Schemes and Performance Evaluation Criteria of Korean Association of External Quality Assessment (KEQAS) for Improving Laboratory Testing

External quality assessment (EQA) is important for evaluating clinical laboratories and enhancing their testing quality. EQA schemes are variable; thus, it is crucial that the EQA organizers share their experiences to continuously improve the EQA scheme. The Korean Association of External Quality Assessment Service (KEQAS) has been the leading, authorized EQA institute for the standardization and quality management of laboratory testing in Korean medical institutions since 1976. The EQA scheme underwent a major change in 2016, and the number of EQA programs increased significantly since then. The key changes implemented in EQA scheme include a fully computerized assessment to accelerate feedback and unification of the testing and reporting methods. We provide an overview of the EQA schemes and performance evaluation criteria of the KEQAS and suggest directions for achieving the global harmonization of EQA.

Standardization Status of Total Cholesterol Concentration Measurement: Analysis of Korean External Quality Assessment Data

Background@#Total cholesterol concentration measurement is important in the diagnosis of dyslipidemia and evaluation of cardiovascular disease risk factors. Measurement reliability for obtaining an accurate total cholesterol concentration requires procedure standardization. We evaluated the standardization status for total cholesterol concentration measurement through Korean external quality assessment (EQA) data analysis. @*Methods@#This study involved 1,670 laboratories that participated in the EQA of total cholesterol concentration measurements in 2019 for 32 products from different manufacturers. The target concentrations of three quality control (QC) materials (samples A, B, and C) were measured using the reference method and compared with EQA data. The performance criteria for total cholesterol concentration measurement were based on the National Cholesterol Education Program guidelines, with ± 3% inaccuracy. @*Results@#The target values and inaccuracies of the QC material based on the reference method measurements were 254.65 ± 7.64, 108.30 ± 3.25, and 256.29 ± 7.69 mg/dL (6.59 ± 0.20, 2.80 ± 0.08, and 6.63 ± 0.20 mmol/L) for samples A, B, and C, respectively.The performance criteria were not met in 42.7% laboratories for sample A, 68.4% of laboratories for sample B, and 38.0% laboratories for sample C. @*Conclusions@#Despite significant efforts to accurately measure total cholesterol concentrations, further actions are needed for measurement standardization. Manufacturers reporting values that differ from target values should check calibrator traceability; additional efforts to accurately measure total cholesterol concentrations are required for laboratories that use products from these manufacturers.

Turnaround Time (TAT) Setting Status of 30 Domestic Clinical Laboratories and Consideration for Improvement and Management of TAT

Background@#Turnaround time (TAT) is a major quality control indicator and can be defined differently depending on the starting point in the examination process. To determine effective TAT management plan, we investigated the status of TAT management in clinical laboratories in Korea. @*Methods@#A questionnaire was developed using Google web pages and a questionnaire survey was conducted at 30 clinical laboratories in laboratory medicine from September 1 to 11 in 2018. Questions were developed regarding management time, starting point standards, management goals, most problematic stages of delayed TAT, clinical measures, and shortening barriers for investigation. @*Results@#All clinical laboratories requested to undertake the survey completed the questionnaire (response rate 100%, 30/30) and answered that they were setting and managing TAT for all tests. Many laboratories (33%) set the TAT starting point as the reception stage, prior to commencing centrifugation. Of the surveyed laboratories, 37% achieved a TAT of 120 min or more for general tests, 27% met the TAT of 90 min for pre-clinic tests, and 77% met the TAT of 60 min for completion of stat tests. Most laboratories (67%) reported that the most delayed stage was pre-analysis, and 50% reported that the greatest obstacle to shortening TAT was the ratio of stat and pre-clinic tests to general tests. @*Conclusions@#The laboratories participating in this survey set a TAT based on various criteria and were performing management for TAT improvement. The results of this study can be used as basic data to guide efficient TAT management.

