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Reproducibility of a symptom response to omeprazole therapy in functional dyspepsia evaluated by a random-starting-day trial design.

BACKGROUND: Satisfactory treatment options for functional dyspepsia are lacking. Single subject trial designs may identify subgroups of patients with a uniform response to therapy. AIM: To test reproducibility of response in a new random-starting-day trial design developed to identify acid-related symptoms in functional dyspepsia. METHODS: One hundred and nineteen patients with functional dyspepsia completed a 12-day, double-blind random-starting-day trial with an initial placebo run-in followed by switch to omeprazole on a randomized and blinded day (between days 5 and 9) with active treatment continuing for the rest of the trial. Response was defined as a sustained > or =50% reduction of a daily symptom-score within 3 days of active treatment. Fifty-nine patients repeated the random-starting-day trial at relapse of symptoms. RESULTS: After exclusion of placebo responders, 14% (15 of 106) were classified as responders in the first and 20% (10 of 50) in the subsequent random-starting-day trial series. Sixty-eight per cent (40 of 59) of the patients reproduced their initial response with a chance-corrected agreement of 0.29. Comparing response patterns using different symptom rating-scales showed good correlation (kappa 0.60). CONCLUSION: Reproducibility of response in a random-starting-day trial was imperfect, mainly because of the low response rates and strict response criteria. Lack of symptom stability impairs the value of the random-starting-day trial and only patients with frequent and stable symptoms should be evaluated in this design.

Anti-Ulcer Agents↗

Comparison and reproducibility of transthoracic bioimpedance and dual beam Doppler ultrasound measurement of cardiac function in healthy volunteers.

1. We compared the ease of use and reproducibility of two noninvasive methods, transthoracic electrical bioimpedance (TEB) (BoMed NCCOM3-R7) and non-imaging dual beam Doppler ultrasound (Quantascope--Vital Science), in cardiac output (CO) and stroke volume (SV) measurement in healthy volunteers at rest and during physiological stress, both short term and from day to day. 2. The TEB method was easier to use and not dependent on the operator. The TEB method was more reproducible both in the short term and from day to day. Both devices were able to detect CO and SV changes under physiological stress, but were less reproducible day to day during exercise. 3. At supine rest, the within subject coefficient of variation between time point for TEB was 4.6% for CO and 6.1% for SV, and 7.9% for CO and 7.4% for SV with Doppler. 4. The results from each device showed a linear correlation coefficient (r) of 0.69 for CO (P less than 0.0005) and 0.64 for SV (P less than 0.0005). The correlation coefficient improved to 0.76 (P less than 0.0005) when only changes in CO and SV were considered. There was no systematic difference in the changes detected by the two methods, but the individual variation was wide.

Cardiography, Impedance↗

Feasibility and reproducibility of the [3H]-thymidine labelling index in breast cancer. The SICCAB Group for Quality Control of Cell Kinetic Determination.

For several malignancies, autoradiographic evaluation of the S phase cell fraction by means of [3H]-thymidine ([3H]dT) has proved a valid prognostic tool which should be included in a 'risk factor profile system' to estimate prognosis in individual patients. However, its clinical implementation requires a methodological standardization, a high feasibility and an assessment of the reproducibility of results, within and between different laboratories. The recent availability of a kit for in vitro incubation with [3H]dT and histological fixation of solid tumour specimens has contributed to the methodological simplification and standardization of the technical procedure, increasing its feasibility in several institutions. For breast cancer, preliminary results from a quality control study promoted by the Italian Society of Basic and Applied Cell Kinetics (SICCAB) showed a high inter-observer reproducibility within (r = 0.96) and between different laboratories (r = 0.93). Moreover, on a series of 20 autoradiographic samples sent to 15 different institutions, only 2% of tumours shifted from one of the cell kinetic subgroups, defined using the median [3H]dT labelling index (LI) of 2.8% as a cutoff, to the other. In addition, a marked consistency of results was observed among the different Italian institutions involved in cell kinetic studies on breast cancers, both in terms of median [3H]dT LI values and basic correlations. Periodic assessment of the reproducibility of [3H]dT LI evaluation among different laboratories is needed, especially for institutions involved in multicentre clinical protocols based on cell kinetic characteristics.

