Between-subject Standard Deviation Research Articles

BEAT-TO-BEAT VARIABILITY OF INVASIVE PULSE WAVE VELOCITY: TECHNICAL AND CLINICAL ASPECTS

Objective: Invasive foot-to-foot pulse wave velocity (PWV) is the reference standard for validating new non-invasive PWV-measuring devices. Because of acute haemodynamic variability and data processing issues, PWV shows beat-to-beat variability, which may have important clinical and technical implications. Though current device validation guidelines suggest averaging over at least n = 3 heartbeats to cope with variability, quantitative data on PWV's beat-to-beat variability is lacking. We aimed to quantify this variability and its impact on the confidence of the PWV estimate. Design and method: Pressure waveforms were acquired in n = 82 individuals in the ascending aorta and iliac bifurcation using a dual-tip intra-aortic catheter. For each individual, two datasets were recorded: 1) simultaneous ascending and iliac pressure acquisitions (with ECG), and 2) an additional ascending aorta pressure acquisition (with ECG). Pressure wave foot detection was performed using the intersecting interpolant method. By combining the iliac pressure recording from the first acquisition with the ascending aorta pressure recording from the second acquisition, we evaluated how a sequential acquisition protocol (e.g., catheter pull-back) affects the variability. Furthermore, we estimated how averaging over n consecutive heartbeats affects the standard deviation (SD) of such n-beats-averaged estimate of PWV. Results: PWV was 10.93 ± 4.24 and 11.12 ± 4.42 m/s (mean ± between-subject SD) for simultaneous (PWVsim) and sequential acquisitions (PWVseq; p = 0.002), respectively. The average within-subject SD ( = variability) was 0.48 ± 0.28 m/s for PWVsim and 1.47 ± 1.20 m/s for PWVseq (p < 0.001). This increase in variability was mainly due to the beat-to-beat variability of the ECG R-wave-to-pressure foot time interval, which was ∼2 times higher than that of the simultaneous foot-to-foot transit time (Figure A). Averaging over n = 3 reduced the variability of PWVsim to 0.37 ± 0.25 m/s, while n = 10.24 (median) is required to reach a comparable variability for PWVseq (Figure B). Conclusions: Variability of an invasive foot-to-foot PWV estimate increases considerably when using sequential rather than simultaneous acquisitions. This increase is caused by the high beat-to-beat variability of the duration of the pre-ejection period. To reduce the effective variability of a sequential acquisition to the same level as that of a simultaneous acquisition, averaging over an approximately threefold higher number of heartbeats is required.

Standard Heart Rate Variability Parameters-Their Within-Session Stability, Reliability, and Sample Size Required to Detect the Minimal Clinically Important Effect.

Many intervention studies assume the stability of heart rate variability (HRV) parameters, and their sample sizes are often small, which can significantly affect their conclusions. The aim of this study is to assess the stability and reliability of standard HRV parameters within a single resting session, and to estimate the sample size required to detect the minimal clinically important effect of an intervention. Heart rate was recorded in 50 adult healthy subjects for 50 min in a seated position. Eight standard HRV parameters were calculated from five evenly spaced 5 min intervals. Stability was assessed by comparing the mean values of HRV parameters between the consecutive five test-retest measurements. Absolute reliability was determined by standard error of measurement, and relative reliability by intraclass correlation coefficient. The sample size required to detect a mean difference of ≥30% of between-subject standard deviation was estimated. As expected, almost all HRV parameters had poor absolute reliability but most HRV parameters had substantial to excellent relative reliability. We found statistically significant differences in almost all HRV parameters between the first 20 min and the last 30 min of the session. The estimated sample size ranged from 19 to 300 subjects for the first 20 min and from 36 to 194 subjects for the last 30 min of the session, depending on the selected HRV parameter. We concluded that optimal HRV measurement protocols in a resting seated position should be performed within the first 20 min or between 20 and 50 min after assuming a resting seated position. Future interventional HRV studies should include a sufficient number of subjects and consider the Bonferroni correction according to the number of selected HRV parameters to achieve an appropriate level of study power and precision.