Effects of the new diagnosis-related group-based payment system and the increased incentive policy rates on the utilization rate of diagnostic laboratory test in Korea

A new diagnosis-related group (DRG) based payment system has been implemented in most public hospitals in Korea. We investigated the effects of the new DRG system and its incentive policy on the utilization rate of diagnostic laboratory tests. Three groups were categorized; 36 hospitals under the new DRG system (participant group), 72 hospitals (control-1) matching with 36 participants according to the number of beds, and 42 tertiary hospitals (control-2). The patients of acute myocardial infarction, cerebral infarction, type 2 diabetes mellitus, and gonarthrosis receiving total arthroplasty were included. We analyzed the mean length of stay and the number of diagnostic laboratory tests conducted during hospitalization of the three groups according to the new DRG system and the incentive policy rates under the new DRG system. Before participating in the new DRG system, the number of diagnostic laboratory tests in the participant group was less than that in the two control groups for all four diseases. However, although the participant group’s length of stay decreased under the new DRG system, the number of diagnostic laboratory tests increased as the maximum incentive policy rate increased. The increment of the number of diagnostic laboratory tests was prominent in the period of a maximum of 35% incentive policy rates. Finally, the number of diagnostic laboratory tests of the participant group was similar to or exceeded that of the control-2 group. The new DRG system’s incentive policy rates played a driving force on the increased utilization rate of the diagnostic laboratory test. For preparing in advance for the change in incentive policy rates, monitoring and guidelines for the utilization of diagnostic laboratory tests are necessary.

Turnaround Time (TAT) Setting Status of 30 Domestic Clinical Laboratories and Consideration for Improvement and Management of TAT

Background@#Turnaround time (TAT) is a major quality control indicator and can be defined differently depending on the starting point in the examination process. To determine effective TAT management plan, we investigated the status of TAT management in clinical laboratories in Korea. @*Methods@#A questionnaire was developed using Google web pages and a questionnaire survey was conducted at 30 clinical laboratories in laboratory medicine from September 1 to 11 in 2018. Questions were developed regarding management time, starting point standards, management goals, most problematic stages of delayed TAT, clinical measures, and shortening barriers for investigation. @*Results@#All clinical laboratories requested to undertake the survey completed the questionnaire (response rate 100%, 30/30) and answered that they were setting and managing TAT for all tests. Many laboratories (33%) set the TAT starting point as the reception stage, prior to commencing centrifugation. Of the surveyed laboratories, 37% achieved a TAT of 120 min or more for general tests, 27% met the TAT of 90 min for pre-clinic tests, and 77% met the TAT of 60 min for completion of stat tests. Most laboratories (67%) reported that the most delayed stage was pre-analysis, and 50% reported that the greatest obstacle to shortening TAT was the ratio of stat and pre-clinic tests to general tests. @*Conclusions@#The laboratories participating in this survey set a TAT based on various criteria and were performing management for TAT improvement. The results of this study can be used as basic data to guide efficient TAT management.

Effect of Having a Usual Source of Care on Medical Expenses – Using the Korea Health Panel Data

BACKGROUND: There is a controversy about the effect of having a usual source of care on medical expenses. Although many studies have shown lower medical expenses in a group with a usual source of care, some have shown higher medical expenses in such a group. This study aimed to empirically demonstrate the effect of having a usual source of care on medical expenses. METHODS: The participants included those aged 20 years and older who responded to the questionnaire about “having a usual source of care” from the Korean Health Panel Data of 2012, 2013, and 2016 (6,120; 6,593; and 7,598 respectively). Those who responded with “I do not get sick easily” or “I rarely visit medical institutions” as the reasons for not having a usual source of care were excluded. The panel regression with random effects model was performed to analyze the effect of having a usual source of care on medical expenses. RESULTS: The group having a usual source of care spent 20% less on inpatient expenses and 25% less on clinic expenses than the group without a usual source of care. Particularly, the group having a clinic-level usual source of care spent 12% less on total medical expenses, 9% less on outpatient expenses, 35% less on inpatient expenses, and 74% less on hospital expenses, but 29% more on clinic expenses than the group without a usual source of care. CONCLUSION: This study confirmed that medical expenses decreased in the group with a usual source of care, especially a clinic-level usual source of care (USC), than in the group without a usual source of care. Encouraging people to have a clinic-level USC can control excessive medical expenses and induce desirable medical care utilization.