Breast Neoplasms↗

Reproducibility of 24-hour serum growth hormone profiles in man.

OBJECTIVE: To study the reproducibility of 24-h serum growth hormone (GH) concentration profiles in adults. DESIGN: 24-h serum GH concentrations were constructed by drawing blood samples at 20-min intervals. Four study occasions over a period of 1 year were chosen to assess the reproducibility. SUBJECTS: Six healthy adult male volunteers of normal height and weight and aged between 20 and 22 years. MEASURES: The resulting GH data arrays were analysed by Fourier transformation. Between and within individual variations were calculated and expressed in terms of coefficients of variation and data plotted to show variations between groups and individuals. RESULTS: The frequency component of GH secretion occurred with a dominant periodicity of between 160 and 240 min. Precise estimates of spectral power (strength of oscillatory activity) and period were obtained for group data, but such estimates cannot be inferred from a single profile. There was no significant difference in 24-h mean serum GH concentration over the year of study: occasion 1 (February) mean 2.0 mU/l (SD 0.5); occasion 2 (March) mean 3.7 mU/l (SD 2.8); occasion 3 (July) mean 2.7 mU/l (SD 1.4); occasion 4 (February) 2.5 mU/l (SD 1.5) (mean within individual coefficient of variation 35%, range 9-58). The concentrations of factors known to influence GH synthesis and secretion, insulin-like growth factor I, thyroxine, testosterone and oestradiol, varied little over the year of study. CONCLUSIONS: These data demonstrate that group data are reproducible in terms of oscillatory activity and the amount of GH secreted and that 24-h GH profiles should be used predominantly for analysing group data. The variability between individual profiles limits their value in the investigation of children with growth failure and suspected GH insufficiency.

Adult↗

The reproducibility and comparability of tests of the peripheral chemoreflex: comparing the transient hypoxic ventilatory drive test and the single-breath carbon dioxide response test in healthy subjects.

Both the transient hypoxic ventilatory drive test and the single-breath carbon dioxide (CO2) response test have been used to assess peripheral chemoreflex sensitivity. We tested their comparability in 14 healthy adults (10 men, aged 31-73 years, mean 55.4 years). The within-subject reproducibility of both tests was also assessed (n = 7 for each). The mean transient hypoxic ventilatory response was 0.287 +/- 0.0591 min-1 (%Sao2)-1 (mean +/- SEM, range 0.018- 0.718) and single-breath CO2 response was 0.276 +/- 0.0411 min-1T-1 (range 0.081-0.501). Both tests were reproducible with a mean coefficient of variation of 20.1% and 17.7%, respectively. There was, however, no significant correlation between the results of the transient hypoxic and single-breath CO2 tests when data were compared by linear regression analysis (r = 0.23, P = 0.43), suggesting that separate pathways of the peripheral chemoreflex existed for hypoxia and hypercapnia, respectively, and that these tests were specific for each. The authors conclude that these tests are reproducible but need to be used in combination for an adequate assessment of the peripheral chemoreflex.

Adult↗

Peripheral T-cell lymphomas: an evaluation of reproducibility of the updated Kiel classification.

Haematoxylin and eosin, and Giemsa stained sections from 100 peripheral T-cell lymphomas were examined blind on two occasions by four experienced haematopathologists in order to evaluate the inter- and intra-observer reproducibility of the updated Kiel classification for these malignancies. In all cases, the T-cell phenotype had been established previously in frozen section using a panel of monoclonal antibodies. Analysis by kappa statistics showed poor reproducibility, both overall and for most subtypes, with the exception of large cell anaplastic lymphoma. The distinction between low- and high-grade lymphomas was also unsatisfactory. These results indicate the need for improved precision in the definition of histological categories of peripheral T-cell lymphoma. The reproducibility of the update Kiel classification for peripheral T-cell lymphomas in its present form is inadequate.

Humans↗

Stereological estimate of nuclear volume in endometrial adenocarcinoma of endometrioid type: reproducibility and intra-tumour variation.

