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PubMed2003

Individual difference variables, affective differentiation, and the structures of affect.

Methodological arguments are usually invoked to explain variations in the structure of affect. Using self-rated affect from Italian samples (N=600), we show that individual difference variables related to affective differentiation can moderate the observed structure. Indices of circumplexity and congruence coefficients to the hypothesized target were used to quantify the observed structures. Results did not support the circumplex model as a universal structure. A circular structure with axes of activation and valence was approximated only among more affectively differentiated groups: students and respondents with high scores on Openness to Feelings and measures of negative emotionality. A different structure, with unipolar Positive Affect and Negative Affect factors, was observed among adults and respondents with low Openness to Feelings and negative emotionality. The observed structure of affect will depend in part on the nature of the sample studied.

Adolescent↗
PubMed1990

[Serum levels of various free amino acids in patients with collagen pneumoconiosis].

The purpose of the study was the evaluation of blood serum concentration of selected free amino acids of collagen (arginine, glycine, glutamic acid with threonine, leucine with isoleucine and alanine) in patients with diagnosed collagen pneumoconiosis caused by industrial dust containing free silica. The group studied consisted of 17 men aged 41 to 60 years with radiologically diagnosed pneumoconiosis as p, q, or r type. The exposure time to silica dust was equal to 17 years on average. The control group consisted of 21 healthy subject, men aged 16 to 59 years. The serum amino acids were isolated using paper chromatography (the cylindrical technique) and quantitative measurements were performed by means of evaluation of absorption of colorful eluates of DYDA complex with cadmium ions. The results obtained were statistically evaluated using the Student t test at 95% probability level. The statistical analysis of results showed important individual variability of amino acid determined and individual variability coefficients were in range 28.7-39.8%. The significant increase of the glycine and of glutaminic acid with threonine levels (36.4% and 62.2%, respectively) and significant decrease in the level of leucine with isoleucine (16.5%) has been stated in patients if compare with the control group. In patients with collagen pneumoconiosis the levels of arginine or alanine remained within the normal range.

Adult↗
PubMed2005

Effects of estradiol and progesterone on the variability of the micronucleus assay.

To investigate chromosomal radiosensitivity of lymphocytes the micronucleus (MN) assay has been used for many years. The results of these studies suggest the use of the MN assay as a biomarker for cancer predisposition. However, the MN assay has still some limitations associated with the reproducibility and sensitivity. Especially a high intra-individual variability has been observed. An explanation for this high intra-individual variability is not yet available. In literature it is suggested that the high variability among females is attributable to hormonal status. In this study we investigated if the high intra-individual variability in micronucleus formation in lymphocytes of females after in vitro exposure to ionising radiation is caused by variations in hormone levels of estradiol (E2) and progesterone (PROG). For this, the MN assay was performed on blood samples of 18 healthy women during 7 consecutive weeks while the estradiol and progesterone levels were determined at the same time. The MN assay was also examined in cultures of isolated blood lymphocytes with estradiol or progesterone levels added in vitro. The results demonstrated that estradiol and progesterone levels have no influence on the variations in radiation-induced MN yields observed in blood samples of healthy women. These conclusions were confirmed by the "in vitro" experiments as no correlation between the MN yields and the concentrations of hormones (estradiol or progesterone) added in vitro to isolated lymphocytes cultures was observed.

Adult↗
PubMed2002

Variability within individuals of plasma ionic magnesium concentrations.

BACKGROUND: With the invention of the ion-selective electrode (ISE), ionic magnesium (iMg) is a common blood assay. This could be advantageous, as iMg is the biologically active form of Mg. There is some evidence that iMg has considerable within subject variability. RESULTS: Individual ranges averaged.08 mmol/L (range.05 to.14). Coefficients of variation (CV) ranged from 3% to 7% (mean 4%) while analytical variation was determined to be 2.3%. Biological variability thus accounts for almost half of the variability, which is clinically significant, as 9 of the 13 subjects recorded at least one value below a reference range of.46 -.60 mmol/L. A significant within-day variation (p <.001) was noted, with differences between 7:00 and 10:00 as well as 10:00 and 22:00. Between day variations were not significant (p =.56). CONCLUSIONS: A plausible explanation of this data is that iMg has a circadian rhythm. Thus, cautious interpretation of single iMg values is warranted until future research determines the nature of iMg variability.

Adult↗
PubMed2002

Modeling treatment effects on binary outcomes with grouped-treatment variables and individual covariates.

