Intra-individual Coefficient Of Variation Research Articles

Association between long-term visit-to-visit blood pressure variability and depression among Chinese middle-aged and older adults

ABSTRACT Background Whether there is a longitudinal association between long-term blood pressure variability (BPV) and subsequent depression among Chinese adults remains inconclusive. Methods This study utilized data from a nationwide cohort of the China Health and Retirement Longitudinal Study, which included participants aged > 45 years without prevalent psychiatric or memory-related diseases. The intra-individual coefficient of variation (CV) and standard deviation (SD) across 3 visits from 2011 to 2015 were used to examine the long-term variability in systolic BP (SBP) and diastolic BP (DBP). The depressive symptoms were examined using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), and moderate-to-severe depression was defined as CES-D-10 ≥ 15. Results A total of 5,249 participants (mean age: 61.4 ± 8.1 years, 46.5% were men) were included in the current analysis. Individuals in the highest quartile of both BP CV and SD were independently correlated with a higher total CES-D-10 score compared to those in the lowest quartile after multivariable adjustment. 1,070 participants (20.4%) had moderate-to-severe depression during the 3-year follow-up period. Participants in the Q4 of SBP and DBP CV had 1.23-fold higher odds (95% CI: 1.01, 1.49) and 1.20-fold higher odds (95% CI: 1.01, 1.41) of moderate-to-severe depression compared to those in Q1. Subgroup analyses revealed that men with higher BP CVs had a greater risk of severe depressive symptoms (p for SBP CV-by-sex interaction = 0.050, p for SBP CV-by-sex interaction = 0.025). Conclusions Depression was common among Chinese middle-aged and older adults and long-term visit-to-visit BPV was positively associated with depressive symptoms, highlighting the importance of implementing intensive prevention strategies for depression and enhancing blood pressure monitors in China.

Investigating the protective effects of mindfulness-based attention training on mind wandering in applied settings.

Mind wandering, a phenomenon in which attention drifts away from the task-at-hand, is associated with deleterious effects on performance and well-being. As such, efforts to curb mind wandering are warranted. Recently, mindfulness training (MT) has been found to protect against mind wandering. Yet, many MT programs are at risk of falling off the implementation cliff due to challenges implementing these programs in applied settings. To mitigate against this, early-stage research in small convenience samples may be necessary to spur stakeholder engagement and collaboration. Herein, the effects of MT on mind wandering were examined via an internal meta-analysis of early-stage studies of a manualized, context-adaptable short-form MT program, referred to as Mindfulness-Based Attention Training (MBAT). Five longitudinal studies (N = 304) were conducted in a variety of organizational cohorts. Self-reported mind wandering and meta-awareness, as well as accuracy (A') and response time variability (intra-individual coefficient of variation, ICV) during performance of the sustained attention to response task (SART) were assessed at baseline (T1) and 4 weeks later (T2) in MBAT and no-training participants. Standardized mean change (SMC) from T1 to T2 significantly differed between MBAT and no-training groups for mind wandering (ΔSMC = -0.387, p < 0.001), meta-awareness (ΔSMC = -0.374, p < 0.001), and ICV (ΔSMC = -0.376, p = 0.043), suggesting potential protective effects in self-reported and performance-based metrics of mind wandering. These results serve as preliminary proof-of-concept support for MBAT's protective effects on mind wandering. Further, they suggest that MBAT is amenable to implementation across a variety of applied and organizational settings and warrants additional research employing larger sample sizes in randomized controlled designs.

