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.

Comparison of post-surgery follow-up methods in patients aged 80 years or older with non-metastatic colorectal cancer

PURPOSE: Studies investigating the appropriate post-surgery follow-up method for elderly patients with colorectal cancer are limited. Thus, the purpose of this study was to compare survival rates between two follow-up methods in patients aged 80 years or older who underwent surgery for colorectal cancer.METHODS: Between January 1, 2002 and December 31, 2010, 165 patients aged 80 years or older underwent curative resection for non-metastatic colorectal cancer at the Department of Surgery, Seoul National University Hospital. Sixty-six of these patients were excluded due to the lack of follow-up, while the remaining 99 were included in our study. These 99 patients were divided into the following two groups depending on their post-surgery follow-up method. Patients who underwent follow-up on a regular basis, which was defined as once every six months to one year, with carcinoembryonic antigen (CEA) and computed tomography (CT) comprised the Regular group, and those who received follow-up with CEA alone or underwent CT procedures once every two years or more comprised the Minimal group. Overall survival was analyzed with the log-rank test and Cox regression analysis.RESULTS: Of the 99 patients, 62 were in Regular group and 37 were in Minimal group. There was no difference in overall survival rate between the two post-surgery follow-up methods (regular group vs. minimal group: 51.6% vs. 50.9% [5-year overall survival rate], P=0.819). Additionally, no significant differences was detected between the groups following multivariate analysis (harzard ratio=0.907; 95% confidence interval=0.460–1.788, P=0.777).CONCLUSION: A significant survival gain was not observed between Regular and Minimal group. To draw a more definite conclusion, a multi-center randomized research study should be conducted.

Development of an Integrated Reporting System for Verifying Hemolysis, Icterus, and Lipemia in Clinical Chemistry Results

BACKGROUND: Hemolysis, icterus, and lipemia (HIL) cause preanalytical interference and vary unpredictably with different analytical equipments and measurement methods. We developed an integrated reporting system for verifying HIL status in order to identify the extent of interference by HIL on clinical chemistry results. METHODS: HIL interference data from 30 chemical analytes were provided by the manufacturers and were used to generate a table of clinically relevant interference values that indicated the extent of bias at specific index values (alert index values). The HIL results generated by the Vista 1500 system (Siemens Healthcare Diagnostics, USA), Advia 2400 system (Siemens Healthcare Diagnostics), and Modular DPE system (Roche Diagnostics, Switzerland) were analyzed and displayed on physicians' personal computers. RESULTS: Analytes 11 and 29 among the 30 chemical analytes were affected by interference due to hemolysis, when measured using the Vista and Modular systems, respectively. The hemolysis alert indices for the Vista and Modular systems were 0.1-25.8% and 0.1-64.7%, respectively. The alert indices for icterus and lipemia were <1.4% and 0.7% in the Vista system and 0.7% and 1.0% in the Modular system, respectively. CONCLUSIONS: The HIL alert index values for chemical analytes varied depending on the chemistry analyzer. This integrated HIL reporting system provides an effective screening tool for verifying specimen quality with regard to HIL and simplifies the laboratory workflow.

Factors Influencing the False Positive Signals of Continuous Monitoring Blood Culture System / 대한임상미생물학회지

BACKGROUND: The false positive signals of a continuous monitoring blood culture system (CMBCS) increase the reporting time and laboratory cost. This study aimed to determine the highly relevant variables that discriminate false positive signals from true positive signals in a CMBCS. METHODS: Among 184,363 blood culture sets (aerobic and anaerobic), the signal-positive samples according to a BACTEC FX system (Plus Aerobic/F, BDA; Plus Anaerobic/F, BDN) and BacT/Alert 3D system (Standard Aerobic, BSA; Standard Anaerobic, BSN) between April 2010 and November 2013 were classified into two groups: false positive or true positive signals. The data of 15 parameters between the two groups were then statistically compared. RESULTS: Among total blood cultures, the positive rates of CMBCS signals according to BDA, BDN, BSA, and BSN were 4.9%, 2.8%, 3.8%, and 3.2%, respectively. The false positive rates of CMBCS signals according to BDA, BDN, BSA, and BSN were 0.6%, 0.1%, 0.1%, and 0.1%, respectively. The blood volume, detection time, time interval between admission and test, C-reactive protein concentration, leukocyte count, delta neutrophil index, and mean peroxidase index showed statistically significant differences between the two groups. CONCLUSION: There were no variables with diagnostic sensitivity and specificity for discriminating the two groups. Therefore, analysis of bacterial growth curves produced by CMBCS is needed for early and effective detection of false positive signals.