During evaluation of treatment effects in observational studies, confounding is a constant threat because it is always possible that patients with a better prognosis, not adequately characterized by measured covariates, are chosen for a specific therapy. Ecologic analyses may avoid confounding that would be present in analysis at the individual level because variations in regional or hospital practice may be unrelated to prognosis. The authors used simulated data with an excluded confounder to evaluate the reliability and limitations of the grouped-treatment approach, a method of incorporating an ecologic measure of treatment assignment into an individual-level multivariable model, similar to the instrumental variable approach. Estimates based on the grouped-treatment approach were closer to the true value than those of standard individual-level multivariable analysis in every simulation. Furthermore, confidence intervals based on the grouped-treatment approach achieved approximately their nominal coverage, whereas those based on individual-level analyses did not. The grouped-treatment approach appears to be more reliable than standard individual-level analysis in situations where the grouped-treatment variable is unassociated with the outcome except via the actual treatment assignment and measured covariates.

Confounding Factors, Epidemiologic↗
PubMed2006

Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients.

OBJECTIVE: The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. METHODS: The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. RESULTS: The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid E(max) model. The EC(50) values of lorazepam for the sedation scores equal or larger than 2-5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1,100 and 2,200 ng/ml. Inter-individual variability in the EC(50) values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. CONCLUSION: The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in "ease of titration" between lorazepam and midazolam are unrelated to pharmacodynamic factors.

Adult↗
PubMed2004

Longitudinal changes in the well-being of Japanese caregivers: variations across kin relationships.

This study examined how the psychological well-being of Japanese caregivers changed over time; it also examined the variation across kin relationships with care recipients. Three interviews over the course of 30 months were conducted with a representative sample of community-dwelling caregivers of frail elderly persons living in a Tokyo suburb. Latent growth modeling demonstrated that mean levels of both depression and emotional exhaustion worsened over time. Change in emotional exhaustion over time showed significant individual variability, whereas change in depression showed little individual variability. Although wife caregivers tended to experience the worst trajectory of emotional exhaustion, daughters-in-law also showed a similar negative trend. The difference in individuals' well-being trajectories by kinship may be explained partly by differences in care recipients' disabilities.

Affect↗
PubMed1994

Auditory brainstem response (ABR) peak amplitude variability reflects individual differences in cochlear response times.

Previously, it was shown [Don et al., J. Acoust. Soc. Am. 94, 2135-2148 (1993)] that cochlear response times are gender specific and about 13% shorter in females than in males. It is also suggested that one of the possible reasons click-evoked auditory brainstem response (ABR) waveforms recorded from females are better defined and have larger amplitudes than those of males is due to a sex difference in cochlear response times leading to better synchronization of the cochlear output across the frequency regions. Variability in cochlear response times would also lead to variability in click evoked ABR amplitudes. The high-pass noise masking derived ABR technique was used to investigate the effect of normalizing the individual temporal variability at the neural and cochlear levels. This involved adjusting for differences in neural conduction time (I-V delay) by a compression or expansion of the derived ABR waveforms and by adjusting for differences in cochlear response times by a shift of the derived ABR waveforms. A summation of the compressed and shifted ABRs results in a normalized unmasked ABR waveform that can then be compared for amplitude variability with the unprocessed unmasked ABRs. Compensation for the neutral I-V variability had little effect while compensation for cochlear response times, particularly the delay between the 5.7- and 2.8-kHz regions, greatly affected the amplitude of wave V of the compounded ABR. This work provides a better understanding of the significant relationship between cochlear response times and variability of the ABR peak amplitudes.

Adolescent↗
PubMed1995

Variability in airway conductance and lung volume in subjects with asthma.

Variability in airway conductance (Gaw) and lung volume (TGV) was studied in 26 subjects with moderately severe asthma during a 9-week period. Specific airway conductance (SGaw) was calculated as Gaw:TGV. There was considerable inter-individual variability in airway conductance, and a smaller variability in TGV. Airway conductance (SGaw) showed an eight-fold difference and TGV a three-fold difference between smallest and largest values. The intra-individual variability was less, with a range of +/- 55% (SGaw) and +/- 12% (TGV) of the grand mean, respectively. The error of the method contributed only marginally to the variations in airway conductance. These data for spontaneous variability of conductance facilitate, for example, the assessment of the clinical importance of changes in lung function seen after exposure to air pollutants in chamber studies. Furthermore, the substantial inter-individual variability in conductance argues against comparing samples of asthmatic subjects in polluted and non-polluted areas, and in favour of prospective studies of cohorts of subjects with asthma.