Exercise training mitigates the deleterious effects of experimental bed rest on intraindividual variability of executive functioning in older adults: A randomised controlled trial

AbstractBackgroundIn older adults, bed rest can occur because of chronic conditions, injury, surgery, or hospitalization. Extreme levels of physical inactivity due to bed rest initiate a downward spiral in several body systems. Exercise is a countermeasure to many of these changes; nonetheless, little is known about the effect of exercise on older adults’ cognition during bed rest. We thus examined the effects of exercise on the intraindividual variability (IIV) of cognitive performance in older adults exposed to 14 days of experimental 6° head‐down bed rest (HDBR) and whether sex moderates its effects. We chose IIV as our outcome measure because it is more sensitive than traditional summary scores of cognitive performance, albeit no studies have explored exercise effects on older adults’ IIV submitted to bed rest.MethodA non‐blinded, parallel‐group, randomised controlled trial. Twenty‐three healthy older adults aged 55‐65 were randomised to: 1) 14 days of HDBR (CON); or 2) 14 days of HDBR with daily aerobic and strength exercise (EX). Data were collected at baseline, HDBR completion, and end of seven‐day‐recovery. The National Institutes of Health Toolbox Cognitive Battery assessed executive function (Flanker Incongruent and Congruent and Dimensional Change Card Sort) and processing speed (Pattern Comparison). IIV was indexed by intraindividual coefficient of variation (ICV) and residual intraindividual standard deviation (R‐ISD), with R‐ISD as our primary measure of interest. Linear mixed models assessed group differences and the moderator role of sex.ResultAt HDBR completion, EX had significantly lower (better) Flanker incongruent ICV (Estimated mean difference = ‐0.10, 95%CI ‐0.19;‐0.003, p = 0.022) and R‐ISD (Estimated mean difference = ‐3.63, 95%CI ‐6.10;‐1.17, p = 0.005) vs. CON. Sex moderated the effect of exercise; females in EX had significantly lower Flanker incongruent ICV vs. CON (Estimated mean difference = ‐0.23; 95%CI ‐0.34;‐0.12, p&lt;0.001). At the end of the seven‐day recovery, EX had significantly lower Flanker incongruent R‐ISD vs. CON (Estimated mean difference = ‐3.11, 95%CI ‐5.70;‐0.052, p = 0.019). Summary scores and processing speed IIV changes were not statistically significant (ps&gt;0.05).ConclusionExercise during HDBR preserved executive functioning, especially in females. Our findings support the delivery of exercises to older adults during bed rest to preserve their cognitive function.

Cognitive and Exercise Training Improves Intraindividual Variability in Cognitive Performance in Older Adults: Secondary Findings of A Randomized Controlled Trial

AbstractBackgroundIncreased intraindividual variability of cognitive performance is a marker of cognitive decline. Whether computerized cognitive training (CCT) and aerobic exercise counteracts cognitive decline by reducing intraindividual variability is unknown. We investigated the effects of CCT with or without aerobic exercise on reaction time intraindividual variability in older adults.MethodThis was a secondary analysis of an 8‐week randomized controlled trial. Older adults (aged 65‐85 years) were randomized to CCT alone (n = 41), CCT with aerobic exercise (n = 41), or an active control group (n = 42). The CCT group trained using the Fit Brains® platform 3×/week for 1 hour (plus 3×/week of home‐based training). The CCT with aerobic exercise group received 15 min of walking plus 45 min of Fit Brains® 3×/week (plus 3×/week of home‐based training). The control group received sham exercise and cognitive training (3×/week for 1 hour). We extracted reaction times from the Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test (Flanker), and Pattern Comparison Processing Speed Test (PACPS). Intraindividual variability was measured as residual intraindividual standard deviation (residual ISD) of raw reaction time latencies. Residual ISD is an unbiased measure of variability that accounts for within and between participant source of variation that could influence reaction time latencies. We also calculated reaction time intraindividual SD (raw‐score ISD) and intraindividual coefficient of variation (ICV).ResultCompared with the control group, residual ISD improved in a processing speed task (PACPS) following CCT alone (mean difference [95% confidence interval]: ‐0.147 [‐0.230 to ‐0.065], p&lt;0.001) and CCT with aerobic exercise (‐0.111 [‐0.195 to ‐0.027], p&lt;0.01). Also, for processing speed, both CCT (‐0.173 [‐0.261 to ‐0.084], p&lt;0.001) and CCT with aerobic exercise (‐0.122 [‐0.213 to ‐0.032], p&lt;0.01) showed greater reduction in raw‐score ISD compared with controls, while only CCT reduced ICV for this task (‐0.108 [‐0.176 to ‐0.040], p&lt;0.001). Inhibitory attention (Flanker) improved only after CCT with aerobic exercise (congruent = ‐0.128 [‐0.250 to ‐0.006], incongruent = ‐0.121 [‐0.237 to ‐0.005], both p&lt;0.05).ConclusionA CCT program promoted cognitive health via reductions in intraindividual variability of cognitive performance and combining it with aerobic exercise resulted in broader benefits.

