Higher Intra-individual Variability Research Articles

Clinical Judgment When Using Coagulation Tests during Direct Oral Anticoagulant Treatment: A Concise Review

Because their anticoagulant effect is dose predictable, steady, and little influenced by diet and drugs, laboratory monitoring was deemed unnecessary in trials on venous and arterial thromboprophylaxis with the direct oral anticoagulant drugs (DOACs) rivaroxaban, apixaban, edoxaban, or dabigatran. However, there are special clinical settings in which measurement of their anticoagulant effect may be clinically desired. Because of lack of standardization between reagents employed and their global nature, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) are not generally suitable for accurately assessing the anticoagulant effect of DOACs. The modified (diluted) PT reliably quantifies the anticoagulant effect of rivaroxaban or of apixaban. However, a higher intraindividual variability from one PT reagent to another is found when the data are compared with those obtained with standard PT. The HEMOCLOT (HYPHEN BioMed, France) assay is a modified (diluted) thrombin time (TT) provided with dabigatran calibrators. However, it is performed only in few specialized centers. Anti-factor Xa (anti-FXa) chromogenic assays employ routine automated coagulometers or manual spectrometers, and kits for anti-FIIa assays that measure dabigatran levels and kits for anti-Xa with rivaroxaban calibrators are commercially available. However, no correlation has been identified between any of these tests and clinical outcomes in patients taking any of the DOACs. Thus, currently, there are evidence gaps regarding the role of laboratory testing for surveillance and management of adverse events associated with DOACs. In view of this, in addition to standardization, validation of such assays is mandatory before they can be used to make clinical decisions.

Higher intraindividual variability is associated with more forgetting and dedifferentiated memory functions in old age

Intraindividual trial-to-trial reaction time (RT) variability is commonly found to be higher in clinical populations or life periods that are associated with impaired cognition. In the present study, higher within-person trial-to-trial RT variability in a perceptual speed task is related to more forgetting and dedifferentiation of memory functions in older adults (aged 60–71 years). More specifically, our study showed that individuals in a high-variability group (n=175) forgot more memory scenes over a 1-week retention interval than individuals in the low-variability group (n=174). In contrast, slower RT speed was associated with poorer episodic memory in general, but unrelated to the amount of forgetting. Moreover, results from multiple group latent factor analyses showed that episodic memory and working memory functions were more highly correlated in the high-variability (r=.63) than in the low-variability (r=.25) group. Given that deficits in dopamine (DA) modulation may underlie increases in RT variability, the present findings are in line with (i) recent animal studies implicating DA in long-term episodic memory consolidation and (ii) neurocomputational work linking DA modulation of performance variability to dedifferentiation of cognitive functions in old age.

Impaired performance on the Rapid Visual Information Processing task (RVIP) could be an endophenotype of schizophrenia

The aim of the present study was to investigate whether healthy first-degree relatives of schizophrenia patients show reduced sensitivity performance, higher intra-individual variability (IIV) in reaction time (RT), and a steeper decline in sensitivity over time in a sustained attention task. Healthy first-degree relatives of schizophrenia patients ( n = 23) and healthy control subjects ( n = 46) without a family history of schizophrenia performed a demanding version of the Rapid Visual Information Processing task (RVIP). RTs, hits, false alarms, and the sensitivity index A′ were assessed. The relatives were significantly less sensitive, tended to have higher IIV in RT, but sustained the impaired level of sensitivity over time. Impaired performance on the RVIP is a possible endophenotype for schizophrenia. Higher IIV in RT, apparently caused by impaired context representations, might result in fluctuations in control and lead to more frequent attentional lapses.

