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Repeatability and reproducibility of retention data and band profiles on reversed-phase liquid chromatography columns. III. Results obtained with Kromasil C18 columns.

The reproducibility of the retention data and the band profiles was investigated with Kromasil C18 columns (silica-based monomeric type reversed-phase packing material). High precision data were obtained and statistically compared among five columns from the same batch (column-to-column reproducibility) and six columns, one from each of six different batches (batch-to-batch reproducibility). These data were acquired under five different sets of chromatographic conditions, for a group of 30 neutral, acidic and basic compounds selected as probes following an experimental protocol previously described. Data characterizing the retention time, the retention factor, the separation factor, the column efficiency and the peak asymmetry for the different probe compounds are reported. Factors describing the silica surface interaction with the selected probe compounds, such as the hydrophobic interaction selectivity, the steric selectivity, and the separation factors of basic compounds at different pH values were also determined. The influence of the underlying silica on these data and correlations between the chromatographic and physico-chemical properties of the different batches are discussed.

Chromatography, Liquid↗

Effect of residual noise level on reproducibility of the signal-averaged ECG.

Late potentials are detected at various noise levels in clinical studies. The aim of this study was to assess the effect of residual noise level on the reproducibility of the signal-averaged electrocardiogram (ECG). Two consecutive raw 15-minute ECG from each of 188 patients with coronary artery disease were digitized and stored on optical discs. Each raw ECG was analyzed by two signal-averaging procedures to noise level 0.2 microV or 0.4 microV. Standard time-domain parameters were measured: QRS duration (SA-QRS), late potential (LP) duration, and root-mean-square voltage of the terminal 40 ms of the filtered QRS (RMS40). The SA-QRS was prolonged by 12 +/- 14 ms by the reduction in noise level from 0.4 microV to 0.2 microV, LP duration was prolonged by 10 +/- 10 ms, and RMS40 was reduced by 19 +/- 22 microV. The temporal variation of the measured SA-QRS from ECG1 to ECG2 was significantly lower at noise level 0.2 microV (9 +/- 13 ms) than at noise level 0.4 microV (13 +/- 14 ms) (P < .001). The LP duration was also more stable at noise level 0.2 microV than at noise level 0.4 microV (0.5 +/- 11 ms vs 2 +/- 13 ms, P < .05). The presence of any two of three abnormal parameters (SA-QRS > 120 ms, RMS40 < 25 microV, LP duration > 40 ms) was used as the criterion for the presence of LPs. At noise level 0.4 microV, the proportion of patients with diagnosed LPs in ECG1 was 25% and at noise level 0.2 microV it was 62%. At noise level 0.4 microV, 20% were reclassified from LP-negative in ECG1 to LP-positive in ECG2, and 7% were reclassified from LP-positive in ECG1 to LP-negative in ECG2. At noise level 0.2 microV, 20% were reclassified from LP-negative in ECG1 to LP-positive in ECG2, and 9% were reclassified from LP-positive in ECG1 to LP-negative in ECG2. It was concluded that (1) the diagnosis of LPs is significantly dependent on the extent of noise reduction by signal averaging: and (2) the numerical reproducibility of signal-averaged QRS duration and LP duration is lower at noise level 0.4 microV then at noise level 0.2 microV; and the diagnostic reproducibility of LPs is similar at both noise levels.

Aged↗

Autoreactivity, backstimulation and reproducibility in a helper T lymphocyte precursor assay.

Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis (LDA) have a predictive value for alloreactivity in allogeneic bone marrow transplantation. Methodological problems in LDA include autoreactivity in the responder or stimulator cell populations and interleukin 2 (IL-2) production by the stimulator cells as a response to the responder cells (backstimulation). The extent and impact of these aspects for IL-2 production and HTLp frequency determination were studied by autologous and allogeneic mixed lymphocyte reactions with healthy volunteers and HTLp determinations from bone marrow transplantation donor/recipient pairs. We found that autoreactivity occurred in the unirradiated cells with a reproducible inter-individual variation. The immunogenicity of the stimulator cells was preserved after gamma irradiation with 50 Gy and the risks of autoreactivity and backstimulation were limited. Higher doses of irradiation decreased the immunogenicity. Immune reactions to antigens present in the serum supplement of the culture medium were seen with foetal calf serum and to a lesser extent with pooled human sera. This could be avoided by the use of autologous serum. We were unable to ensure satisfactory culture conditions in serum-free medium. The reproducibility of the HTLp frequency determinations was tested for intra- and inter-assay variation. The coefficients of variation were estimated as 24% and 35%, respectively. This was acceptable considering the range of the HTLp frequencies (1:10(2) to 1:10(7)). The influence of the extent of autoreactivity of the bone marrow donors was investigated in 28 HLA-identical sibling transplantations. We found no correlation between the autoreactivity of the donors and the HTLp frequencies. The extent of autoreactivity of the donor did not correlate with the clinical outcome in terms of acute graft-versus-host disease, treatment-related mortality, risk of relapse and overall survival. In spite of methodological difficulties and interference from autoreactivity and backstimulation, reproducible quantification of clinically significant alloreactivity can be attained.