Biological variation in thyroid function tests in older adults and clinical implications.

Interpreting thyroid function tests can be challenging due to inherent variation, and the need for tests rises with age. While age-related changes in thyrotropin (TSH) levels are known, the biological variation in older adults remains unclear. We recruited nineteen 65-99-year-old (older adults) without thyroid disease for monthly blood sampling for 1 year. Serum was stored at -20C°, and TSH, total thyroxine (TT4) and total triiodothyronine (TT3) were analysed in random order in a single batch for each participant. Results were compared to test results from 15 euthyroid men aged 24-53 years (younger adults) collected previously using a similar methodology. Interindividual coefficients of variation in older/younger adults were 46.7%/44.0% for TSH, 12.7%/19.5% for TT4 and 14.6%/22.4% for TT3. Intraindividual coefficients of variation (CVI ) were 19.0%/25.4% for TSH, 5.5%/10.8% for TT4 and 6.9%/13.2% for TT3. The index of individuality was below 0.6 for all hormones in all age groups. The number of samples required to determine the homoeostatic set-point at 10% precision in older adults was 14-21 for TSH and 2 for TT4 and TT3. TT4 in older adults was the only parameter in any group with comparable CVI between individuals (p = .22). CVI for TT4 and TT3 was halved in older compared to younger adults with two tests of TT4 needed to describe the individual set-point. Similar CVI between older adults caused TT4 to provide a reliable estimate of thyroid function, and the added value of measuring thyroxine could improve clinical practice.

Masking approaches to analyse plantar pressure data of new and confident walking infants

BackgroundDue to its easy and straightforward use, regional analysis with the “standard” mask is the most common approach for quantifying plantar pressures in infancy. Such a mask, however, identifies foot regions based on typical foot proportions and pressure gradients. Alternatively, the use of a customised mask retaining infants’ feet proportions has not been explored. Research questionDoes a customised mask scaled on infants’ feet improve processing of pressure data collected during walking development compared with a standard mask? MethodsThirteen infants walked across an EMED xl platform. Steps were grouped applying eight foot-regions standard and customised masks. To evaluate masks’ performance, peak pressure (PP) and contact area (CA) were extracted from each region, and mask. Intra-individual coefficients of variation were then calculated for each variable, and compared between masks using a Mann-Whitney U test (p < 0.05). Unsuccessful masks application was reported, expressed as percentage of data loss. ResultsFor CA variation, significant differences were found in all the regions but the lateral toes in new (Z = −0.184, p = 0.8540) and confident walking (Z = −1.562, p = 0.118). For PP variation, a significant difference was found in confident walking within the lateral midfoot (Z = −2.598, p = 0.009). With the standard mask, 22–27 % of data was lost in new and confident walking respectively, compared to 1.6–0 % with the customised. As a result, the customised mask characterised the more variable steps, demonstrating higher variation compared to the standard mask. SignificanceIdentifying foot regions using a mask based on infants’ feet proportions yielded an improved performance compared to the standard mask. With the customised mask, we retained almost all the steps and characterised the variability of the data, thereby providing an appropriate approach for infants’ pressure data processing. Application of the customised mask could therefore be beneficial in future studies analysing highly variable data sets.

Defecatory Function Studies Using the Fecobionics Device Are Repeatable.