Airway Resistance↗
PubMed2005

Characterization and consequences of pain variability in individuals with fibromyalgia.

OBJECTIVE: A growing body of evidence suggests that real-time electronic assessments of pain are preferable to traditional paper-and-pencil measures. We used electronic assessment data derived from a study of patients with fibromyalgia (FM) to examine variability of pain over time and to investigate the implications of pain fluctuation in the context of a clinical trial. METHODS: The study group comprised 125 patients with FM who were enrolled in a randomized, placebo-controlled trial of milnacipran. Pain intensity levels were captured in real time by participants using electronic diaries. Variability in pain was assessed as the standard deviation of pain entries over time (pain variability index [PVI]). RESULTS: Substantial between-subject differences in pain variability were observed (mean +/- SD PVI 1.61 +/- 0.656 [range 0.27-4.05]). The fluctuation in pain report was constant over time within individuals (r = 0.664, P < 0.001). Individuals with greater variability were more likely to be classified as responders in a drug trial (odds ratio 6.14, P = 0.006); however, this association was primarily attributable to a greater change in pain scores in individuals receiving placebo (r = 0.460, P = 0.02) rather than active drug (r = 0.09, P > 0.10). CONCLUSION: Among individuals with FM, there were large between-subject differences in real-time pain reports. Pain variability was relatively constant over time within individuals. Perhaps the most important finding is that individuals with larger pain fluctuations were more likely to respond to placebo. It is not clear whether these findings are applicable only to patients with FM or whether they may also be seen in patients with other chronic pain conditions.

Cyclopropanes↗
PubMed1997

Variability of the limb joint patterns of sound horses at trot.

The reproducibility of gait variables for sound horses is essential for the interpretation of their modifications by locomotor disorders. Therefore, the purpose of this study was to evaluate the variability of the limb joint angle patterns in a population of sound horses while they trotted in the conditions of the routine lameness examination (slow trot, just held by hand, on a track, outdoors). The kinematics of 14 French Saddle horses was recorded using a 3-dimensional (3D) kinematic analysis system. Angle-time diagrams were established in the sagittal plane and their intra- and inter-individual variabilities were evaluated for the whole stride. Horses spontaneously repeated tests at constant speed. The intra- and inter-individual variabilities were low. These values were different from one joint to another and they increased distally. The maximum values were reached by the fetlock and coffin joints. Inter-individual compared to intra-individual variability was 0.9 to 1.9 times greater. There was a high correlation between mean angle-time and mean individual diagrams established for the whole population. It was concluded that it is possible to repeat similar tests with horses trotting in the conditions of the lameness examination. In an homogeneous population, each horse adopts a constant angular pattern that is very close to that of other horses. Since mean angle-time diagrams established on a sound population are highly representative of each mean individual angle pattern, they can be considered as reference data for the further analysis of the pathological gait.

Animals↗
PubMed1993

Infertility: a non-event transition.

OBJECTIVE: To determine the predictive validity of four transition variables and seven individual variables in differentiating between individual responses to infertility. DESIGN: Forty-three primary infertile women and 28 men attending a general infertility treatment clinic voluntarily agreed to participate in this cross-sectional study and completed five standardized instruments on a one-time-only basis. RESULTS: Adjustment to infertility was related to positive self-esteem, internal locus of control, higher socioeconomic status, and moderate age. High levels of anxiety and distress were related to low self-esteem, undifferentiated sex role identity, and advanced age. Actual and perceived duration of infertility were factors also related to participants' responses to infertility. CONCLUSION: Results highlight the importance of psychological assessment and continuing support in the management and treatment of infertility, with concerns being raised regarding the advisability of protracted medical intervention.

Adaptation, Psychological↗
PubMedDate not supplied

[Pulmonary function indices: variability, predicted values and discriminating power (author's transl)].

Flow/volume curves, single-breath N2 washout curves, single-breath and steady-state carbon monoxide diffusion tests were performed on 229 firemen (aged 20 to 55 years) and repeated one week later on 183 of them. According to a questionnaire, 58 were asymptomatic non-smokers, 130 were asymptomatic smokers and 34 were smokers with symptoms of cough with or without sputum. Intra-individual variability of indices determined from tests performed at a week interval is not always aleatory and it is different in the three groups. It is the same for inter-individual variability which is lowest in asymptomatic smokers and highest in symptomatic smokers. Age and height were the most important factors in inter-individual variability for spirometric indices but do not affect the variability of the slope of N2 curve (delta N2) or fractional uptakes of CO. The ratio of residual variance (adjusted for age and morphometric parameters) on intra-individual variance indicated the choice of "sensitive" functional indices. This choice may be reached in a different way by comparison of means of groups distinguished according to symptoms or smoking habits. Reference equations for indices derived from each test are proposed. The problem of the choice of "sensitive" indices and the problem of reference groups and reference values are discussed.