Reliability of kettlebell swing one and five repetition maximum.

Research into the kettlebell swing has increased in the last decade. There has been a paucity of literature assessing an individual's ability to perform the kettlebell swing exercise. The purpose of this study was to determine the test-retest reliability of the one and five repetition maximum (1RM and 5RM) kettlebell swing. Twenty four recreational resistance-trained participants performed an isometric mid-thigh pull (IMTP) and two familiarization sessions followed by three test sessions for each RM load approximately one week apart, using a custom-built plate-loaded kettlebell. On each test occasion, subjects completed a series of warm-up sets followed by 3-4 progressively heavier kettlebell swings to a standardized height until 1RM or 5RM was reached. Test-retest reliability was calculated using the intra-class correlation (ICC) and typical error was represented as the coefficient of variation (CV%) with 90% confidence limits (90% CL). The smallest worthwhile change (SWC%) representing the smallest change of practical importance, was calculated as 0.2 × between-subject standard deviation. The relationship of kettlebell swing performance and maximum strength was determined by Pearson correlation with ±90% CL between the absolute peak force recorded during IMTP and 1RM or 5RM. Results demonstrated a high test-retest reliability for both the 1RM (ICC = 0.97, 90% CL [0.95-0.99]; CV = 2.7%, 90% CL [2.2-3.7%]) and 5RM (ICC = 0.98, 90% CL [0.96-0.99]; CV = 2.4%, 90% CL [1.9-3.3%]), respectively. The CV% was lower than the SWC for both the 1RM (SWC = 2.8%, 90% CL [1.9-3.5]) and 5RM (SWC = 2.9%, 90% CL [1.9-3.6]) kettlebell swing. The correlation between IMTP absolute peak force and the 1RM (r = 0.69, 90% CL 0.43-0.83) was large and very large for the 5RM (r = 0.75, 90% CL [0.55-0.87]). These results demonstrate the stability of 1RM and 5RM kettlebell swing performance after two familiarization sessions. Practitioners can be confident that changes in kettlebell swing 1RM and 5RM performance of >3.6 kg represent a practically important difference, which is the upper limit of the 90% CL.

How much training do English male academy players really do? Load inside and outside of a football academy

To date, no studies have investigated the loads undertaken by elite youth footballers outside of their academy commitments. This study aimed to understand the load of English male academy football players' activity both inside and outside of the academy, as well as, how this load varies between age groups and days. Fifty-two male academy footballers were asked to record the duration, intensity and mode of moderate to vigorous physical activity undertaken outside of their academy training. These data were then combined with session Rating of Perceived Exertion load undertaken inside the academy over the corresponding period. Data were analysed using linear mixed models. The coefficient of variation (CV) was the between-subject standard deviation as a percentage of the mean. The variation of activity types players undertake outside the academy reduced with age. There was no significant difference in the ‘outside of academy’ load between age groups, but there was a significantly greater CV in the Under 15/16 (U15/16) group (CV = 164%) compared to the U12 (CV = 107%) and U13/14 (CV = 119%) age groups ( P = 0.001). For the U12 group, there were no significant between-day differences in load outside of the academy or the combined (inside and outside) load. For the U13/14 and U15/16 groups, there were significant between-day differences in load outside of the academy, as well as, significant between-day differences in the combined load. Practitioners should consider how activities undertaken by players outside of the academy setting contribute to the weekly load periodisation and should modify their training schedules accordingly.

Repeatability of lung clearance index in infants with cystic fibrosis and recurrent wheeze.