Renoprotective effects of febuxostat compared with allopurinol in patients with hyperuricemia: A systematic review and meta-analysis

BACKGROUND: Hyperuricemia is reported to be related to rapid progression of renal function in patients with chronic kidney disease (CKD). Allopurinol, a uric acid lowering agent, protects renal progression. However, it is not widely used in patients with CKD because of its serious adverse event. Febuxostat can be alternatively used for patients who are intolerable to allopurinol. We aimed to determine renoprotective effect and urate-lowering effect between the two drugs. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials to assess the effects of febuxostat compared to allopurinol in patients with hyperuricemia. MEDLINE, Embase, and Cochrane Library databases were searched to identify research publications. RESULTS: Four relevant publications were selected from among 3,815 studies. No significant differences were found in the changes in serum creatinine from baseline between the febuxostat and allopurinol groups. Changes in estimated glomerular filtration rate (eGFR) were observed between the two groups at 1 month (mean difference 1.65 mL/min/1.73 m², 95% confidence interval [CI] 0.38, 2.91 mL/min/1.73 m²; heterogeneity χ² = 1.25, I² = 0%, P = 0.01); however, the changes in eGFR were not significantly different at 3 months. A significant difference did exist in the changes in albuminuria levels from baseline between the febuxostat and allopurinol groups (mean difference −80.47 mg/gCr, 95% CI −149.29, −11.64 mg/gCr; heterogeneity χ² = 0.81, I² = 0%, P = 0.02). A significant difference was also observed in the changes in serum uric acid from baseline between the febuxostat and allopurinol groups (mean difference −0.92 mg/dL, 95% CI −1.29, −0.56 mg/dL; heterogeneity χ² = 6.24, I² = 52%, P < 0.001). CONCLUSION: Febuxostat might be more renoprotective than allopurinol.

Predictive Value of Dental Maturity for a Positive Gonadotropin-Releasing Hormone Stimulation Test Result in Girls with Precocious Puberty

Dental maturity is associated with skeletal maturity, which is advanced in girls with central precocious puberty (CPP). We investigated the performance of dental maturity as a screening method for CPP using mandibular second premolar and molar calcification stages, assessed the associated anthropometric and laboratory factors, and evaluated pubertal response predictors using the gonadotropin-releasing hormone stimulation test (GnRHST) in prepubertal and pubertal girls. A prospective case-control study was conducted in girls, aged 7.0–8.9 years, classified into pubertal (peak luteinizing hormone [LH] after GnRHST ≥ 5 IU/L), prepubertal (peak LH < 5 IU/L), and control groups. Auxological and biochemical tests, panoramic radiographs, and GnRHSTs in participants with breast development were conducted. Dental maturity was assessed using the Demirjian index (DI). We included 103 girls (pubertal, 40; prepubertal, 19; control, 44). Chronological age (CA) was not significantly different between groups. Bone age (BA) and BA advancement was higher in the pubertal and prepubertal groups. Increased DI values at the mandibular second premolar and molar were significantly associated with CA, BA, BA advancement, height standard deviation score (SDS), peak LH after GnRHST, and insulin-like growth factor-I (IGF-I) (all P < 0.05). Moreover, odds ratio (OR) of the mandibular second premolar and molar (a DI value of ≥ E) for predicting a positive response to GnRHST was 8.7 (95% confidence intervals [CI], 2.9–26.1) and 5.2 (95% CI, 2.2–12.7), respectively. Dental maturity was a strong predictor for diagnosing CPP. Determining dental maturity in girls with suspected precocious puberty might help determine the performance of GnRHSTs.