Only limited data exist on repeatability of anorectal studies with the established physiological and clinical technologies for assessment of anorectal function. Fecobionics is a new multi-sensor simulated feces that provide data by integrating elements from current tests. To study repeatability of anorectal data obtained with the Fecobionics device. We assessed the database of Fecobionics studies to determine how many repeated studies were done.From a total of 260 Fecobionics studies, 19 subjects with repeated studies using approximately the same protocol and prototype were identified. Key pressure and bending parameters were assessed and the repeatability analyzed using Bland Altman plots. Furthermore, the inter- and intra-individual coefficient of variation (CV) were computed. Fifteen subjects (5F/10M) with repeated studies were normal subjects, three were patients with fecal incontinence and one subject suffered from chronic constipation. The main analysis was conducted on the cohort of normal subjects. The bias for 11 parameters were within the confidence interval, whereas two were slightly outside. The interindividual CV was lowest for the bend angle (10.1-10.7) and between 16.3 and 51.6 for the pressure parameters. The intra-individual CVs were approximately half of the inter-individual CVs, spanning from 9.7 to 27.6. All data from normal subjects were within previously defined normality. The Fecobionics data showed acceptable repeatability with bias within the confidence limits for almost all parameters. The intra-individual CV was much lower than the inter-individual CV. Dedicated large-scale studies are warranted to evaluate the influence of age, sex, and disease on repeatability as well as comparing between technologies.

Plasma endotrophin, reflecting tissue fibrosis, is associated with graft failure and mortality in KTRs: results from two prospective cohort studies.

Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs. In cohort A (57% male, age 53±13years), we measured plasma endotrophin in 690 prevalent KTRs ≥1year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin. In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07-3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73-3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7-7.6)]. Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis. ClinicalTrials.gov NCT02811835.

Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening.

Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

Variability and Seasonal Change of Urinary Selenium, Molybdenum, and Iodine Excretion in Healthy Young Japanese Adults.

Selenium (Se), molybdenum (Mo), and iodine (I) are essential trace elements or nutrients and their adequate intake is essential for human health. These elements in foods are easily absorbed from the digestive tract and excreted predominantly into the urine, and their nutritional status is reflected in urinary excretion; however, information on the variability of urinary excretion is limited. To characterize the urinary Se, Mo, and I concentrations and their intra- and inter-individual coefficients of variation (CV), correlation, and seasonal change, spot urine samples were collected from 24 healthy university students, 10 males and 14 females, with the mean age of 20.6years, for 10 consecutive days in each of the four seasons according to a defined schedule of an interval of 3months throughout 1year. The median Se, Mo, and I concentrations for all urine samples (n = 947) were 52.8, 127.0, and 223μg/L, respectively. The Se and Mo intakes were highest in summer and lowest in spring, while the I intake was highest in autumn and lowest in summer. In all three elements, the intra-individual CVs were smaller than their inter-individual CVs. The log-transformed intra- and inter-individual CVs were 10.5 and 14.7% for Se, 12.3 and 15.1% for Mo, and 15.5 and 18.1% for I. There was no gender difference in Se and I concentrations, while Mo and Mo/Cr values in males were higher than those in females. Our results suggest adequate nutritional status of Se, Mo, and I with a relatively smaller variability of dietary intake except for I in this population.

Glycaemic variability and progression of chronic kidney disease in people with diabetes and comorbid kidney disease: Retrospective cohort study