Adult↗
PubMed1990

Variability in man of the levels of some indices of nutritional status over a 60-d period on a constant diet.

The biological variability of the values of various biochemical indices used for the assessment of the nutritional status of man was investigated in 4 healthy male volunteers (mean age 23 years). They were given a constant diet for 60 d, with the nutrient intake at the level of the Dutch recommendations. Blood was collected twice a week and 24-h urine samples on all 60 d; furthermore, on one day blood was collected every 2 h. Two months after the 60-d constant diet period the intra-individual variability of the various indices was studied once more, this time under habitual dietary practices. The intra-individual variability of urinary excretion of the vitamins B1 and B2 turned out to be rather high (coefficient of variation (CV) ranging from 11 to 25 per cent). Despite a constant sodium intake throughout the study, the variability of urinary Na excretion was also high (mean CV 16 per cent); the level of CV did not improve when the excretion was expressed on the basis of creatinine. Levels of serum HDL- and total cholesterol were fairly constant, both over the 60-d period and during the day (CV 2.5-7 per cent). The CV within subjects for vitamin B1, B2 and B6 concentrations in blood ranged from 6 to 12 per cent, the variations of the corresponding erythrocyte enzyme activities were smaller. It is remarkable that the CV within subjects of most variables studied was not higher during the period on the habitual diet. We conclude that casual blood sampling is insufficient for an evaluation of the vitamin B status of an individual. The high intra-individual variability of 24-h vitamin B1 and B2 urinary excretions indicates that in the assessment of the vitamin status or intake of an individual the importance of these excretion figures is limited. The 'a-values' of the B vitamins may predict vitamin status better than the concentrations of the vitamins in blood or the activities of the corresponding enzymes. The variability of the parameters of vitamin B status over the day (CV 3-11 per cent) suggests that the values of these parameters depend on the time of the day at which samples are taken.

Adult↗
PubMed2006

Population analysis of the pharmacokinetics and the haematological toxicity of the fluorouracil-epirubicin-cyclophosphamide regimen in breast cancer patients.

PURPOSE: The aims of the study were (a) to characterise the pharmacokinetics (PK), including inter-individual variability (IIV) and inter-occasion variability (IOV) as well as covariate relationships and (b) to characterise the relationship between the PK and the haematological toxicity of the component drugs of the fluorouracil (5-FU)-epirubicin (EPI)-cyclophosphamide (CP) regimen in breast cancer patients. PATIENTS AND METHODS: Data from 140 breast cancer patients, either within one of different studies or in routine clinical management, were included in the analyses. The patients were all treated with the fluorouracil-epirubicin-cyclophosphamide (FEC) regimen every third week for 3-12 courses, either in standard doses, i.e. 600/60/600 mg/m(2) of 5-FU, EPI and CP, respectively, or according to a dose escalation/reduction protocol (tailored dosing). PK data were available from 84 of the patients, whereas time-courses of haematological toxicity were available from 87 patients. The data analysis was carried out using mixed effects models within the NONMEM program. RESULTS: The PK of 5-FU, EPI and 4-hydroxy-cyclophosphamide (4-OHCP), the active metabolite of CP, were described with a one-compartment model with saturable elimination, a three-compartment linear model and a two-compartment linear model, respectively. No clinical significant correlation was found between PK across drugs. The unexplained variability in clearance was found to be less within patients, between courses (inter-occasion variability, IOV) than between patients (inter-individual variability, IIV) for EPI and 5-FU. For 4-OHCP, however, the IIV diminished by approximately 45% when significant covariates were included and the final population model predicts an IIV that is equal to IOV. Significant covariates for elimination capacity parameters were serum albumin (5-FU, EPI and 4-OHCP), creatinine clearance (5-FU), bilirubin (EPI) and body surface area (BSA) (4-OHCP). Elimination capacity of 5-FU and EPI was not related to BSA and for none of the studied drugs did body weight explain the PK variability. The time-course of haematological toxicity after treatment was well described by a semi-physiological model that assumes additive haematological toxicity between CP and EPI with negligible contribution from 5-FU. The influence of G-CSF could be incorporated into the model in a mechanistic manner as shortening the maturation time to 43% of the normal duration and increasing the mitotic activity to 269% of normal activity. CONCLUSIONS: The models presented describe the dose-concentration-toxicity relationships for the FEC therapy and may provide a basis for implementation and comparison of different individualisation strategies based on covariates, therapeutic drug monitoring and/or pharmacodynamic (PD) feedback. The PD model extends on previous semi-mechanistic models in that it also takes G-CSF administration into account.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The development and validation of a digital peak respiratory pressure monitor and its characteristics in healthy human subjects.