Report on the Project for Establishment of the Standardized Korean Laboratory Terminology Database, 2015

The National Health Information Standards Committee was established in 2004 in Korea. The practical subcommittee for laboratory test terminology was placed in charge of standardizing laboratory medicine terminology in Korean. We aimed to establish a standardized Korean laboratory terminology database, Korea-Logical Observation Identifier Names and Codes (K-LOINC) based on former products sponsored by this committee. The primary product was revised based on the opinions of specialists. Next, we mapped the electronic data interchange (EDI) codes that were revised in 2014, to the corresponding K-LOINC. We established a database of synonyms, including the laboratory codes of three reference laboratories and four tertiary hospitals in Korea. Furthermore, we supplemented the clinical microbiology section of K-LOINC using an alternative mapping strategy. We investigated other systems that utilize laboratory codes in order to investigate the compatibility of K-LOINC with statistical standards for a number of tests. A total of 48,990 laboratory codes were adopted (21,539 new and 16,330 revised). All of the LOINC synonyms were translated into Korean, and 39,347 Korean synonyms were added. Moreover, 21,773 synonyms were added from reference laboratories and tertiary hospitals. Alternative strategies were established for mapping within the microbiology domain. When we applied these to a smaller hospital, the mapping rate was successfully increased. Finally, we confirmed K-LOINC compatibility with other statistical standards, including a newly proposed EDI code system. This project successfully established an up-to-date standardized Korean laboratory terminology database, as well as an updated EDI mapping to facilitate the introduction of standard terminology into institutions.

Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.

Bacteremia Caused by Eggerthella lenta in an Elderly Patient with an Intra-abdominal Abscess

Eggerthella lenta is an anaerobic, non-spore-forming, non-motile, gram-positive bacillus that can be isolated from human feces and a few other clinical specimens. Bacteremia caused by the organism is rare but, when present, is always of clinical significance. E. lenta is an emerging pathogen that has been under-recognized because of difficulties with its laboratory identification. Few reports on E. lenta infections and the optimal treatment thereof are available. We describe a case of bacteremia caused by E. lenta in an elderly patient with an intra-abdominal abscess. We also review the current literature.

Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines Part 2

Pharmacogenetics is a rapidly evolving field and the number of pharmacogenetic tests for clinical use is steadily increasing. However, incorrect or inadequate implementation of pharmacogenetic tests in clinical practice may result in a rise in medical costs and adverse outcomes in patients. This document suggests guidelines for the clinical application, interpretation, and reporting of pharmacogenetic test results based on a literature review and the collection of evidence-based expert opinions. The clinical laboratory practice guidelines encompass the clinical pharmacogenetic tests covered by public medical insurance in Korea. Technical, ethical, and regulatory issues related to clinical pharmacogenetic tests have also been addressed. In particular, this document comprises the following pharmacogenetic tests: CYP2C9 and VKORC1 for warfarin, CYP2C19 for clopidogrel, CYP2D6 for tricyclic antidepressants, codeine, tamoxifen, and atomoxetine, NAT2 for isoniazid, UGT1A1 for irinotecan, TPMT for thiopurines, EGFR for tyrosine kinase inhibitors, ERBB2 (HER2) for erb-b2 receptor tyrosine kinase 2-targeted therapy, and KRAS for anti-epidermal growth factor receptor drugs. These guidelines would help improve the usefulness of pharmacogenetic tests in routine clinical settings.