To describe the short- and medium-term repeatability of lung clearance index at 2.5%(LCI2.5 ) in infants and calculate the number of patients needed to enroll in a study (N) using LCI2.5 as a primary outcome. An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)]and medium-term repeatability (Bland-Altman method) of LCI2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N2 -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated. Forty infants with CF and 21 with RW were enrolled. Initial N2 -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI2.5 value. In clinically stable patients, LCI2.5 did not significantly change during the 8-month follow-up. Mean LCI2.5 change was -0.08 (1% of baseline) in CF and -0.05 (0.6%) in RW, with 95% limits of agreement being (-1.70; 1.53) in CF and (-1.51; 1.40) in RW patients. N = 23 infants if both intragroup differences of LCI2.5 and minimal difference to be detected would be 2.0. N2 -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies.

Analysis of end-spurt behaviour in elite 800-m and 1500-m freestyle swimming

To analyse the influence of distance, time point of competition, round and finishing position on end-spurt behaviour in swimming. Race results in 800-m and 1500-m freestyle swimming from the last 8 World Championships and 5 Olympic Games (1998–2016) including 1433 races and 528 swimmers were obtained. The end-spurt for each race was determined by means of an End-Spurt Indicator (ESI). The ESI was calculated by dividing the difference between the swim velocity of the last lap (SVLL) and the mean swim velocity of the middle part of the race (SVMP) by the respective individual standard deviation of SVMP. Subsequently, ESI was used as a dependent variable and influences were analysed using a linear mixed model with fixed effects for distance, time point of competition, round and finishing position. An end-spurt was evident in most swims for both race distances. The mean change in swim velocity between the middle part of the race and the last lap was 0.06 ± 0.02 m/s (1.2 ± 0.2 s) in the 800-m and 0.07 ± 0.02 m/s (1.5 ± 0.2 s) in the 1500-m. The finishing position within a race significantly affected the ESI (P < .001, t = 7.28). Specifically, when analysing finals only, ESI was significantly greater in medallists (5.76; quantile: 3.61 and 8.06) compared to non-medallists (4.06; quantile: 1.83 and 6.82; P = .001). The between-subject standard deviation was 1.66 (Cl: 1.42–1.97) with a relative variance component of 23%, while 77% of ESI variance remained unexplained. This is the first study using a newly developed indicator of end-spurt behaviour demonstrating that particularly medallists have a more pronounced end-spurt compared to non-medallists.

Evaluation of airway and circulating inflammatory biomarkers for cystic fibrosis drug development

IntroductionBiomarkers of inflammation in blood and sputum can play a critical role in anti-inflammatory drug development in cystic fibrosis (CF). The objectives of this analysis were to examine relationships between airway and systemic measurements of inflammation, associations between inflammatory biomarkers and FEV1, differences in airway and systemic inflammation by baseline covariates, reproducibility of serum biomarkers, and to assess the effects of freezing and delayed processing on sputum analyte measurements. MethodsWe analyzed baseline and serial concentrations of inflammatory markers in blood and induced sputum collected from individuals with CF ages 10 years and older who participated in a multicenter clinical trial. ResultsAmong circulating biomarkers, serum high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) correlated most strongly with each other (rs = 0.85). Comparing sputum-based inflammation measurements, sputum neutrophil elastase and myeloperoxidase (MPO) were the most highly correlated (rs = 0.88). Markers most strongly correlated with ppFEV1 were serum hsCRP (rs = -0.55), SAA (rs =-0.58), and sputum neutrophil elastase (rs = -0.53). Within-subject standard deviation was consistently lower than between-subject standard deviation for all serum biomarkers. Serum calprotectin and MPO had the highest ratio of between-to-within subject variability. Freezing and delayed sputum processing were not associated with significant differences in measurements of sputum neutrophil elastase, IL-1β, or MPO. ConclusionsAmong the biomarkers analyzed, serum hsCRP and sputum neutrophil elastase are promising candidates to include in CF anti-inflammatory clinical trials to avoid redundancy, minimize variation, and serve as correlates of lung disease severity and change.