Autoimmunity↗

The reproducibility of power spectrum analysis of heart rate variability before and after a standardized meal.

We tested the reproducibility of the heart rate variability (HRV) measurements before and after a standardized meal. Heart rate recordings were obtained in 14 healthy subjects tested in a reclining position before and after a standardized meal on two separated occasions, apart by a 1-2-week interval. We measured three components of HRV: sympathetic activity (SYMP), parasympathetic activity (PSYMP) and the ratio of SYMP/PSYMP under controlled breathing and noncontrolled breathing conditions. We observed that all components were reproducible during noncontrolled breathing condition, whereas only PSYMP was reproducible during controlled breathing condition. Our results thus indicate that HRV measurements could be a useful, noninvasive and nonexpensive method to provide SYMP and SYMP/PSYMP in feeding behavior studies when measured under noncontrolled breathing conditions. Nonetheless, using a controlled breathing condition may be relevant when assessing the effect of various interventions or drugs on parasympathetic activity.

Adult↗

Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma.

We evaluated the interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma (FTC). Forty-one anonymous FTC pathology slides were independently reviewed by 5 pathologists, and 31 of them were also evaluated twice by the same pathologist. A final consensus diagnosis (FCD) was made at the end of the study. Interobserver and intraobserver agreement was determined as the kappa statistic for qualitative data and intraclass correlation coefficient for quantitative data. The agreement between the 5 observers' initial diagnosis and the FCD was 0.69, 0.41, 0.35, 0.28 and 0.11, respectively, strongly suggesting a leadership phenomenon. The FCD classified 30 cases as malignant, including 24 cases diagnosed as FTC. There was unanimous agreement about 13 of the 24 FTCs. Diagnostic reproducibility was found to be acceptable for the nonminimally invasive FTC. Diagnostic discrepancies occurred in 57% of the seven cases classified as minimally invasive FTC by the FCD. FCD excluded malignancy in 11 cases including 6 atypical adenomas. Interobserver and intraobserver agreement for FTC diagnosis was 0.23 (standard error [SE], 0.04) and 0.68, respectively. Interobserver and intraobserver agreement for the presence of vascular invasion was 0.20 (SE, 0.04) and 0.51, respectively, contrasting with a moderate to substantial level of agreement when considering the number of vascular invasion. Interobserver and intraobserver agreement for nucleus optical clearing were slight and moderate, respectively. The importance of the study is the confirmation that diagnostic reproducibility of minimally invasive FTC is low and that this has clinical implications, and also implications for the design of studies into the treatment and outcome of FTC.

Adenocarcinoma, Follicular↗

Atypical immature metaplastic-like proliferations of the cervix: diagnostic reproducibility and viral (HPV) correlates.

Although some immature squamous lesions (papillary immature metaplasias) of the cervix have been described and associated with human papillomaviruses (HPV), nonpapillary atypical immature squamous proliferations (AISPs) are a poorly defined entity and range from atypical reactive metaplasias to squamous intraepithelial lesions resembling immature metaplasia. This study examined the diagnostic reproducibility of AISPs and their relationship to HPV nucleic acids. Forty-four diagnostically problematic AISPs were studied. Based on nuclear density (crowding), chromasia, variation (anisokaryosis) in nuclear size, and surface cytoplasmic maturation, cases were independently scored by 2 observers as (1) probably reactive (Rx), (2) not otherwise specified (NOS), and (3) squamous intraepithelial lesion (SIL). Extracted archival DNA was scored for HPV by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Interobserver reproducibility (kappa statistic) and HPV correlates (chi square) were computed. Approximately one third of cases were classified in each category by the observers. Interobserver reproducibility was excellent (0.80), poor (0.23), and fair to good (0.41) for a diagnosis of Rx, NOS, and SIL, respectively. Differences in HPV DNA positivity between Rx and SIL were significant for both observers (5.8% to 6.7% v 38.4% to 50.0%, respectively); however, differences between NOS and SIL (30.7% to 42.8% v 38.4% to 50.0%) were not, even when cases were limited to those in which both observers agreed (28.6% v 37.5%). By light microscopy, AISPs exceeding the threshold for presumed reactive changes (NOS or SIL) are a morphologically heterogeneous group that defy precise classification. Furthermore, their histopathologic appearance, even when there is diagnostic agreement, does not consistently correlate with their HPV status. The laboratory management of AISPs should take into account the uncertainty of this diagnosis.