Stereological volume weighted mean nuclear volume estimate (Vv) is reported to be highly reproducible and to provide excellent prognostic information for some tumours. The aim of the present study was to investigate the reproducibility and the intra-tumour variation of nuclear Vv and compare it with a morphometric nuclear estimate, i.e. the mean shortest nuclear axis, and with conventional histopathological parameters used in the grading of endometrial adenocarcinomas. Sixty-three endometrioid adenocarcinomas were included in the study. Both Vv and mean shortest nuclear axis showed an acceptable reproducibility and the correlation between them was moderate (Spearman test; rs = 0.8). One-third of the tumours showed a marked intra-tumour variation. A considerable discrepancy between Vv and/or mean shortest nuclear axis and nuclear and architectural grade was found.

Adenocarcinoma↗

Dysplastic naevus: histological criteria and their inter-observer reproducibility.

Forty melanocytic lesions were examined in a pilot study, which was followed by a final series of 100 consecutive melanocytic lesions, in order to evaluate the inter-observer reproducibility of the histological criteria proposed for the dysplastic naevus. The specimens were examined in a blind fashion by four observers. Analysis by kappa statistics showed poor reproducibility of nuclear features, while reproducibility of architectural features was acceptable, improving in the final series. Consequently, we cannot apply the combined criteria of cytological and architectural features with any confidence in the diagnosis of dysplastic naevus, and, until further studies have documented that architectural criteria alone will suffice in the diagnosis of dysplastic naevus, we, as pathologists, shall avoid this term.

Biopsy↗

Estimation of the repeatability and reproducibility of three diagnostic tests for infectious salmon anaemia virus.

Reverse transcriptase polymerase chain reaction (RT-PCR), virus isolation (VI) and indirect fluorescent antibody tests (IFAT) are three assays currently used by the salmon industry to identify fish infected with infectious salmon anaemia virus (ISAV). However, no data are available on the repeatability (within-laboratory consistency) and reproducibility (between-laboratory consistency) of these assays and very limited information is available on the effect of freezing samples on test results. In order to evaluate these assays, five laboratories participated in a blinded study of 400 kidney samples representing four populations of farmed Atlantic salmon with different prevalence of ISAV. Each laboratory used its own testing protocols. Repeatability and reproducibility were evaluated using kappa as the measure of agreement. The effect of freezing was evaluated using the McNemar test. Freezing did not affect VI but improved the sensitivity of RT-PCR. The repeatability and reproducibility of VI was almost perfect. There was a substantial difference in repeatability of RT-PCR among the three laboratories with kappa ranging from 0.5 to 0.96. The repeatability for RT-PCR was generally low. The repeatability of IFAT was moderate when the results were analysed using 1+ and above as a positive result. The results of the study show the need to standardize the protocol and interpretation of RT-PCR.

Animals↗

Validation and reproducibility of a semi-quantitative Food Frequency Questionnaire for use in elderly Swiss women.

OBJECTIVE: The principal aim of this study was to develop a Swiss Food Frequency Questionnaire (FFQ) for the elderly population for use in a study to investigate the influence of nutritional factors on bone health. The secondary aim was to assess its validity and both short-term and long-term reproducibility. DESIGN: A 4-day weighed record (4 d WR) was applied to 51 randomly selected women of a mean age of 80.3 years. Subsequently, a detailed FFQ was developed, cross-validated against a further 44 4-d WR, and the short- (1 month, n = 15) and long-term (12 months, n = 14) reproducibility examined. SETTING: French speaking part of Switzerland. SUBJECTS: The subjects were randomly selected women recruited from the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture cohort study. RESULTS: Mean energy intakes by 4-d WR and FFQ showed no significant difference [1564.9 kcal (SD 351.1); 1641.3 kcal (SD 523.2) respectively]. Mean crude nutrient intakes were also similar (with nonsignifcant P-values examining the differences in intake) and ranged from 0.13 (potassium) to 0.48 (magnesium). Similar results were found in the reproducibility studies. CONCLUSION: These findings provide evidence that this FFQ adequately estimates nutrient intakes and can be used to rank individuals within distributions of intake in specific populations.

Aged↗

Reproducibility of a method for analysis of morphological changes in perioral soft tissue in children using video cameras.

