Influence of Repetitive Contrast Agent Injections on Functional and Molecular Ultrasound Measurements

Quantitative contrast-enhanced ultrasound plays an important role in tumor characterization and treatment assessment. Besides established functional ultrasound techniques, ultrasound molecular imaging using microbubbles targeted to disease-associated markers is increasingly being applied in pre-clinical studies. Often, repeated injections of non-targeted or targeted microbubbles during the same imaging session are administered. However, the influence of repeated injections on the accuracy of the quantitative data is unclear. Therefore, in tumor-bearing mice, we investigated the influence of multiple injections of non-targeted microbubbles (SonoVue) on time to peak and peak enhancement in liver and tumor tissue and of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agents (MicroMarker) on specific tumor accumulation. We found significantly decreasing values for time to peak and a tendency for increased values for peak enhancement after multiple injections. Repeated injections of VEGFR2-targeted microbubbles led to significantly increased tumor accumulation, which may result from the exposure of additional binding sites at endothelial surfaces caused by mechanical forces from destroyed microbubbles.     

Intertester Agreement and Validity of Identifying Lumbar Pain Provocative Movement Patterns Using Active and Passive Accessory Movement Tests

Objective

The purpose of this study was to evaluate the interexaminer agreement and validity of active and passive pain provocation tests in the lumbar spine.

Methods

Two blinded raters examined 36 participants, 18 of whom were asymptomatic and 18 reported subacute nonspecific low back pain (LBP). Two types of pain provocation tests were performed: (1) physiological movements in single (flexion/extension) and, when necessary, combined planes and (2) passive accessory intervertebral movement tests of each lumbar vertebra in prone with the lumbar spine in neutral, flexion, and extension position.

Results

The interobserver agreement in both groups was good to excellent for the identification of flexion (κ = 0.87-1) or extension (κ = 0.65-0.74) as the most painful pattern of spinal movement. In healthy participants, 0% was identified as having a flexion provocative pattern and 8.8% were identified as having an extension provocative pattern. In the LBP group, 20% were identified as having a flexion provocative pattern vs 60% with an extension provocative pattern. The average interexaminer agreement for passive accessory intervertebral movement tests in both groups was moderate to excellent (κ = 0.42-0.83). The examiners showed good sensitivity (0.67-0.87) and specificity (0.82-0.85) to distinguish participants with LBP using this combined examination procedure.

Conclusion

The use of a combination of pain provocative tests was found to have acceptable interexaminer reliability and good validity in identifying the main pain provocative movement pattern and the lumbar segmental level of involvement. These pain provocation tests were able to distinguish participants with LBP from asymptomatic participants and may help clinicians in directing manual therapy treatment.     

Psychometric Properties of Brief-Balance Evaluation Systems Test Among Multiple Populations: A Systematic Review and Meta-analysis

ObjectiveTo synthesize evidence regarding the psychometric properties of the Brief-Balance Evaluation Systems Test (BESTest) in assessing postural controls across various populations.Data SourcesArticles were searched in 9 databases from inception to March 2020.Study SelectionTwo reviewers independently screened titles, abstracts, and full-text articles to include studies that reported at least 1 psychometric property of the Brief-BESTest. There were no language restrictions.Data ExtractionThe 2 independent reviewers extracted data (including psychometric properties of Brief-BESTest) from the included studies. The methodological quality of the included studies was appraised by the Consensus-based Standards for the Selection of Health Status Measurement Instruments checklist, and the quality of statistical outcomes was assessed by the Terwee et al method. A best-evidence synthesis for each measurement property of the Brief-BESTest in each population was conducted.Data SynthesisTwenty-four studies encompassing 13 populations were included. There was moderate to strong positive evidence to support the internal consistency (Cronbach α>0.82), criterion validity (ρ≥0.73, r≥0.71), and construct validity (ρ≥0.66, r≥0.50, area under curve>0.72) of the Brief-BESTest in different populations. Moderate to strong positive evidence supported the responsiveness of the Brief-BESTest in detecting changes in postural controls of patients 4 weeks after total knee arthroplasty or patients with subacute stroke after 4-week rehabilitation. However, there was strong negative evidence for the structural validity of this scale in patients with various neurologic conditions. The evidence for the reliability of individual items and measurement errors remains unknown.ConclusionsThe Brief-BESTest is a valid (criterion- and construct-related) tool to assess postural control in multiple populations. However, further studies on the reliability of individual items and minimal clinically important difference of the Brief-BESTest are warranted before recommending it as an alternative to the BESTest and Mini-BESTest in clinical research/practice.     

Within-Day Test-Retest Reliability of the Timed Up & Go Test in Patients With Advanced Chronic Organ Failure

Objective

To investigate the within-day test-retest reliability of the Timed Up & Go (TUG) test in patients with advanced chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), and chronic renal failure (CRF).

Design

Cross-sectional.

Setting

Patients' home environment.

Participants

Subjects (N=235, 64% men; median age, 70y [interquartile range, 61–77y]; median body mass index, 25.6kg/m² [interquartile range, 22.8–29.4kg/m²]) with advanced COPD (n=95), CHF (n=68), or CRF (n=72).

Interventions

Not applicable.

Main Outcome Measure

Time to complete the TUG test. Three trials were performed on the same day and by the same assessors. The intraclass correlation coefficient (ICC), kappa coefficient, standard error of measurement, and absolute and relative minimal detectable change (MDC) values were calculated.