Cell Division↗

Reproducibility of pressure-flow variables in patients with symptomatic benign prostatic hyperplasia.

OBJECTIVES: To study the reproducibility of pressure-flow studies in patients with symptomatic benign prostatic hyperplasia and to investigate if the reproducibility is influenced by the method of intravesical pressure measurement, that is, transurethral catheterization versus suprapubic puncture. METHODS: The within-patient variation of maximum urinary flow rates and detrusor pressure at maximum flow was investigated in 25 patients in whom 2 (transurethral group) or 3 (suprapubic group) sequential voidings during urodynamic investigation were analyzed. RESULTS: The within-patient variation of pressure-flow values was evaluated by the intraclass correlation coefficient, which was 0.71 for maximum urinary flow rate and 0.84 for detrusor pressure, suggesting a relatively high degree of reproducibility. However in 26% of the patients, the maximum flow rates changed by more than 3 mL/s or the detrusor pressure by more than 20 cm H2O during the repeated tests. There was no significant difference in the within-patient variation of pressure-flow values between the suprapubic group and the transurethral group. CONCLUSIONS: In larger clinical trials where the assessment of treatment effects between groups is desired, a single pressure-flow test is sufficient. In the individual patient, a single pressure-flow curve is of limited value due to a considerable within-patient variation of the test and, for these patients, multiple consecutive tests are recommended for diagnosis of intravesical obstruction and assessment of individual patient's response to treatment.

Aged↗

Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography.

OBJECTIVE: To evaluate the reproducibility of optical coherence tomograph (OCT) retinal nerve fiber layer (RNFL) measurements in normal and glaucomatous eyes by means of the commercially available OCT 2000 instrument (Humphrey Systems, Dublin, CA). DESIGN: Prospective instrument validation study. PARTICIPANTS: One eye each from 10 normal subjects and 10 glaucoma patients. METHODS: Twenty subjects underwent a total of eight scanning sessions during two independent visits. In each session, five circular scans centered on the optic nerve head were performed. The first two sessions were performed by two experienced technicians. Followed by a 30-minute break, a third and a fourth session was completed by the same technicians. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of quadrant and global RNFL measurements were calculated by use of a components of variance model. MAIN OUTCOME MEASURES: RNFL thickness. RESULTS: The coefficient of variation for the mean RNFL thickness was significantly smaller (P = 0.02) in normal eyes (6.9%) than in glaucoma eyes (11.8%). The estimated root mean squared error based on the statistical model using three scans per patient was 5.8 and 8.0 micrometer for normal and glaucoma eyes, respectively. A components of variance model showed most of the variance (79%) to be due to differences between patients. Only a modest contribution to variability was found for session (1%), visit (5%), and operator (2%). CONCLUSION: With the commercially available OCT, our results indicate that the RNFL measurements are reproducible for both normal and glaucomatous eyes.

Adult↗

Intraobserver and interobserver reproducibility in the evaluation of optic disc stereometric parameters by Heidelberg Retina Tomograph.