Von Willebrand Disease Minimize Menorrhagia (VWDMin) Trial

Von Willebrand Disease Minimize Menorrhagia (VWDMin) Trial

The Effects of Stress Type, Vowel Identity, Baseline f0, and Loudness on the Relative Fundamental Frequency of Individuals With Healthy Voices

Relative fundamental frequency (RFF) has been investigated as a possible acoustic measure to assess laryngeal tension. This study aimed to identify possible factors in RFF stimuli (stress type, vowel identity, baseline f0, and loudness) that might also affect RFF values. Fifteen speakers with healthy voices produced short RFF stimuli (vowel-/f/-vowel; eg, /ɑfɑ/) in different conditions. They produced the stimuli with three different stress types and four different vowels. Participants also produced stimuli in three different baseline f0 conditions and three different loudness conditions. The mean RFF and within- and between-subject standard deviation (SD) of RFF were estimated for each stimuli condition. Stress type had a statistically significant effect on RFF means and within-subject SDs with a large effect size (P < 0.001). A significant but small effect of vowel identity was observed: onset 1 RFF values from /ɑ/ were higher than onset 1 RFF values from /u/ (P < 0.01). Baseline f0 had a significant effect on RFF values with a medium effect size (P < 0.05). Loudness did not have any significant effect on RFF, but onset 1 RFF values produced with soft voice showed an unexpectedly high between-subject SD. This evidence suggests that stress type is the most important factor to consider in RFF measurement. We also conclude that RFF may be somewhat resistant to vowel variation and small differences in baseline f0 and loudness, which may be beneficial in clinical settings.

Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations

IntroductionSweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. MethodsIn subjects with G551D at least 12years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial. ResultsMean overall sweat chloride value (all patients, all tests, n=1062) was 100.8mmol/L (SD 12.7mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9mmol/L (95% CI 7.4–10.6) and within-subject SD was 8.1mmol/L (95% CI 7.5–8.7). Limits of repeatability for repeat measurements were −19.7 to +21.6mmol/L using values from one arm, and −13.3 to 11.8mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. ConclusionAlthough the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.

Feasibility of Using Pseudo-Continuous Arterial Spin Labeling Perfusion in a Geriatric Population at 1.5 Tesla.

ObjectivesTo evaluate the feasibility of using pseudo-continuous arterial spin labeling (pCASL) perfusion in a geriatric population at 1.5-Tesla.Materials and MethodsIn 17 participants (mean age 78.8±1.63 years) we assessed; 1) inter-session repeatability and reliability of resting state perfusion in 27 brain regions; 2) brain activation using finger-tapping as a means to evaluate the ability to detect flow differences; 3) reliability by comparing cerebral blood flow (CBF) with pCASL to CBF with phase contrast (PC-MR).ResultsThe CBF (mean±standard deviation (SD)) for the whole brain grey matter (GM) was 40.6±8.4 and 41.4±8.7 ml/100g/min for the first and second scan respectively. The within-subject standard deviation (SDw), the repeatability index (RI) and intra-class correlation coefficient (ICC) across the 27 regions ranged from 1.1 to 7.9, 2.2 to 15.5 and 0.35 to 0.98 respectively. For whole brain GM the SDw, RI and ICC were 1.6, 3.2 and 0.96 respectively. The between-subject standard deviation (SDB) was larger than the SDw for all regions. Comparison of CBF at rest and activation on a voxel level showed significantly higher perfusion during finger tapping in the motor- and somatosensory regions. The mean CBF for whole brain GM was 40.6±8.4 ml/100g/min at rest and 42.6±8.6 ml/100g/min during activation. Finally the reliability of pCASL against the reference standard of PC-MR was high (ICC = 0.80). The mean CBF for whole brain measured with PC-MRI was 54.3±10.1 ml/100g/min and 38.3±7.8 ml/100g/min with pCASL.ConclusionsThe results demonstrate moderate to high levels of repeatability and reliability for most brain regions, comparable to what has been reported for younger populations. The performance of pCASL at 1.5-Tesla shows that region-specific perfusion measurements with this technique are feasible in studies of a geriatric population.