Results

Good agreement was observed, in general, for both the total sample and subgroups (COPD, CHF, CRF), with ICC values ranging from .85 to .98, and kappa coefficients from .49 to 1.00. However, statistical improvement occurred in the total sample from the first to the second trial with large limits of agreement (mean difference, −.97s; 95% confidence interval, 3.00 to −4.94s; P<.01). The third trial added little or no information to the first 2 trials. For the total sample, a standard error of measurement value of approximately 1.6 seconds, an absolute value of MDC at the 95% confidence level (MDC_95%) of approximately 4.5 seconds, and a relative value of MDC at the 95% confidence level (MDC_95%%) of approximately 35% were found between the first 2 trials, with similar values found for the subgroups.

Conclusions

The TUG test is reliable in patients with advanced COPD, CHF, or CRF after 2 trials. Values of standard error of measurement and MDC may be used in daily clinical practice with these populations to define what is expected and what represents true change in repeated measures.     

Repeatability of Cystometry and Pressure–Flow Parameters in Female Patients

The repeatability of cystometric and pressure–flow data was studied in 31 female patients. The measured parameters had poor correlation coefficients, and logarithmic transforming of the data was generally not warranted. Previous studies and statistical methods of reliability measurement are reviewed. It is suggested as a subject for future studies, that urodynamic measurements are repeated in each patient so that confidence limits can be established within disease entities.     

Estimation of maximum expiratory flow-volume variables in children

Different protocols for pulmonary function testing were evaluated in 611 children, 6-9 years old. Attention was paid to the necessary minimum number of acceptable maneuvers, the necessary maximum number of attempts, and the best of seven different methods for summarizing variables from maximum expiratory flow-volume (MEFV) curves. The results of the study indicate that it is not useful to continue pulmonary function testing after eight attempts. The differences between the results from three or five acceptable maneuvers are not substantial for any method; in children, obtaining three acceptable curves seems sufficient. When flow variables are selected from one acceptable curve, as in the American Thoracic Society (ATS) guidelines, the reproducibility is somewhat less good than in methods in which results of various curves are averaged or selection is made from different curves. The method that has been recommended by the European Community for Coal and Steel for the selection of MEFV variables in teenagers and adults in Europe, was also demonstrated to be suitable for younger children.     

Reproducibility of fetal cardiac flow velocity waveforms at atrioventricular level

Reproducibility of flow velocity waveform recording and analysis was studied at fetal atrioventricular level (mitral and tricuspid valve) in 25 normal pregnancies. The flow velocity parameters studied were peak-E wave velocity, peak-A wave velocity and time-averaged velocity. In each patient, two consecutive measurements were performed (time delay, 15 min) and of each measurement two hardcopies were analyzed. A high reproducibility was achieved for all parameters studied; the coefficients of variation between readings of hardcopies were <2% and the coefficients of variation between tests within patients were -4%.     

Accuracy of the college alumnus physical activity questionnaire

The validity and reproducibility of the Physical Activity Index from the College Alumnus Questionnaire (PAI-CAQ) were determined in 78 men and women (21–59 yr) with a broad range of physical activity habits. The PAI-CAQ was computed as the sum of energy expended in stair climbing, walking, and sports and recreational physical activity recalled from the past week. Data were validated against measures of cardiorespiratory fitness, body fatness, motion detection, and physical activity records. All physical activity was recorded by participants for six 48-hour periods. Each day of the week, including weekends, were represented at least twice in the physical activity records. Age-adjusted correlation coefficients between like activities on the College Alumnus Questionnaire and physical activity records ranged from 0.25 to 0.65 in men and 0.28 to 0.86 in women. Correlations between the PAI-CAQ and validation criteria that reflected total and heavy-intensity physical activities were higher (r = 0.34–0.69, p < 0.05) than for lighter-intensity physical activities and motion detection expressed in MET-min·d⁻¹ and kcal·d⁻¹ (r < 0.35, p > 0.05). Test-retest reproducibility was higher over 1 month (r = 0.72) than over 8 and 9 months (r = 0.34 and 0.43) (p < 0.05). Energy expended in walking and stair climbing was underestimated on the College Alumnus Questionnaire, resulting in lower PAI-CAQ scores, as compared to the physical activity records.     

Reproducibility of M-mode echocardiographic assessment of left ventricular function. Significance of the temporal range of measurements

The aim of this study was to evaluate the reproducibility ofM-mode echocardiography in sequential studies on left ventricular(LV) function. To that end, 3 to 8 serial recordings were performedon 4 groups of healthy subjects (total number, 49) within dissimilartime periods: (1) within 3 h, (2) within 24 h, (3) within 1to 2 weeks and (4) within 14 to 18 months. The examination techniquewas carefully standardized and the recordings were analysedby digitization and computer assistance; the data were averagedfrom 5 beats on each recording. The random variation ofLV transversedimensions and performance was roughly equal in the first 3of these studies; the mean coefficients of variation rangedfrom 1.2 to 1.8% for end-diastolic dimension, from 1.7 to 2.3%for end systolic dimension, and from 2.5 to 3.6% for ejectionfraction. In the long term study the respective mean coefficientswere larger: 3.2%, 3.7% and 5.5%. The coefficients of variationfor estimates of stroke volume, cardiac output, and peripheralvascular resistance ranged from 4.1 to 8.4% in studies completedwithin 1 day or inside Ior2 weeks but increased to 10-15.5%in the long-term study. The beat to beat variability of LV dimensionsand performance, as assessed in a subgroup of 11 subjects, wasroughly equal in quantity to the variability observed in thelong-term study. It is concluded that provided the beat-to-beatvariation is adequately taken into account the reproducibilityof the basic M-mode echocardiographic LV measurements is excellentin short term studies in normal man and is satisfactory in studiesrepeated at intervals of several months or even longer. Theuse of this method to assess changes in cardiac volumes andhaemodynamics should, however, be restricted to short-term studies.