracy or reproducibility. The high false-negative rate for the ZMD and the poor reproducibility cast serious doubt on the utility of 12-h pH recordings, especially in patients with respiratory symptoms.

Child↗

Reproducibility of preventable death judgments and problem identification in 60 consecutive road trauma fatalities in Victoria, Australia. Consultative Committee on Road Traffic Fatalities in Victoria.

BACKGROUND: Since 1992, the Consultative Committee on Road Traffic Fatalities in Victoria has identified problems in the management of traffic fatalities. Its two evaluative committees have additionally assessed the potential preventability of death. Previous studies have shown only poor to fair reproducibility of death judgments. METHODS: Problems in the management of 60 consecutive road traffic fatalities and the potential preventability of death were independently evaluated by the two committees. Inter-rater and inter-committee concordance were analyzed using the kappa statistic. RESULTS: Reproducibility was high. Inter-committee agreement on nonpreventable, potentially preventable, and preventable death judgments was high (kappa = 0.73, 95% confidence interval = 0.57-0.89). Agreement within the two evaluative committees was also high (average weighted kappa = 0.73 and 0.74). There was good agreement between committees on problems identified, including those contributing to death. CONCLUSION: The high kappa concordance on preventable death judgments and the agreement on problem identification supports the reproducibility of the methodology used.

Accidents, Traffic↗

Stability and reproducibility of brachial artery flow-mediated dilation.

PURPOSE: Brachial artery flow-mediated dilation (BAFMD) is a noninvasive technique, which has been suggested as a potential means of identifying patients with early atherosclerosis and therefore has enormous clinical appeal. Despite this, the stability and reproducibility of this technique are not yet clear. Therefore, the purpose of this study was to establish the stability and reproducibility of BAFMD after 5 min of forearm occlusion and to produce power calculations to aid in clinical trial design. METHODS: Twenty-six healthy volunteers underwent high-resolution ultrasonographic brachial artery assessments before, during, and after 5 min of forearm occlusion. The study design involved three scans on 2 d, performed by two ultrasonographers and analyzed by two readers. All subjects were tested between 7 and 11 a.m. after refraining from food and exercise. The nondominant arms were scanned, in longitudinal view, approximately 4 cm proximal to the olecranon process, in the anterior/medial plane. Blood draws were performed on each visit. The SAS MIXED restricted maximum likelihood (REML) procedure for an unbalanced design was used to calculate variance components and provide power calculations. RESULTS: Average baseline artery diameter for all studies was 3.48 +/- 0.53 mm. This increased to 3.71 +/- 0.57 mm (6.58 +/- 4.15%) at peak dilation. Intraclass correlation coefficients (ICCC) for days, testers, and readers were 0.92, 0.94, and 0.90, respectively. To detect a difference in vasoreactivity of 60% (two-tailed), e.g., 5% vasodilation versus 8% vasodilation, at 90% power, 23 and 10 subjects would be required for cross-sectional and pre-post designs, respectively. CONCLUSIONS: These data indicate adequate stability and reproducibility of the BAFMD technique under controlled conditions. Additionally, BAFMD appears useful to differentiate between groups, although its prognostic value for the examination of individuals is unclear.

Adult↗

Validity and reproducibility of a physical activity questionnaire in women.

PURPOSE: To determine the validity and reproducibility of a self-administered physical activity questionnaire that assesses the frequency, intensity, and duration of recreational, household, and occupational activity in women. METHODS: The questionnaire was administered by mail twice to 131 participants 1 yr apart. During this interval, participants completed four 1-wk activity logs corresponding to different seasons throughout the year. RESULTS: The intraclass correlation coefficients used to measure reproducibility were 0.82 for total activity, 0.79 for moderate activity, 0.86 for vigorous activity, 0.80 for recreational activity, and 0.73 for household activity. The distribution of activity scores was similar between the questionnaires and the average of the four logs, indicating the participants' ability to incorporate seasonal variation into their recall on a questionnaire. The correlations between the questionnaire-based activity scores and log-based activity scores, indicating validity, were 0.26 for total activity, 0.15 for moderate activity, and 0.52 for vigorous activity. Women younger than age 50 tended to have higher validity scores than women aged 50 yr and older (r = 0.31 vs r = 0.19, respectively, for total activity). CONCLUSION: These data indicate that this physical activity questionnaire is reproducible and provides a useful measure of current activity, particularly vigorous activity, over a 1-yr period.

Adult↗