Effectiveness of High-Intensity Interval Training (HIT) and Continuous Endurance Training for VO2max Improvements: A Systematic Review and Meta-Analysis of Controlled Trials

Enhancing cardiovascular fitness can lead to substantial health benefits. High-intensity interval training (HIT) is an efficient way to develop cardiovascular fitness, yet comparisons between this type of training and traditional endurance training are equivocal. Our objective was to meta-analyse the effects of endurance training and HIT on the maximal oxygen consumption (VO2max) of healthy, young to middle-aged adults. Six electronic databases were searched (MEDLINE, PubMed, SPORTDiscus, Web of Science, CINAHL and Google Scholar) for original research articles. A search was conducted and search terms included 'high intensity', 'HIT', 'sprint interval training', 'endurance training', 'peak oxygen uptake', and 'VO2max'. Inclusion criteria were controlled trials, healthy adults aged 18-45years, training duration ≥2weeks, VO2max assessed pre- and post-training. Twenty-eight studies met the inclusion criteria and were included in the meta-analysis. This resulted in 723 participants with a mean±standard deviation (SD) age and initial fitness of 25.1±5years and 40.8±7.9mL·kg(-1)·min(-1), respectively. We made probabilistic magnitude-based inferences for meta-analysed effects based on standardised thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject SDs for baseline VO2max. The meta-analysed effect of endurance training on VO2max was a possibly large beneficial effect (4.9mL·kg(-1)·min(-1); 95% confidence limits ±1.4mL·kg(-1)·min(-1)), when compared with no-exercise controls. A possibly moderate additional increase was observed for typically younger subjects (2.4mL·kg(-1)·min(-1); ±2.1mL·kg(-1)·min(-1)) and interventions of longer duration (2.2mL·kg(-1)·min(-1); ±3.0mL·kg(-1)·min(-1)), and a small additional improvement for subjects with lower baseline fitness (1.4mL·kg(-1)·min(-1); ±2.0mL·kg(-1)·min(-1)). When compared with no-exercise controls, there was likely a large beneficial effect of HIT (5.5mL·kg(-1)·min(-1); ±1.2mL·kg(-1)·min(-1)), with a likely moderate greater additional increase for subjects with lower baseline fitness (3.2mL·kg(-1)·min(-1); ±1.9mL·kg(-1)·min(-1)) and interventions of longer duration (3.0mL·kg(-1)·min(-1); ±1.9mL·kg(-1)·min(-1)), and a small lesser effect for typically longer HIT repetitions (-1.8mL·kg(-1)·min(-1); ±2.7mL·kg(-1)·min(-1)). The modifying effects of age (0.8mL·kg(-1)·min(-1); ±2.1mL·kg(-1)·min(-1)) and work/rest ratio (0.5mL·kg(-1)·min(-1); ±1.6mL·kg(-1)·min(-1)) were unclear. When compared with endurance training, there was a possibly small beneficial effect for HIT (1.2mL·kg(-1)·min(-1); ±0.9mL·kg(-1)·min(-1)) with small additional improvements for typically longer HIT repetitions (2.2mL·kg(-1)·min(-1); ±2.1mL·kg(-1)·min(-1)), older subjects (1.8mL·kg(-1)·min(-1); ±1.7mL·kg(-1)·min(-1)), interventions of longer duration (1.7mL·kg(-1)·min(-1); ±1.7mL·kg(-1)·min(-1)), greater work/rest ratio (1.6mL·kg(-1)·min(-1); ±1.5mL·kg(-1)·min(-1)) and lower baseline fitness (0.8mL·kg(-1)·min(-1); ±1.3mL·kg(-1)·min(-1)). Endurance training and HIT both elicit large improvements in the VO2max of healthy, young to middle-aged adults, with the gains in VO2max being greater following HIT when compared with endurance training.