PURPOSE: To assess intraobserver and interobserver reproducibility of the measurement of stereometric parameters of the optic disc by means of the Heidelberg Retina Tomograph I (HRT). STUDY DESIGN: Observational study, with interobserver variability. PARTICIPANTS: Fifty-five volunteers (healthy subjects and patients with glaucoma). METHODS: HRT examination of the optic disc was repeated on 3 consecutive days on 1 eye of each of the 55 subjects. During each session, five single images were randomly acquired by two independent observers. One mean topography image (MTI), based on three single images, was then built at each session. For the intraobserver intraimage evaluation, the two observers traced their own contour line on one randomly chosen MTI. This procedure was repeated three times. For the intraobserver interimage and interobserver intra/interimage evaluations, the two observers traced their own contour line on the MTI of the first session, which was then automatically superimposed on the MTIs of the other two sessions. MAIN OUTCOME MEASURES: Reproducibility of the 12 stereometric parameters was calculated for each observer by means of the intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated by the scatter-plots of each test-retest difference versus their mean. The standard deviation of the mean test-retest score differences was used to describe the spread of score differences. RESULTS: The ICC ranged between 0.79 and 0.99 for intraobserver intraimage and between 0.56 and 1 for intraobserver interimage evaluation. The ICC ranged between 0.54 and 0.99 for interobserver intraimage and between 0.65 and 0.97 for the interobserver interimage evaluation. ICC was almost perfect to perfect for planimetric measures (0.81 < ICC < or = 1), substantial to almost perfect for volumetric and cup measures (0.61 < ICC < or = 0.99), and moderate to almost perfect for retinal nerve fiber layer related measures (0.41 < ICC < 0.99). The expected variability was low (95% confidence interval, < +/-9%). Interimage evaluation showed a higher variability than intraimage evaluation in both of interobserver (P = 0.012) and intraobserver evaluation (P = 0.028 and P = 0.031 for the two observers). CONCLUSIONS: Measurement of optic disc stereometric parameters by HRT is highly reproducible. However, the use of retinal nerve fiber layer-related parameters should be taken cautiously. The image acquisition-induced variability seems larger than the operator-induced variability.

Adult↗

Comparison of flap thickness reproducibility using microkeratomes with a second motor for advancement.

PURPOSE: To compare flap thickness and reproducibility of four different types of microkeratomes during LASIK. DESIGN: Retrospective, nonrandomized, comparative case series. PARTICIPANTS: Four hundred ninety consecutive eyes underwent LASIK and were evaluated by measuring the central flap thickness by subtractive pachymetry. METHODS: All flaps were created using the Bausch & Lomb (Miami, FL) Hansatome 180 head, the Alcon (Fort Worth, TX) Summit Krumeich Barraquer Microkeratome 160 head, the Moria (Antony, France) Carriazo Barraquer (CB) 130 head, or the Moria M2 110 head. RESULTS: The flap thickness measurements differed according to the microkeratome used and were 131+/-28 microm in 41 eyes (8.4%) with the Bausch & Lomb Hansatome 180 head, 162+/-21 microm in 127 eyes (25.9%) with the Alcon Summit Krumeich Barraquer Microkeratome (SKBM) 160 head, 157+/-40 microm in 65 eyes (13.3%) with the Moria CB 130 head, and 134+/-23 microm in 257 eyes (52.4%) with the Moria M2 110 head. The central flap thickness with the SKBM and Moria M2 was statistically significantly more reproducible than with the Moria CB (P< 0.0005). There is no correlation between flap thickness reproducibility and age, corneal thickness, or corneal keratometric values. However, considering all the microkeratomes, female gender had statistically significantly more variability than male gender (P<0.02). CONCLUSIONS: Based on these results, the greatest predictability of flap thickness was seen with the SKBM and Moria M2 microkeratomes, which both use a second motor for advancement. The greatest variability, noted with the Moria CB, was likely due to the manual translation feature and places further importance on the safety of the second motor and automation when performing LASIK.

Adult↗

Reproducibility of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase sequencing of plasma samples from heavily treated HIV-1-infected individuals.

The reproducibility of population-based human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT) sequencing was assessed using replicate aliquots of cryopreserved plasma samples obtained from seven heavily treated HIV-1-infected individuals. The sequence of each sample replicate was compared with the consensus sequence for that sample and 99.4% of 35128 amino acids were found to be concordant with the sample consensus. Partial discordances were present at 0.5% of positions and complete discordances were present at <0.1% of positions. To assess the reproducibility at detecting mutations (defined here as differences from the subtype B consensus sequence), the proportion of sequences having a mutation when at least two sequences from that sample had the same mutation were examined. There was a median of 13 protease and 18 RT mutations per sample for a total of 3126 mutations; 95% of these mutations were detected. However, sequencing of multiple clones from two samples demonstrated that those mutations present in a minority of clones were often not detected by population-based sequencing. These results suggest that HIV-1 protease and RT sequencing of circulating plasma virus is highly reproducible but that the sensitivity at detecting mutations may be low if those mutations are present as minor variants.