The purpose of the present study was to determine the appropriate reference facial expression and to examine the reproducibility of our system using two commercially available video cameras in consideration of functional diagnosis of perioral muscles. The following items were investigated: 1) influence of forward and backward movements and the experiment sequence from measurement to analysis, 2) usefulness of head fixation by a restraining device during video recording for evaluation of morphological changes in facial expression, 3) conditions for establishment of reference points for determination of movements of perioral soft tissue, and 4) reproducibility of perioral soft tissue movements as assessed by changes in landmarks. The results of this study showed that accurate static and dynamic evaluation of perioral soft tissue is possible by using our method of video recording with the subject's head restrained and our method of analysis. The results also showed that centric occlusion of the most appropriate reference facial expression as for measurement of perioral soft tissue movements and that protrusion of the lips and lateral extension of the angel of the mouth are facial expressions with high degrees of reproducibility.

Child, Preschool↗

Reproducibility of gastric tone, compliance and gastric accommodation assessed with barostat in conscious dogs.

The reproducibility of barostat measurements was unclear. In this study, the intraday and interday reproducibility of barostat measurements of gastric tone, compliance and gastric accommodation were assessed in a canine model. A series of experiments were performed using a barostat system in 11 surgically prepared healthy dogs: (i) interday gastric tone and compliance: three sessions on three separate days; (ii) intraday gastric tone and compliance: two sessions on the same day separated by a 30-min interval; (iii) interday gastric accommodation: two sessions on two separate days, with each including a 30-min baseline and a 60-min postprandial period. The results were (i) interday gastric tone (81.2 +/- 7.5 mL vs 89.2 +/- 8.1 mL vs 86.2 +/- 13.6 mL, n = 11) and compliance (n = 8) were comparable; (ii) intraday gastric tone (87.9 +/- 17.2 mL vs 77.0 +/-14.8 mL, n = 8) and compliance (n = 8) was also similar, but with considerable individual variance; (iii) interday gastric accommodation was 320.8 +/-45.1 mL vs 287.9 +/- 31.2 mL, no significant difference (n = 8). Inter- and intraday gastric tone and compliance and interday gastric accommodation were relatively reproducible in most animals when tested under well-controlled conditions. However, considerable variations may occur in fasting gastric tone and compliance measurements in certain individuals and cautions should be given when interpreting related results.

Animals↗

Field validity, reproducibility and feasibility of diagnostic tests for visceral leishmaniasis in rural Nepal.

OBJECTIVES: To assess the field accuracy, reproducibility and feasibility of the formol gel test (FGT), the urine latex agglutination test (KAtex) and a rK39 antigen-based dipstick for the diagnosis of visceral leishmaniasis (VL) in rural Nepal. METHOD: Patients with clinical suspicion of VL were recruited at Rangeli District Hospital (DH), a 15-bed government hospital located in south-eastern Nepal. FGT, KAtex and rK39 dipstick tests were performed on site and later repeated at a reference kala-azar diagnostic laboratory to assess reproducibility. Diagnosis of VL was confirmed by either a positive bone marrow aspirate examination or a positive direct agglutination test (DAT titre > or = 1:3200) in patients who later responded to anti-leishmanial therapy. RESULTS: Of 155 patients initially recruited, 142 (85 with VL and 57 with another diagnosis) were included in the study. The sensitivity of the rK39 dipstick [89%; 95% confidence interval (CI): 81-94] was significantly higher than that of the KAtex (57%; 95% CI: 46-67) and the FGT (52%; 95% CI: 41-62). All three tests had a specificity of at least 90%. Agreement was higher for the rK39 dipstick (kappa = 0.87) than for the FGT (0.68) and the KAtex (0.43). All tests required < or = 20 min of actual work and < or = 40 min to obtain the results. CONCLUSION: The rK39 dipstick was easy to do, more accurate and reproducible than other rapid diagnostic tests for VL in a DH of rural Nepal. It should be integrated into the field diagnostic algorithm of VL in this region and mechanisms to secure its availability should be found.

Adult↗

Reproducibility of leukotriene D4 inhalation challenge in asthmatics. Effect of a novel leukotriene D4/E4-antagonist (SR 2640) on leukotriene D4-induced bronchoconstriction.

We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics.

Adult↗

Evaluation of a composite scoring system in conjunctival challenge with allergen: reproducibility and evolution during loratadine treatment.