WS20.2 Intra-patient variability of sweat chloride concentrations in patients with cystic fibrosis (CF)

Introduction Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although we agree on a cut-of value to diagnose CF, we have only limited information on the natural variability of sweat chloride over time. Still, this information is useful for power calculations in clinical trials. Therefore, we analyzed sweat test results obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. Methods In subjects with G551D at least 12 years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48 weeks. We explored 1062 pilocarpine sweat test values obtained in 78 patients. Results Mean overall sweat chloride value (all patients, all tests) was 100.1 mmol/L (95% CI 96.4–103.7). Using a random coefficient model, the within-subject standard deviation(SD) for sweat chloride was 8.5 mmol/L (95% CI 8.1–8.9) and between-subject SD was 9.8 mmol/L (95% CI 8.1–11.9). Standard deviations were similar with results from the left and from the right arm. Taking the mean measure of both arms rather than the result of one arm decreased within-subject SD by only 0.3 mmol/L. Conclusion Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF had an inherent biological variability that is higher than commonly considered. Further analyses of placebo arm data are crucial to learn more about the natural variability of outcome parameters.

Fructose–Maltodextrin Ratio Governs Exogenous and Other CHO Oxidation and Performance

Fructose coingested with glucose in carbohydrate (CHO) drinks increases exogenous-CHO oxidation, gut comfort, and physical performance. This study aimed to determine the effect of different fructose-maltodextrin-glucose ratios on CHO oxidation and fluid absorption while controlling for osmolality and caloricity. In a crossover design, 12 male cyclists rode 2 h at 57% peak power then performed 10 sprints while ingesting artificially sweetened water or three equiosmotic 11.25% CHO-salt drinks at 200 mL·15 min, comprising weighed fructose and maltodextrin-glucose in ratios of 0.5:1 (0.5 ratio), 0.8:1 (0.8 ratio), and 1.25:1 (1.25 ratio). Fluid absorption was traced with D2O, whereas C-fructose and C-maltodextrin-glucose permitted fructose and glucose oxidation rate evaluation. The mean exogenous-fructose and exogenous-glucose oxidation rates were 0.27, 0.39, and 0.46 g·min and 0.65, 0.71, and 0.58 g·min in 0.5, 0.8, and 1.25 ratio drinks, representing mean oxidation efficiencies of 54%, 59%, and 55% and 65%, 85%, and 86% for fructose and glucose, respectively. With the 0.8 ratio drink, total exogenous-CHO oxidation rate was 18% (90% confidence interval, ±5%) and 5.2% (±4.6%) higher relative to 0.5 and 1.25 ratios, respectively, whereas respective differences in total exogenous-CHO oxidation efficiency were 17% (±5%) and 5.3% (±4.8%), associated with 8.6% and 7.8% (±4.2%) higher fructose oxidation efficiency. The effects of CHO ratio on water absorption were inconclusive. Mean sprint power with the 0.8 ratio drink was moderately higher than that with the 0.5 ratio (2.9%; 99% confidence interval, ±2.8%) and 1.25 ratio (3.1%; ±2.7%) drinks, with total- and endogenous-CHO oxidation rate, abdominal cramps, and drink sweetness qualifying as explanatory mechanisms. Enhanced high-intensity endurance performance with a 0.8 ratio fructose-maltodextrin-glucose drink is characterized by higher exogenous-CHO oxidation efficiency and reduced endogenous-CHO oxidation. The gut-hepatic or other physiological site responsible requires further research.

Discriminant ratio and biometrical equivalence of measured vs. calculated apolipoprotein B100 in patients with T2DM

