Clinical Application of Overlapping Confidence Intervals for Monitoring Changes in Serial Clinical Chemistry Test Results

BACKGROUND: Interpretation of changes in serial laboratory results is necessary for both clinicians and laboratories; however, setting decision limits is not easy. Although the reference change value (RCV) has been widely used for auto-verification, it has limitations in clinical settings. We introduce the concept of overlapping confidence intervals (CIs) to determine whether the changes are statistically significant in clinical chemistry laboratory test results.METHODS: In total, 1,202,096 paired results for 33 analytes routinely tested in our clinical chemistry laboratory were analyzed. The distributions of delta% absolute values and cut-off values for certain percentiles were calculated. The CIs for each analyte were set based on biological variation, and data were analyzed at various confidence levels. Additionally, we analyzed the data using RCVs and compared their clinical utility.RESULTS: Most analytes had low indexes of individuality with large inter-individual variability. The 97.5th percentile cut-offs for each analyte were much larger than conventional RCVs. The percentages of results exceeding RCV(95%) and RCV(99%) corresponded to those with no overlap at the 83.4% and 93.2% confidence levels, respectively.CONCLUSIONS: The use of overlapping CIs in serial clinical chemistry test results can overcome the limitations of existing RCVs and replace them, especially for analytes with large intra-individual variation.

Daily urinary excretion of bisphenol A

<p><b>OBJECTIVES</b>Concerns over dietary exposure to bisphenol A (BPA), an endocrine disruptor, have been raised because BPA is contained in resins and plastics commonly used for the preservation of food and beverages. The purpose of the present study was to assess daily intake levels of BPA in a group of male subjects by measuring total urinary BPA (free BPA plus BPA released by treatment with β-glucuronidase), as well as determining intra-individual variation in BPA excretion.</p><p><b>METHODS</b>Twenty-four-hour urine was collected from 5 subjects for 5 consecutive days for the evaluation of between-day variation in urinary BPA excretion and from 36 male subjects for the estimation of the level of daily BPA intake. BPA in the urine samples was measured by GC/MS/MS following enzymatic hydrolysis of BPA glucuronate, solid phase extraction, and derivatization.</p><p><b>RESULTS</b>A large between-day variation was found over 5 days for the daily excretion of urinary BPA in the 5 subjects. The daily excretion of urinary BPA was distributed log-normally in the 36 male subjects, with the median value being 1.2 μg/day (range: <0.21-14 μg/day), which was far below the Tolerable Daily Intake (0.01 mg/kg bw) recommended by a scientific committee in the European Commission in 2002. However, the maximum estimated intake per body weight (0.2 μg/kg/day) was only one order of magnitude lower than the reported lowest level for reproductive/behavioral effects in pregnant mice (2 μg/kg/day).</p><p><b>CONCLUSIONS</b>Measuring urinary BPA in urine is a suitable approach for estimating short-term BPA intake levels in individuals and/or estimating the average exposure level of populations. Urine analyses will be increasingly important in the human health risk assessment of BPA.</p>

Daily Urinary Excretion of Bisphenol A

Objectives: Concerns over dietary exposure to bisphenol A (BPA), an endocrine disruptor, have been raised because BPA is contained in resins and plastics commonly used for the preservation of food and beverages. The purpose of the present study was to assess daily intake levels of BPA in a group of male subjects by measuring total urinary BPA (free BPA plus BPA released by treatment with β-glucuronidase), as well as determining intra-individual variation in BPA excretion. Methods: Twenty-four-hour urine was collected from 5 subjects for 5 consecutive days for the evaluation of between-day variation in urinary BPA excretion and from 36 male subjects for the estimation of the level of daily BPA intake. BPA in the urine samples was measured by GC/MS/MS following enzymatic hydrolysis of BPA glucuronate, solid phase extraction, and derivatization. Results: A large between-day variation was found over 5 days for the daily excretion of urinary BPA in the 5 subjects. The daily excretion of urinary BPA was distributed log-normally in the 36 male subjects, with the median value being 1.2 μg/day (range: <0.21-14 μg/day), which was far below the Tolerable Daily Intake (0.01 mg/kg bw) recommended by a scientific committee in the European Commission in 2002. However, the maximum estimated intake per body weight (0.2 μg/kg/day) was only one order of magnitude lower than the reported lowest level for reproductive/behavioral effects in pregnant mice (2 μg/kg/day). Conclusions: Measuring urinary BPA in urine is a suitable approach for estimating short-term BPA intake levels in individuals and/or estimating the average exposure level of populations. Urine analyses will be increasingly important in the human health risk assessment of BPA.

Reaction Times in Schizophrenia / 신경정신의학

The reaction time(RT) has been known to reflect attention that controls the flow of information processing. Extensive research has demonstrated cognitive impairment in schizophrenia subjects using RT tasks. However, little work has been done examining the relative contribution of DT(decision time) and MT(motor time) to slowed RT in schizophrenics. Also, recent investigators have observed that schizophrenic patients exhibit larger intra-individual variability in RT than do normal comparison subjects. The purpose of this study, using multi-stimulus convergent RT task, was to explore the speed of RT, relative contribution of decision time(DT) and motor time(MT) to slowed RT, overall sequential profile in 25 repeated-time measurements in 10 schizophrenic out-patients and 10 normal control subjects. Overall reaction time and decision time were slower in schizophrenic subjects than in normal controls. The motor time was not shown to be significantly different between the two groups with 0.05 significance level, although there was some trend indicating schizophrenic subjects were slower consistently in repreated measurements over time. These results suggested that the slower reaction time in schizophrenic subjects was mostly determined by cognitive component, decision time rather than motor time. Sequential profile of repeated measurements showed greater intraindividual and interindividual variations in schizophrenics than in normal controls. These results indicate that high variabilities are not merely measurement errors but characteristic of schizophrenic psychopathology.