Anti-HIV Agents↗

How high can a correlation coefficient be? Effects of limited reproducibility of common cardiological measures.

In clinical studies the linear correlation coefficient is commonly used to quantify the strength of the association between two variables, such as height and weight: the value of r indicates whether the relationship is a strong one. However, actual clinical data includes an underlying physical variable plus an inevitable measurement error component that represents the reproducibility of the test used. If test reproducibility is poor, then even if the underlying physical variables are perfectly correlated, the actual observed correlation coefficient cannot be one but must be somewhat less. We present a method for calculating the reduction in correlation coefficient due to limited reproducibility, and discuss its implications with respect to experimental design and interpretation.

Echocardiography↗

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

BACKGROUND AND PURPOSE: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). MATERIALS AND METHODS: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). RESULTS: A decrease of TC to <95% was found in 3/60 simulations (5%) of pulmonary and 7/58 simulations (12%) of hepatic targets. In two of 22 pulmonary targets (9%) and in four of 21 hepatic targets (19%) a TC of <95% occurred in at least one fraction. At risk for a decreased TC <95% were pulmonary targets with increased breathing mobility and hepatic targets with a CTV exceeding 100 cm(3). CONCLUSIONS: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV >or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.

Adolescent↗

CT simulation in stereotactic brain radiotherapy--analysis of isocenter reproducibility with mask fixation.

BACKGROUND AND PURPOSE: CT verification and measurement of isocenter deviation using repeated mask fixation in linac-based stereotactic high dose radiotherapy of brain metastases were performed in this study. MATERIALS AND METHODS: For stereotactic radiotherapy of brain metastases a commercial head mask fixation device based on thermoplastic materials (BrainLAB) was used. A two-step planning-treatment procedure was performed. Immediately before treatment the patient was relocated in the mask and a verification CT scan of the radiopaque marked isocenter was performed and if necessary its position was corrected. The verification procedure is described in detail. Twenty-two CT verifications in 16 patients were analyzed. Deviations were measured separately for each direction. A 3D-deviation vector was calculated. Additionally the average amount of deviation in each of the three dimensions was calculated. RESULTS: The mean deviation and standard deviation (SD) of the isocenter was 0.4 mm (SD 1.5 mm) in the longitudinal direction, -0.1 mm (SD 1.8 mm) in the lateral direction and 0.1 mm (SD 1.2 mm) in the anterior-posterior direction. The mean three-dimensional distance (3D-vector) between the verified and the corrected isocenter was 2.4 mm (SD 1.3 mm). The average deviation (without consideration of direction) was 1.1 mm (SD 1.1 mm), 1.3 mm (SD 1.3 mm) and 0.8 mm (SD 0.9 mm) in the longitudinal, lateral and sagittal directions, respectively. No correlation was found between 3D-deviation and the distance of the isocenter from the reference plane nor between deviation and the position of metastases in the brain (central versus peripheral or between different lobes), or the date of treatment. CONCLUSION: Reproducibility of the isocenter using the presented mask fixation is in the range of positioning reproducibility reported for other non-invasive fixation devices for stereotactic brain treatment. Our results underline the importance of CT verification as a quality assurance method in stereotactic radiotherapy. Under the condition of a preceding CT verification the mask can be used for single dose stereotactic radiotherapy. For fractionated stereotactic irradiation of small target volumes we recommend repeated CT verifications to assure reproducibility.

Brain Neoplasms↗

Reproducibility of callosal effects of transcranial magnetic stimulation (TMS) with interhemispheric paired pulses.

Transcranial magnetic stimulation (TMS) of the motor cortex of one hemisphere (conditioning stimulus (CS)) inhibits EMG responses evoked in distal hand muscles by a later magnetic stimulus given at an appropriate interval, over the opposite hemisphere (test stimulus (TS)). This effect is commonly attributed to an inhibition produced at cortical level via a transcallosal route. The present study assessed the reproducibility of the transcallosal inhibition effects in different sessions in healthy subjects. Within- and between-subject variability, relating to interhemispheric differences was also evaluated. A magnetic CS on one hemisphere effectively inhibited EMG responses of the abductor digiti minimi stimulated by a TS delivered over the opposite hemisphere in a range of intervals centered at 12 ms. Even though group effects were reproduced in separate sessions, the high between- and within-subject variability yielded low test-retest correlations. This differentiation forces the definition of reproducibility (or repeatability), as the replication of the same mean curves of EMG reduction, and of reliability, as the between- or within-subject correlations between values of specific EMG measures.