AimTo investigate the association between glycaemic variability and the development of End-Stage-Kidney-Disease (ESKD) among individuals with diabetes and chronic kidney disease. MethodsA cohort study using UK electronic primary care health records from the Clinical Practice Research Datalink. Glycaemic variability was assessed using a variability score and intra-individual coefficient of variation (CV) of HbA1c. We calculated sub-distribution hazard ratios (sHR) for developing ESKD using competing risk regression analysis. ResultsThere were 37,222 eligible participants (45.5 % male), with a mean age of 76.4 years (SD ± 9.2), and a mean baseline eGFR 40.7 (±10.7) ml/min/1.73 m2. There were 5,086 incidents of ESKD in the follow-up period. The adjusted sHR (95 %CI) for each variability score group, were as follows: 21–40, 1.38 (1.27–1.50); 41–60, 1.54 (1.41–1.68); 61–80, 1.61 (1.45–1.79); and 81–100, 1.42 (1.19–1.68), compared with the group (score 0–20) with least variability. The adjusted sHR for CV were as follows: 6.7–9.9, 1.29 (1.15–1.45); 10.0–13.9, 1.55 (1.39–1.74); 14.0–20.1, 1.79 (1.60–2.01) and ≥20.2, 2.10 (1.88–2.34) compared to reference group 0–6.6. ConclusionsGlycaemic variability was strongly associated with the development of ESKD in people with diabetes and CKD.

Description and validation of a new, simple, easy-to handle, point-of-care technique for measuring erythrocyte aggregation kinetics

Erythrocyte aggregation (EA) is a physiological process by which erythrocytes reversibly stick together within the blood vessels. EA plays a major role in blood viscosity in vivo, thereby impacting blood flow to organs. EA is no doubt greatly important in both physiological and pathophysiological conditions, but the studies its importance calls for are complicated by the lack of a reliable and easy way to measure it. We have developed a new point-of-care technique which can very specifically measure EA initial kinetics (EAK) in 20 s directly on blood samples routinely collected in tubes commonly used in clinical settings. We present the results of the validation studies of this EAK test: A mono-exponential curve explains 99% of EAK variance. EAK is normally distributed in healthy individuals, with an interindividual 15% coefficient of variation and is stable for least one hour after blood collection. Intraindividual coefficient of variation is 2.6%. EA can now be easily measured in any clinical setting.

Evaluation of renal oxygenation by BOLD-MRI in high-risk patients with type 2 diabetes and matched controls.

Diabetic kidney disease (DKD) accounts for ∼50% of end-stage kidney disease. Renal hypoxia is suggested as a main driver in the pathophysiology underlying chronic DKD. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) has made noninvasive investigations of renal oxygenation in humans possible. Whether diabetes per se contributes to measurable changes in renal oxygenation by BOLD-MRI remains to be elucidated. We investigated whether renal oxygenation measured with BOLD-MRI differs between people with type 2 diabetes (T2DM) with normal to moderate chronic kidney disease (CKD) (Stages 1-3A) and matched controls. The repeatability of the BOLD-MRI method was also assessed. In this matched cross-sectional study, 20 people with T2DM (age 69.2 ± 4.7 years, duration of diabetes 10.5 ± 6.7 years, male 55.6%) and 20 matched nondiabetic controls (mean age 68.8 ± 5.4 years, male 55.%) underwent BOLD-MRI analysed with the 12-layer concentric object method (TLCO). To investigate the repeatability, seven in the T2DM group and nine in the control group were scanned twice. A significant reduction in renal oxygenation from the cortex to medulla was found in both groups (P<.01) but no intergroup difference was detected [0.71/s (95% confidence interval -0.28-1.7), P=.16]. The median intraindividual coefficient of variation (CV) varied from 1.2% to 7.0%. T2DM patients with normal to moderate CKD do not seem to have lower renal oxygenation when measured with BOLD-MRI and TLCO. BOLD-MRI has a low intraindividual CV and seems like a reliable method for investigation of renal oxygenation in T2DM.

Fasting pyloric diameter and distensibility by functional endoluminal imaging probe in unsedated healthy volunteers.