Foot Build Registration System (FBRS) to evaluate foot posture: a reliability study with healthy subjects and patients with Charcot-Marie-Tooth disease

To follow the weight bearing foot posture in subjects, a measurement tool using digital photography was developed, Foot Build Registration System (FBRS) (Fig. 1) [M. Van der Cruijsen, Voetvorm registratie systeem, Boxmeer (1999).]. This study's objective was to investigate the reproducibility of FBRS measurements in healthy feet and feet of patients with Charcot-Marie-Tooth disease (CMT). Reproducibility and reliability studies were performed in several foot views in healthy and CMT patients. These studies showed that the variability of the 95% prediction limit depended upon the foot view being studied and whether markers had been drawn. Some individuals had a higher intra-individual variability than others. Limiting data collection to those individuals with a SD<3.5 degrees for a series of five or more photographs per view improved the 95% prediction limits. These varied between 2.8 degrees and 7.7 degrees. If the differences found between registration are greater than the abovementioned, values can be attributed to time or operative management for healthy and CMT patients and not to measurement error.

Heart Fit Brain Fit; A Study Of Intra-individual Variability In Older Subjects

Studies in animals and humans have suggested that exercise training can positively affect cognitive abilities. Lower performance in cognition is associated with higher intra-individual variability on repeated cognitive tests. PURPOSE: To investigate whether a correlation exists between physical fitness and intra-individual variability in cognitive performance in older subjects. METHODS: 8 men and 7 women participated and completed three test sessions, at the same time of the day, following the same protocol, within fourteen days. One session consisted of (i) assessment of the physical fitness (maximal voluntary contraction of the quadriceps muscles, gait velocity, and a cycling test to estimate the maximal oxygen uptake (VO2-max)) and (ii) assessment of the cognitive task performance (Trail Making Test and Stroop colour word Test). RESULTS: Physical fitness was not correlated to intra-individual variability in cognitive performance. Correlations for cognitive tests variability with muscle strength are r=0.28; P=0.33, with gait velocity r=−0.06, P=0.8 and with estimated maximal oxygen uptake r=0.5, P=0.12. Due to a learning effect over the three sessions (ANOVA) it is questionable if the standard deviation and coefficient of variation calculated for cognitive tests represent intra-individual variability. CONCLUSION: This study did not show a correlation between physical fitness and intra-individual variability in cognitive task performance. A larger population and avoidance of a learning effect in testing should be applied to answer the question more properly.

Measurement of striatal D2 dopamine receptor density and affinity with [11C]-raclopride in vivo: a test-retest analysis.

Subacute and long-term stability of measurements of D2 dopamine receptor density (Bmax), affinity (Kd) was studied with positron emission tomography in eight healthy male volunteers. [11C]-Raclopride and the transient equilibrium method were used to measure D2 receptor characteristics. The interval between measurements (scan pairs) was 3 to 7 weeks (subacute) for four subjects and 6 to 11 months (long-term) for four subjects. A test-retest analysis of quantitative measurements of D2 receptor Bmax and Kd was compared with that done on binding potential (BP, Bmax/Kd) measures. In addition, the effect of error in defining the transient equilibrium time (tmax) in the parameter estimation procedure was explored with simulations. The subacute test-retest indicates good reproducibility of D2 receptor density, affinity, and BP ratio measurements with intraclass correlation coefficients of 0.90, 0.96, and 0.86, respectively. The variability of the measurements after 6 to 11 months was slightly higher than that seen in a subacute testing for Kd and more clearly so for binding potential and Bmax. The absolute variability in Bmax (14.5%) measurements was consistently higher than that of Kd (8.4%) or BP (7.9%) both in subacute and long-term measurements. Simulations indicated that the Bmax and Kd estimation procedure is more sensitive to error in the tmax than that for the BP. The results indicate a good overall stability of the equilibrium method with [11C]raclopride for measuring dopamine D2 receptor binding characteristics in the striatum. The BP approach is more stable than Kd and especially Bmax measurements. Error in defining the tmax in particular in the low specific radioactivity scan may be one source of greater variability in Bmax versus BP. However, a higher intraindividual variability in measurements of the D2 receptor Bmax also may include a component of continuous regulation of this parameter over time. These methodologic aspects should be considered in the design and interpretation of longitudinal studies on D2 dopamine receptor characteristics with [11C]-raclopride.