Identification System of Nonfermentative Gram Negative Bacilli Using Microplate / 대한임상미생물학회지

BACKGROUND: The accurate and rapid identification (ID) of nonfermentative gram-negative bacilli (NFB) is essential for diagnostic and therapeutic purposes and for epidemiologic studies of hospital infections. Commercial identification systems of NFB are easy to use but too expensive. The aim of the study was to develop a simple system for the identification of NFB species which are frequently isolated from clinical specimens. METHODS: Eighteen biochemical tests used in NFB microplate ID system were pyocyanin in Tech media; pyoverdin in Flo media; glucose fermentation, acid formation from glucose, maltose, lactose, sucrose, and mannitol in oxidation-fermentation media; Nitrate and nitrite reduction in nitrate media; fornithine decarboxylase, lysine decarboxylase, and arginine dihydrolase in Moeller decarboxylase media; acetamide, urease, citrate, 42degrees C growth, and oxidase test. For the establishment of NFB's biochemical data in microplate ID system, 175 consecutive isolates of NFB from clinical specimens isolated during the period of April 2000 were simultaneously tested by microplate method and API 32GN. RESULTS: Ninety-two percent of clinical isolates of NFB were identified to the species level by NFB microplate ID system. CONCLUSIONS: The NFB microplate ID system is simple to use, rapid and economical. Further modification are needed to improve the accuracy and identification rate of NFB isolates.

Microplate Identification System of Enterobacteriaceae / 대한임상미생물학회지

BACKGROUND: To access the accuracy and clinical usefulness of microplate identification (ID) system for the identification of Enterobacteriaceae, we compared microplate ID system with API 20E(bioMerieux, Etoile, France). METHODS: Ninety-two cultures of Enterobacteriaceae and one isolate of Aeromonas species were simultaneously identified by microplate ID system and the API 20E. Twenty biochemical tests used in microplate ID system were lactose, sucrose, and H2S in Kligler's iron agar media; indole, sucrose, raffinose, arabinose, trehalose, adonitol, dulcitol, sorbitol, cellibiose, methy-red, phenylalanine deaminase, ornithine decarboxylase, lysine decarboxylase, arginine dihydrolase, urease, and citrate in microplate; and oxidase test. The identification was obtained by considering percent likelihood(% ID), modal frequency and ID score method. RESULTS: Among the 92 cultures of Enterobacteriaceae and one isolate of Aeromonas species, agreement rate of identification according to the % ID between microplate ID system and API 20E were 90.3% to the species level and 97.8% to the genus level. CONCLUSIONS: For the identification of clinical Enterobacteriaceae isolates, the microplate ID system compares favorably with API 20E in identification accuracy and have the advantage of costsaving and easy to use.

Isolation Rate and Biochemical Reaction of Enterobacteriaceae / 대한임상미생물학회지

BACKGROUND: In clinical microbiology the accurate and rapid identification of members of the family Enterobacteriaceae is essential for diagnostic and therapeutic purposes and for epidemiologic studies. Accuracy of identification system depends mainly on data base such as positive rate of biochemical reactions, relative frequency of occurrence of biotype, and isolation frequency of microorganisms. The purpose of this study was to analyze the isolation rate and biotype frequency of the family Enterobacteriaceae isolated from tertiary care hospital in Korea. METHODS: Isolation frequency of the family Enterobacteriaceae isolated from clinical specimens during the period of January 1998 to June 1998 were analyzed. And biochemical phenotypes of 2,022 isolates tested by 10 tube system consisting of 14 conventional biochemical tests were also analyzed. RESULTS: Isolation rate of the family Enterobacteriaceae to the genus level in order of decreasing frequency were Escherichia (37.0%), Serratia (15.9%), Klebsiella (14.9%), Enterobacter (11.1%), Providencia (8.1%), Citrobacter (2.8%), Proteus (2.5%), Morganella (2.4%), Salmonella (2.4%), and Cedecea (0.7%). Among the genus of the family Enterobacteriaceae, Budvicia, Edwardsiella, Ewingella, Hafnia, Kluyvera, Leminorella, Moellerella, Shigella, Tatumella, Xenorhabdus, Yersinia, and Yokenella were not isolated. The number of species and genus of the family Enterobacteriaceae by this study were 48 and 12, respectively. Over 95% of all clinical isolates belonged to only 25 species. CONCLUSIONS: Although these data about frequency of relative isolation rate and biotype patterns of the family Enterobacteriaceae is inadequate according to species and genus, yet these data will be utilized for the application and development of identification method of the family Enterobacteriaceae.