Recent studies with functional endoluminal imaging probe (EndoFLIP® ) measure physiologic characteristics of the pylorus. EndoFLIP® has the potential to select optimal candidates for gastric peroral endoscopic myotomy (G-POEM). Normative values of the pylorus using EndoFLIP® have not been established. Twenty-four healthy volunteers (20-56years old; 15 females) underwent unsedated, transoral EndoFLIP® measurements of the pylorus after 8h of fasting. Measurements of diameter (DM), balloon pressure, and distensibility index (DI) of the pylorus were obtained twice over 5min at 40, 50, and 60ml balloon distensions. Pyloric DM at 40, 50, and 60ml balloon distensions were 13.0±2.5, 14.3±1.8, and 17.2±2.0mm, respectively. DM with 60ml distension was notably higher than with 40 and 50ml distensions. Pyloric DI at 40, 50, and 60ml distensions were 10.9±4.8, 11.3±5.8, and 11.1±4.3mm2 /mm Hg, respectively (p=0.86). Linear regression and Bland-Altman plots showed similar distribution of the DM and DI during the second minute compared with the full 5-min measurements at 50ml distension, as well as between two sequential measurements using 50ml distension. With 50ml balloon distension, intraindividual coefficients of variation (COVintra ) for DM and DI were 13.8% and 29.6%, respectively, and interindividual COV (COVinter ) were 12.6% and 51.3%, respectively. Similar reproducibility was obtained with 40ml balloon distension. Unsedated EndoFLIP® can be used to characterize human fasting pyloric diameter and distensibility, with best performance observed with 40ml and 50ml distensions and data collection during the second minute. Normative values reported serve as reference values for future studies.

Repeated Subconcussive Exposure Alters Low-Frequency Neural Oscillation in Memory Retrieval Processing.

Repeated subconcussive head impacts are frequently experienced by athletes involved in competitive sports, such as boxing. The objective of the present study was to investigate the changes in working memory performance and memory retrieval-related neural oscillations in boxing athletes who experienced repeated subconcussive head impacts. Twenty-one boxing athletes (boxing group) and 25 matched controls (control group) completed a modified visual working memory task, and their continuous scalp electroencephalography (EEG) data were collected simultaneously. The behavioral measures and retrieval-related low-frequency neural oscillations were analyzed at each working memory set size in both groups. Subjects in the boxing group showed a reduced mean accuracy, diminished capacity estimates, and slower reaction time at demanding set sizes, and a marginally increased intra-individual coefficient of variation (ICV) for overall set sizes. Additionally, decreased event-related frontal theta synchronization, parieto-occipital alpha desynchronization, and frontal low beta synchronization were observed in the boxing group, suggesting underlying working memory dysfunction for efficient neurocognitive resource employment, inhibition of distracting stimuli, and post-retrieval control in the boxing group. Moreover, a negative correlation was found between frontal beta synchronization and reaction time for most set sizes in both groups. The present study was the first to reveal the underlying working memory deficits caused by the cumulative effects of boxing-related subconcussive head impacts from the perspective of behavior and EEG time-frequency oscillations. Joint analysis of EEG low-frequency oscillations and the innovative task with multiple challenging load conditions may serve as a promising way to detect concealed deficiencies within working memory processing.

Biological Variation of Donor-Derived Cell-Free DNA in Stable Lung Transplant Recipients.

Prior studies demonstrate that donor-derived cell-free DNA (dd-cfDNA) in lung transplant recipients may serve as a marker of allograft injury for detecting allograft rejection and infection. Clinical interpretation of dd-cfDNA requires understanding its biological variation in stable lung transplant patients in order to identify abnormal results suggesting underlying allograft dysfunction. This study establishes the biological variation and reference change values (RCV) of dd-cfDNA in stable lung transplant recipients using an analytically validated assay with an established analytic coefficient of variation (CVA). The AlloSure® assay, a targeted, sequencing-based approach, was used to measure plasma dd-cfDNA in a cohort of lung transplant patients at 4 centers that used dd-cfDNA to monitor for allograft dysfunction in preference to surveillance transbronchial biopsy. Patients with stable allograft function and ≥3 dd-cfDNA samples were included. Intraindividual coefficient of variation (CVI), interindividual CV (CVG), index of individuality (II) and the RCV were calculated. Thirty-five patients with a combined 124 dd-cfDNA samples were included in the final analysis. The median dd-cfDNA was 0.31% (interquartile range 0.18%-0.68%), the 97.5th percentile and 95th percentile were 1.3% and 1.0%, respectively. In 30 stable patients with an average of 3.7 tests, the CVI was 25%, CVG 19%, II 1.33, and RCV 70%. In stable lung transplant patients, fluctuations in dd-cfDNA levels of up to 70% or levels less than 1% are within normal biological variation. With further validation, these thresholds may be incorporated into surveillance monitoring algorithms to identify potentially abnormal results indicating allograft dysfunction.

Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization.

The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies. Sensitized kidney-transplant candidates treated monthly with TCZ (8 mg/kg) for desensitization were retrospectively included. TCZ concentrations were determined by liquid chromatography-tandem mass spectrometry. Seventy-four TCZ concentrations from 10 patients were analyzed. The TCZ trough concentration ranged from <1.0 to 52.5 mg·L−1, with a median of 25.6 mg·L−1 [25th–75th percentiles: 13.2–35.3 mg·L−1). The inter- and intra-individual coefficients of variation were 55.0% and 33.0%, respectively. The TCZ trough concentration was not related to IL-6 (rho = −0.46, p = 0.792), soluble IL-6R (rho = −0.81, p = 0.65) concentrations or reduction of anti-HLA antibodies (mixed-effects model adjusting, effect of TCZ trough concentration: rho = −0.004, p = 0.26). The individual median TCZ concentration tended to be associated with the number of antibodies, with an initial MFI > 3000 that dropped to <3000 after TCZ treatment (rho = 0.397, p = 0.083). TCZ trough concentrations in kidney-transplant candidates treated for desensitization were highly variable. Further studies on larger cohorts are needed to study the possible link between TCZ concentrations and the reduction of anti-HLA antibodies.

Bioequivalence of cefalexin in healthy Chinese subjects.

An earlier three-way crossover study evaluating bioequivalence of 3 cefalexin formulations (capsule for reference, capsule and tablet for test) in healthy subjects in Malaysia showed that the intra-individual coefficients of variation were 9.25% for AUC0-t, 9.54% for AUC0-∞, and 13.90% for Cmax. It is preliminarily stated that cefalexin is not a high-variation product. The here-presented clinical study in China was carried out to analyze the pharmacokinetic properties of two preparations in fasting and postprandial condition to assess the bioequivalence of the test preparation and reference preparation when administered on a fasting and postprandial basis in healthy Chinese subjects and to observe the safety of the test preparation and reference preparation in healthy Chinese subjects. In this trial, a total of 56 eligible subjects were randomly assigned to the fasting group and the postprandial group. The two groups were given 250 mg of the test and reference preparation, respectively. Liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was applied to determine the plasma concentration of cefalexin. PhoenixWinNonlin software (V7.0) was used to calculate the pharmacokinetic parameters of cefalexin using the non-compartmental model (NCA), and the bioequivalence and safety results were calculated by SAS (V9.4) software. The main pharmacokinetic parameters of the test and reference preparations were as follows, the fasting group: Cmax 12.59 ± 2.65 μg/mL, 12.72 ± 2.28 μg/mL; AUC0-8h 20.43 ± 3.47 h×μg/mL, 20.66 ± 3.38 h×μg/mL; AUC0-∞ 20.77 ± 3.53 h×μg/mL, 21.02 ± 3.45 h×μg/mL; the postprandial group: Cmax 5.25 ± 0.94 μg/mL, 5.23 ± 0.80 μg/mL; AUC0-10h 16.92 ± 2.03 h×μg/mL, 17.09 ± 2.31 h×μg/mL; AUC0-∞ 17.33 ± 2.09 h×μg/mL, 17.67 ± 2.45h×μg/mL. The 90% confidence intervals of geometric mean ratios of test preparation and reference preparation were calculated, and the 90% confidence intervals of geometric mean ratios of Cmax, AUC0-10h, and AUC0-∞ were within the 80.00% ~ 125.00% range in both groups. Both Cmax and AUC met the pre-determined criteria for assuming bioequivalence. The test and reference products were bioequivalent after administration under fasting as well as under fed conditions in healthy Chinese subjects. This study may suggest that successful generic versions of cefalexin not only guarantee the market supply of such drugs but can also improve the safety and effectiveness and quality controllability of cefalexin through a new process and a new drug composition ratio.