BackgroundApolipoprotein B100 (ApoB100) determination is superior to low-density lipoprotein cholesterol (LDL-C) to establish cardiovascular (CV) risk, and does not require prior fasting. ApoB100 is rarely measured alongside standard lipids, which precludes comprehensive assessment of dyslipidemia.ObjectivesTo evaluate two simple algorithms for apoB100 as regards their performance, equivalence and discrimination with reference apoB100 laboratory measurement.MethodsTwo apoB100-predicting equations were compared in 87 type 2 diabetes mellitus (T2DM) patients using the Discriminant ratio (DR). Equation 1: apoB100 = 0.65*non-high-density lipoprotein cholesterol + 6.3; and Equation 2: apoB100 = −33.12 + 0.675*LDL-C + 11.95*ln[triglycerides]. The underlying between-subject standard deviation (SDU) was defined as SDU = √ (SD2B - SD2W/2); the within-subject variance (Vw) was calculated for m (2) repeat tests as (Vw) = Σ(xj -xi)2/(m-1)), the within-subject SD (SDw) being its square root; the DR being the ratio SDU/SDW.ResultsAll SDu, SDw and DR’s values were nearly similar, and the observed differences in discriminatory power between all three determinations, i.e. measured and calculated apoB100 levels, did not reach statistical significance. Measured Pearson’s product-moment correlation coefficients between all apoB100 determinations were very high, respectively at 0.94 (measured vs. equation 1); 0.92 (measured vs. equation 2); and 0.97 (equation 1 vs. equation 2), each measurement reaching unity after adjustment for attenuation.ConclusionBoth apoB100 algorithms showed biometrical equivalence, and were as effective in estimating apoB100 from routine lipids. Their use should contribute to better characterize residual cardiometabolic risk linked to the number of atherogenic particles, when direct apoB100 determination is not available.

Intra-day and inter-day reliability of heart rate variability measurement

At present, analysis of heart rate variability (HRV) is becoming widely used as a clinical or research tool. Supported reliability studies for HRV measurement are, however, still limited. The main purpose was to perform an assessment of the absolute and relative reliability of HRV parameters from short-term recordings by means of orthoclinostatic stimulation and to investigate, whether there is a difference in repeating the retest immediately or after several days. The study group consisted of 99 participants (mean age 22 ± 1.24 years). Standard HRV indexes were computed: PT (total spectral power), PHF (high frequency spectral power), PLF (low frequency spectral power) and LF/HF. Absolute reliability was assessed by the standard error of measurement and 95% limits of agreement; relative reliability was assessed by the intraclass correlation coefficient. There was also an estimate of the sample size needed to detect the mean difference ≥ 30% of the between-subject standard deviation. In conclusion, a large random variation (within individuals) of HRV parameters was revealed, regardless of whether the retest was repeated immediately or with an interruption. For most HRV parameters (particularly in the immediately repeated test-retest), however, random variation represents a limited portion of the between-subject variability.

Heart rate variability reproducibility during exercise

The use of heart rate variability (HRV) parameters during exercise is not supported by appropriate reliability studies. In 80 healthy adults, ECG was recorded during three 6 min bouts of exercise, separated by 6 min of unloaded cycling. Two bouts were at a moderate intensity while the final bout was at a heavy exercise intensity. This protocol was repeated under the same conditions on three occasions, with a controlled start time (pre-determined at the first visit). Standard time and frequency domain indices of HRV were derived. Reliability was assessed by Bland–Altman plots, 95% limits of agreement and intraclass correlation coefficients (ICC). The sample size required to detect a mean difference ≥30% of the between-subject standard deviation was also estimated. There was no systematic change between days. All HRV parameters demonstrated a high degree of reproducibility during baseline (ICC range: 0.58–0.75), moderate (ICC: 0.58–0.85) and heavy intensity exercise (ICC range: 0.40–0.76). The reproducibility was slightly diminished during heavy intensity exercise relative to both unloaded baseline cycling and moderate exercise. This study indicates that HRV parameters can be reliably determined during exercise, and it underlines the importance of standardizing exercise intensity with regard to fitness levels if HRV is to be reliably determined.