Development of Interpretative Reporting and Quality Control Program of Disk Susceptibility Test Using Antibiogram / 대한임상병리학회지

BACKGROUND: Some bacteria have typical antibiogram profiles which can be used to verify antimicrobial susceptibility tests and organisms identification. So, we developed interpretative reporting and quality control software program using antibiogram of disk susceptibility test for more accurate results and helping physician's decision making in antibiotic therapy. METHODS: A computer program was developed with knowledge base rules based on antimicrobial disks tested, bacterial classification, bacteria's resistance mechanism and phenotypic probability to antibiogram results. And comment contents according to detection code of antibiogram were coded. All comment code were displayed to computer's screen, and interpreted results were printed to the final report after the validation and correction of the disk susceptibility test results. RESULTS: Detection code for evaluating aminoglycoside susceptibility pattern of gram-negative bacilli were detected, in order of decreasing frequency, Stenotrophomonas maltophilia (9.1%), Citrobacter freundii (9.1%), Enterobacter species (8.3%), Klebsiella pneumoniae (7.6%), Escherichia coli (3.6%), and Acinetobacter species (3.3%). More than 5% of C. freundii, Enterobacter species, E. cloacae, E. aerogenes, and Morganella morganii were detected by detection code for evaluating natural resistance. CONCLUSIONS: It is considered that this program is useful in quality control of antimicrobial susceptibility test and decision making in antimicrobial therapy of patients. And detection rate of rule check codes on natural resistances of gram-negative bacilli in this study were higher than those previously reported. Finally, it is concluded that further studies on natural resistance of antimicrobials about gram-negative bacilli, and the addition and reformation of codes for rule check and comment contents are needed.

Evaluation of 10 Tube System for the Identification of Enterobacteriaceae / 대한임상병리학회지

BACKGROUND: The selection of identification (ID) system of Enterobacteriaceae depends mainly on accuracy of identification system, cost of operation and convenience of testing. Commercial ID kits are easy to use but too expensive. Therefore, we designed a computerized ID system based on 10 tubes which were composed of 14 conventional biochemical tests to identify the Enterobacteriaceae and Vibrionaceae. The purpose of this present study was to assess the clinical usefulness of 10 tube system as an identification system for Enterobacteriaceae in clinical microbiology laboratories. METHODS: During the period of January 1998, 189 Enterobacteriaceae and 2 Aeromonas spp. consecutively isolated from clinical specimens were simultaneously identified by 10 tube system and the API rapid ID 32 E. Fourteen conventional biochemical tests used in 10 tube system were lactose, sucrose, and H2S in Kligler's iron agar media; motility, indole, and ornithine decarboxylase in motility-indole-ornithine decarboxylase agar media; citrate, urease, lysine decarboxylase, phenylalanine deaminase, arginine dihydrolase, arabinose, trehalose, and adonitol. Identification program used in 10 tube system were % ID method and ID score method. RESULTS: Among the 191 isolates, agreement rate of identification between 10 tube system and API rapid ID 32 E were 96.0% to the species level and 99.4% to the genus level. And identification accuracy of 10 tube system was 90.6% to the species level and 93.2% to the genus level. CONCLUSIONS: 10 tube system has been shown to be an accurate, cost-effective alternative to the use of commercial kit systems for identification of Enterobacteriaceae.