Validity and reliability of a clinical non-exercise method for assessment of cardiorespiratory fitness using seismocardiography

Abstract Introduction Low cardiorespiratory fitness expressed as a low maximal oxygen consumption (V̇O2max) is associated with cardiovascular disease and all-cause mortality (1). Thus, V̇O2max is recognised as an important clinical tool in the assessment of patients (1,2). However, assessment of V̇O2max by exercise testing is both physically demanding and methodologically challenging and hence the clinical applicability is limited. Purpose Therefore, the aim of this study was to investigate the accuracy and precision of a clinical non-exercise method for assessment of V̇O2max. Methods On three separate days 20 healthy men (n=10) and women (n=10) with varying age (22–72 years) and fitness levels performed two tests for determination of V̇O2max; (a) a non-exercise test using seismocardiography (SCG V̇O2max) and (b) a graded exercise test to voluntary exhaustion on a cycle ergometer based on indirect calorimetry (IC V̇O2max). These tests were performed in order to examine the day-to-day reliability and the validity of SCG V̇O2max, respectively. Furthermore, SCG V̇O2max was assessed twice on each test day to investigate test-retest reliability. The SCG V̇O2max was performed in prone position following a short resting period by placing the SCG recording device on the xiphisternal joint with double adhesive tape. V̇O2max was assessed during a 5-minute recording of the sternal movement using SCG in combination with demographic data of the participants (3). In addition, body composition was measured and a resting blood sample collected each test day. Results On average SCG V̇O2max was 3.3±2.4 ml/min/kg (mean ± 95% CI) lower than IC V̇O2max (p=0.013, SCG V̇O2max: 36.6±3.3 ml/min/kg, IC V̇O2max: 39.9±3.0 ml/min/kg). A significant positive correlation was found between SCG V̇O2max and IC V̇O2max (Pearson, r=0.72, p&amp;lt;0.001). Both SCG V̇O2max and IC V̇O2max was similar between test days (p=0.972) and the intra-individual coefficient of variation was 4.5±2.9% and 4.0±2.5%, respectively. Within each test day SCG V̇O2max was highly correlated (r=0.99, p&amp;lt;0.0001) and no difference was observed between tests (p=0.993). Conclusions The accuracy of the current non-exercise assessment of cardiorespiratory fitness based on seismocardiography is not optimal as SCG V̇O2max was systematically lower than the gold standard assessment applying indirect calorimetry during a graded exercise test. Despite the abovementioned difference, SCG V̇O2max and IC V̇O2max were highly correlated. Furthermore, the precision of SCG V̇O2max is very high as both day-to-day and test-retest reliability were high. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): VentriJect ApS, Copenhagen, Denmark

Does Intensive Mindfulness Training Strengthen Sustained Attention? Examining Individual Differences in Mind Wandering during the Sustained Attention to Response Task

Mindfulness training (MT) has been shown to benefit sustained attention and mind wandering. Yet, few studies have examined whether benefits differ as a function of individual differences in mind wandering. The sustained attention to response task (SART) measured task accuracy (A′), response time variability (response time intraindividual coefficient of variation, ICV), and self-reported mind wandering in participants before (T1) and after (T2) a 1-month MT retreat (n = 56), as well as in a control group (n = 32) who received no MT. Only the retreat group demonstrated increased A′ and reduced mind wandering, but no change in ICV, from T1 to T2. Retreat participants demonstrated reduced ICV compared to the control group only when considering individual differences in mind wandering such that retreat participants with higher levels of mind wandering at T1 demonstrated greater benefits to ICV over time. These findings suggest MT may benefit sustained attention, as seen in changes on both objective and subjective measures, and that considering baseline individual differences may increase our understanding of MT’s benefits to sustained attention.