A digital peak respiratory pressure (DPRP) monitor for determining maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was developed using a pressure transducer and an analog to digital converter. It was calibrated using a mercury manometer. Human studies were conducted in healthy young adults in order to determine within-subject and inter-individual variability, as well as diurnal variations and gender differences in maximal respiratory pressures. The calibration studies for the instrument indicated that the instrument recorded accurate pressures, with little temporal drift. Within-subject variability was generally low while inter-individual variability was higher and significant. Gender differences were similar to those recorded in literature for other racial groups. The DPRP monitor described is inexpensive, accurate and portable, making it ideal for use at the patient's bedside.

Adult↗
PubMed2001

[Influence of experience on intra- and interindividual variability in assessing peripheral endothelial dysfunction with high resolution ultrasound].

UNLABELLED: The non-invasive evaluation of endothelial dysfunction with high-resolution ultrasound has become a widely accepted tool in determination of high-risk subjects for early atherosclerosis. Furthermore it is often used as intermediate outcome in intervention studies. AIM: We examined the influence of examiner experience on intra- and inter-individual variability in the measurement of flow-associated vasodilation (FAD) independent of automated analysis systems. METHOD: FAD was measured on two occasions in 7 and 8 subjects respectively (mean age 32 +/- 3 years) by two investigators after different prior training procedures with a 13 MHz linear transducer (LA14A, ESAOTE Biomedica). RESULTS: The intra-individual variability expressed as median absolute difference in the measurements of FAD was 1.1 % (range from 0.03 % to 3.2 %) for examiner one with an experience of more than 50 FAD measurements through former studies and 2.9 % (range from 1.6 % to 9.2 %) for examiner two with only 10 training examinations under supervision. By a further training period of two months, with an increase of examinations of additional 20 measurements by both examiners, the intra-observer variability could be dropped to 0.9 % (range from 0.03 % to 1.3 %) for examiner two (p = 0.0025) with no significant change for examiner one (median 0.6 % with a range from 0.14 % to 3.7 %). As expected, the inter-individual variability was not influenced by this further training (median 1.0 % with a range of 0.5 % to 3.6 % versus a median of 1.6 % with a range from 0.15 % to 7.5 %). CONCLUSION: 30 training measurements of FAD under supervision should be regarded as minimum requirement for valid determination of endothelial function. The reachable result for the intra-observer variability is thereby within the range of computed analysis systems.

Adult↗
PubMed1989

Variability of three standard neurophysiological techniques in established symptomatic diabetic polyneuropathy.

The reproducibility of three standard neurophysiological techniques (motor and sensory nerve conduction velocities, vibration perception threshold and mean expiratory: inspiratory electrocardiographic R-R ratio) was determined from duplicate measurements approximately four weeks apart in 50 patients with chronic symptomatic diabetic polyneuropathy. There was no change in average glycaemic control (mean +/- SD) between the measurements (HbA1 10.7 +/- 2.0 vs. 10.4 +/- 2.1% at zero and four weeks respectively). While there were no significant differences in the mean values at zero and four weeks for any technique considerable intra-individual variability was observed in several measurements. Mean coefficients of variation (CV) for motor nerve conduction velocity ranged from 9.8% (ulnar nerve) to 10.7% (median) to 12.2% (peroneal nerve). Variability in sensory nerve conduction velocities (CVs 8.6, 8.7 and 14.7% for radial, ulnar and sural nerves respectively) was complicated by a high proportion of unrecordable action potentials. Duplicate action potentials were recordable from the sural nerve in only 15 (30%) patients. The highest intra-individual variability was observed in measurements of vibration perception threshold with CVs of 21.0% (thumb) and 18.0% (hallux). The apparently satisfactory CV of 3.6% for the cardiac E:I ratio test may represent an artefactually low degree of variability. Neurophysiological techniques in current use are characterized by technical limitations and intra-individual variability in patients with established diabetic neuropathy.

Blood Glucose↗