Reproducibility of 3D 1H MR spectroscopic imaging of the prostate at 1.5T

To determine the reproducibility of 3D proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of the human prostate in a multicenter setting at 1.5T. Fourteen subjects were measured twice with 3D point-resolved spectroscopy (PRESS) (1)H-MRSI using an endorectal coil. MRSI voxels were selected in the peripheral zone and combined central gland at the same location in the prostate in both measurements. Voxels with approved spectral quality were included to calculate Bland-Altman parameters for reproducibility from the choline plus creatine to citrate ratio (CC/C). The repeated spectroscopic data were also evaluated with a standardized clinical scoring system. A total of 74 voxels were included for reproducibility analysis. The complete range of biologically interesting CC/C ratios was covered. The overall within-voxel standard deviation (SD) of the CC/C ratio of the repeated measurements was 0.13. This value is equal to the between-subject SD of noncancer prostate tissue. In >90% of the voxels the standardized clinical score did not differ relevantly between the measurements. Repeated measurements of in vivo 3D (1)H-MRSI of the complete prostate at 1.5T produce equal and quantitative results. The reproducibility of the technique is high enough to provide it as a reliable tool in assessing tumor presence in the prostate.

Non-HDL-cholesterol as valid surrogate to apolipoprotein B100 measurement in diabetes: Discriminant Ratio and unbiased equivalence

BackgroundApolipoprotein B100 (apoB) is a superior indicator of CV risk than total or LDL-C. Non-HDL-C represents a simple surrogate for apoB in hypertriglyceridemic and/or T2DM patients. ApoB and non-HDL-C show high correlation, although the degree of mutual concordance remains debated in CV risk evaluation.ObjectivesWe used the Discriminant Ratio (DR) methodology to compare the performance of non-HDL-C with that of apoB to rank diabetic patients according to dyslipidemia and to establish the underlying relationship between these variables taking measurement noise and intra-/intersubject variation into account, and to derive an unbiased equivalence equation.MethodsFasting total C, HDL-C, apoB and triglycerides were measured in 45 diabetic patients. The DR of the underlying between-subject standard deviation (SD) to the within-subject SD was calculated from duplicates. Correlation coefficients between pairs were adjusted to include an estimate of the underlying correlation.ResultsMean values [day 1 (1SD)] were 143 (36) mg/dl (non-HDL-C) and 98 (24) mg/dl (apoB). The DR's of both parameters were similar (1.76 and 1.83) (p = 0.83). Pearson's product-moment correlation coefficient between tests was very high (0.94), reaching unity (1.00) after attenuation adjustment. The unbiased equation of equivalence relating apoB to non-HDL-C had a slope of 0.65 and an intercept of 6.3 mg/dl.ConclusionsThe discrimination power of non-HDL-C is similar to that of apoB to rank diabetic patients according to atherogenic cholesterol and lipoprotein burden. Since true correlation between variables reached unity, non-HDL-C may provide not only a metabolic surrogate but also a candidate biometrical equivalent to apoB, as non-HDL-C calculation is readily available.

The Minimum Frequency of Glucose Measurements from Which Glycemic Variation Can Be Consistently Assessed

While there has been much debate about the clinical importance of glycemic variation (GV), little attention has been directed to the properties of data sets from which it is measured. The purpose of this study is to assess the minimum frequency of glucose measurements from which GV can be consistently and meaningfully measured. Forty-eight 72 h continuous glucose monitoring traces from children with type 1 diabetes were assessed. Measures of GV included standard deviation (SD), mean amplitude of glycemic excursion (MAGE), and continuous overlapping net glycemic action (CONGA1-4). Measures of GV calculated using 5 min sampling were designated as the 100% or "best estimate" value. Calculations were then repeated for each patient using glucose values spaced at increasing intervals. For each of the specified sampling frequencies, the ratio (%) of the between-subject SD based on the reduced subset of data to the estimate of the SD based on the full 5 min sampling data set was calculated. As the interval between observations increased, so did the variability of the estimators of GV. Standard deviation exhibited the least systematic change at all measurement intervals, and MAGE exhibited the greatest systematic change. In patients with type 1 diabetes, GV as measured by SD or CONGA4, becomes unreliable if observations are more than 2-4 h apart, and estimates of MAGE become unreliable if glucose measurements are more than 1 h apart. MAGE is more unstable and prone to random measurement error than either SD or CONGA. The frequency of glycemic measurements is thus pivotal when selecting a parameter for measurement of GV.