Adult↗

Reproducibility of patch tests. A multicenter study of synchronous left-versus right-sided patch tests by the German Contact Dermatitis Research Group.

BACKGROUND: The efficiency and reproducibility of patch tests remain controversial. OBJECTIVE: Our purpose was to determine the efficiency and reproducibility of patch tests and to identify factors influencing these features. METHODS: We double-tested 1285 patients concomitantly with 10 standard allergens by manually filled test chambers. Additional information was obtained from all patients with a standardized protocol. RESULTS: Patch test efficiency was good (> or = 0.94) with all 10 allergens. In contrast, nonreproducibility of patch tests was strongly allergen dependent, ranging from 0.2 for nickel sulfate to 0.6 for formaldehyde. The likelihood of nonreproducible allergic reactions increased when more than four positive reactions were seen at the same time, and with another positive reaction located in close proximity to an allergic reaction. Sex and age of patients, atopy, dermatitis at distant sites, sleeping habits, and the time of allergen exposure (24 or 48 hours) did not affect the rate of nonreproducible results. CONCLUSION: To increase patch test reproducibility, specific preparations of patch test allergens need to be improved. Furthermore, amplification effects by synchronous neighboring positive reactions should be excluded.

Allergens↗

Cincinnati Prehospital Stroke Scale: reproducibility and validity.

STUDY OBJECTIVE: The Cincinnati Prehospital Stroke Scale (CPSS) is a 3-item scale based on a simplification of the National Institutes of Health (NIH) Stroke Scale. When performed by a physician, it has a high sensitivity and specificity in identifying patients with stroke who are candidates for thrombolysis. The objective of this study was to validate and verify the reproducibility of the CPSS when used by prehospital providers. METHODS: The CPSS was performed and scored by a physician certified in the use of the NIH Stroke Scale (gold standard). Simultaneously, a group of 4 paramedics and EMTs scored the same patient. RESULTS: A total of 860 scales were completed on a convenience sample of 171 patients from the emergency department and neurology inpatient service. Of these patients, 49 had a diagnosis of stroke or transient ischemic attack. High reproducibility was observed among prehospital providers for total score (intraclass correlation coefficient [rI],.89; 95% confidence interval [CI],.87 to.92) and for each scale item: arm weakness, speech, and facial droop (.91,.84, and.75, respectively). There was excellent intraclass correlation between the physician and the prehospital providers for total score (rI,.92; 95% CI,.89 to.93) and for the specific items of the scale (.91,.87, and.78, respectively). Observation by the physician of an abnormality in any 1 of the 3 stroke scale items had a sensitivity of 66% and specificity of 87% in identifying a stroke patient. The sensitivity was 88% for identification of patients with anterior circulation strokes. CONCLUSION: The CPSS has excellent reproducibility among prehospital personnel and physicians. It has good validity in identifying patients with stroke who are candidates for thrombolytic therapy, especially those with anterior circulation stroke.

Aged↗

Reproducibility and responsiveness of health status measures. Statistics and strategies for evaluation.

Before being introduced to wide use, health status instruments should be evaluated for reliability and validity. Increasingly, they are also tested for responsiveness to important clinical changes. Although standards exist for assessing these properties, confusion and inconsistency arise because multiple statistics are used for the same property; controversy exists over how to measure responsiveness; many statistics are unavailable on common software programs; strategies for measuring these properties vary; and it is often unclear how to define a clinically important change in patient status. Using data from a clinical trial of therapy for back pain, we demonstrate the calculation of several statistics for measuring reproducibility and responsiveness, and demonstrate relationships among them. Simple computational guides for several statistics are provided. We conclude that reproducibility should generally be quantified with the intraclass correlation coefficient rather than the more common Pearson r. Assessing reproducibility by retest at one-to-two week intervals (rather than a shorter interval) may result in more realistic estimates of the variability to be observed among control subjects in a longitudinal study. Instrument responsiveness should be quantified using indicators of effect size, a modified effect size statistic proposed by Guyatt, or the use of receiver operating characteristic (ROC) curves to describe how well various score changes can distinguish improved from unimproved patients.

Analysis of Variance↗