The reproducibility of any challenge and its sensitivity to change during therapeutic interventions should always be examined before any drug trial is conducted. Conjunctival challenge has been widely used to assess objectively the efficacy of antiallergic treatments. A double-blind, placebo-controlled, crossover study was carried out in 26 patients allergic to grass pollen to test the reproducibility of a composite symptom score during placebo and control days, and to check the ability of loratadine to increase the provocative dose inducing a positive challenge. Conjunctival challenge was carried out with increasing concentrations of a standardized orchard grass pollen extract until a composite symptom score of 5 was reached. The provocative dose inducing a positive challenge was similar for the baseline (6.94 +/- 8.7 index of reactivity (IR)) and placebo days (20.0 +/- 32.5 IR) and was significantly increased (P < 0.01 and P < 0.001) when patients received loratadine (117.3 +/- 136.8 IR). This study shows that the composite score used was reproducible and sensitive to change, making it possible to use in drug trials.

Adult↗

Reproducibility of skin prick test results in epidemiologic studies: a comparison of two devices.

The reproducibility of skin prick tests under field conditions is essential for comparing prevalences between centers in epidemiologic multicenter studies. This study aimed to evaluate and compare the reproducibility of two widely used skin prick test devices: the Multi-Test and the ALK lancet. The subjects were 28 children, aged 6-14 years, with known sensitivities to Dermatophagoides pteronyssinus (D. pter.). Both devices were applied to each subject on two occasions, 1 week apart, by different, randomly assigned fieldworkers, using histamine, negative control, and the D. pter. allergen extract. For all three tested solutions, mean wheal sizes were larger for the Multi-Test than for the ALK lancet. The coefficient of variation for histamine was 21.8% for the Multi-Test and 17.3% for the ALK lancet. The coefficients of variation for the allergen D. pter. amounted to 47.4% for the Multi-Test and to 24.6% for the ALK lancet. The percentage of concordant test results was 92.6% for the Multi-Test and 100.0% for the ALK lancet for a cutoff point of wheal size equal to or greater than 1 mm. The results of this study suggest that the single ALK lancet performs slightly better than the Multi-Test device with respect to reproducibility under conditions of epidemiologic field studies.

Adolescent↗

Symposium: evaluating the reproducibility of pathological diagnosis using the 1997 Banff classification update.

The purpose of this symposium was to evaluate the reproducibility of a histological diagnosis in renal allograft nephropathy according to the Banff classification. Seven transplant nephrologists and pathologists independently diagnosed the same glass slide specimens from 10 cases (five cases of acute rejection and five cases of chronic allograft nephropathy). Their diagnoses were collated and analyzed for the reproducibility of histological diagnosis. Consequently, several issues that hinder diagnostic reproducibility were identified.

Biopsy↗

A comparison of RANZCR and Singapore-designed radiation oncology practice audit instruments: how does reproducibility affect future approaches to revalidation?

Physician competency assessment requires the use of validated methods and instruments. The Royal Australian and New Zealand College of Radiologists (RANZCR) developed a draft audit form to be evaluated as a competency assessment instrument for radiation oncologists (ROs) in Australasia. We evaluated the reliability of the RANZCR instrument as well as a separate The Cancer Institute (TCI) Singapore-designed instrument by having two ROs perform an independent chart review of 80 randomly selected patients seen at The Cancer Institute (TCI), Singapore. Both RANZCR and TCI Singapore instruments were used to score each chart. Inter- and intra-observer reliability for both audit instruments were compared using misclassification rates as the primary end-point. Overall, for inter-observer reproducibility, 2.3% of TCI Singapore items were misclassified compared to 22.3% of RANZCR items (P < 0.0001, 100.00% confidence that TCI instrument has less inter-observer misclassification). For intra-observer reproducibility, 2.4% of TCI Singapore items were misclassified compared to 13.6% of RANZCR items (P < 0.0001, 100.00% confidence that TCI instrument has less intra-observer misclassification). The proposed RANZCR RO revalidation audit instrument requires further refinement to improve validity. Several items require modification or removal because of lack of reliability, whereas inclusion of other important and reproducible items can be incorporated as demonstrated by the TCI Singapore instrument. The TCI Singapore instrument also has the advantage of incorporating a simple scoring system and criticality index to allow discrimination between ROs and comparisons against future College standards.

Certification↗