A Survey on the Awareness and Usage of the National Transfusion Guideline in Korea / 대한수혈학회지

BACKGROUND: Transfusion guidelines play an important role for the appropriate use and quality assurance of blood and transfusion services. The Korean national transfusion guideline was developed in 2009 and went under full amendment in 2016. The purpose of this study was to investigate the awareness and practicality of the transfusion guideline in Korea. METHODS: Questionnaires about the Korean national transfusion guideline were sent by traditional mail or e-mail to a total of 1,179 clinicians, 32 academic societies, and 6 institutions. RESULTS: Three hundred and seventy-four answers were received; a response rate of 30.7%. The proportion of respondents with good awareness of the guideline was 23.3%, which is a significant increase compared with 10.9% in 2008. Respondents with good awareness were more dependent on the transfusion guideline when making transfusion decisions. CONCLUSION: There was a considerable increase in the awareness of the national transfusion guideline in Korea.

Comparison of the Ability of Multiplex and Singleplex PCR to Detect Human Respiratory Viruses

BACKGROUND: The use of the multiplex polymerase chain reaction (PCR) technique for respiratory viruses has become popular in Korea owing to its convenience and sensitivity. However, concerns remain with regard to possible interference due to multiplexing. METHODS: We compared the analytical sensitivity and virus interference of a commercially available, multiplex PCR kit (AdvanSure Respiratory virus real-time PCR kit, LG Life Sciences, Korea) with that of singleplex PCR to detect 11 viruses including coronavirus 229E and OC43; parainfluenza virus 1 (PIV 1), parainfluenza virus 2 (PIV 2), and parainfluenza virus 3 (PIV 3); influenza virus A (INF A) and influenza virus B (INF B); respiratory syncytial virus A (RSV A) and respiratory syncytial virus B (RSV B); adenovirus; and rhinovirus A, B, and C. RESULTS: The lowest detected viral concentrations of coronavirus 229E and OC43, INF A and B, RSV A and B, adenovirus, and rhinovirus A, B, and C were the same for both, multiplex and singleplex systems. However, the lowest detected viral concentrations of PIV1, 2, and 3 differed by 1 dilution factor between the two systems. Threshold cycle (Ct) values for mixed viruses within the same well were not significantly influenced by each other, where the difference between Ct values ranged from 0.24 to 1.99. CONCLUSIONS: Analytical sensitivity of multiplex PCR was comparable to that of singleplex PCR for respiratory viruses. No significant interference was observed with mixed virus samples using multiplexed PCR.

Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines Part 1

Pharmacogenetics is a rapidly evolving field, and the number of pharmacogenetic tests for clinical use is steadily increasing. However, incorrect or inadequate implementation and use of pharmacogenetic testing in clinical practice may result in an increase in medical costs and adverse patient outcomes. This document contains suggested pharmacogenetic testing guidelines for clinical application, interpretation, and reporting of the results through a literature review and evidence-based expert opinions. The clinical laboratory practice guideline includes clinical pharmacogenetic testing covered by public medical insurance in Korea. Technical, ethical, and regulatory issues related to clinical pharmacogenetic testing are also addressed. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.

False-Positive Elevation of Creatine Kinase MB Mass Concentrations Caused by Macromolecules in a Patient who Underwent Nephrectomy for Renal Cell Carcinoma

No abstract available.

Presence of Differentiating Neuroblasts in Bone Marrow is a Favorable Prognostic Factor for Bone Marrow Metastatic Neuroblastoma at Diagnosis

BACKGROUND: The prognostic impact of the presence of differentiating neuroblasts in bone marrow (BM) remains unclear in BM metastatic neuroblastoma (NB). We aimed to identify the prognostic impact of differentiating neuroblasts in BM at diagnosis and after chemotherapy. METHODS: A total of 51 patients diagnosed with BM metastatic NB at Asan Medical Center between January 1990 and July 2005 were enrolled. BM histology and laboratory data along with overall survival (OS) were compared with regard to the differentiation status of neuroblasts in BM at diagnosis and after chemotherapy. RESULTS: Among the 51 patients, 13 (25.5%) exhibited differentiating neuroblasts in BM at diagnosis and 17/51 (33.3%) exhibited them after chemotherapy. The only significant difference among patient groups was the improved OS in patients with differentiated neuroblasts in BM at diagnosis (P=0.021). In contrast, the differentiation status of neuroblasts in BM after chemotherapy did not affect OS (P=0.852). CONCLUSIONS: Our study is the first report describing the presence of differentiating neuroblasts in BM. The presence of differentiating neuroblasts in BM at diagnosis may be a favorable prognostic factor for patients with BM metastatic NB; however, the same phenomenon after chemotherapy is irrelevant to prognosis.

Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls?

PURPOSE: A gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP). The aim of this study was to investigate the diagnostic accuracy of basal gonadotropin levels for girls with suspected precocious puberty and to evaluate the factors affecting positive results of the GnRHST. METHODS: Korean girls with early pubertal development who visited the clinic during 2010-2012 were included. Auxological and biochemical tests were evaluated and a standard GnRHST was performed. A peak luteinizing hormone (LH) level of > or =5 IU/L was considered a positive response during the GnRHST. RESULTS: A total of 336 girls were included. The positive responses were observed in 241 girls (71.7%), and negative responses were found in 95 girls (28.3%). In the logistic regression analysis, the coefficient of the basal LH and basal LH/follicular stimulating hormone (FSH) ratio was 4.23 (P<0.001) and 21.28 (P<0.001), respectively. Receiver operating characteristic analysis showed that the basal LH/FSH ratio is a better predictor of the pubertal result after the GnRHST than the basal LH (area under the curve was 0.745 and 0.740, respectively; P=0.027). Among 189 girls with a basal LH of <0.1 IU/L, 105 (55.6%) had positive responses. CONCLUSION: An elevated level of the basal LH and basal LH/FSH ratio was a significant predicting factor of positive responses during the GnRHST. However a GnRHST was still necessary for diagnostic confirmation of CPP because more than half of the girls with a basal LH level below the detection limit revealed to have CPP.

Evaluation of Plasma Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Tubular Damage in Diabetic Nephropathy / 임상검사와정도관리

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has recently been introduced as a renal biomarker and an increase in its level suggests tubular injury. Diabetic nephropathy, a leading cause of end-stage renal disease, causes typical changes characterized by glomerulosclerosis and eventual tubular damage in the kidney. In the present study, we attempted to validate the usefulness of plasma NGAL (pNGAL) as a biomarker for tubular damage in diabetic nephropathy. METHODS: The plasma NGAL levels of 260 diabetes mellitus patients and 50 healthy individuals werewas measured by means of fluorescent immunoassay using with the Triage NGAL test (Biosite, USA). The patients were divided into 3 groups on the basis of their urinary albumin excretion (UAE) levels, and the pNGAL differences among each group were analyzed. The degree of albuminuria and cystatin C-based glomerular filtration rate (GFR) were also compared with the pNGAL levels. RESULTS: The mean pNGAL levels of the normal subjects and diabetic patients were 61.9 +/- 4.81 ng/mL and 93.4 +/- 71.78 ng/mL, respectively. pNGAL level was significantly increased in patients with severe albuminuria (P < 0.001). The pNGAL level was found to be positively correlated with the degree of albuminuria (R2 = 0.218, P < 0.001) and inversely correlated with GFR (R2 = 0.269, P < 0.001). Particularly, the pNGAL level of patients with diabetic nephropathy was found to be associated with the renal damage and independent of other factors influencing the renal damage (R2 = 0.218). CONCLUSIONS: pNGAL level independently reflects renal damage in patients with diabetic nephropathy. Measurement of pNGAL level combined with UAE would help enable to detect both glomerular and tubular damage in diabetic nephropathy patients.

Comparison of Sputum and Nasopharyngeal Aspirates for Molecular Detection of Community-Acquired Pneumonia Pathogens / 임상검사와정도관리

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of infectious diseases and mortality. CAP is primarily treated by administration of adequate antibiotics against the causative pathogens. Because detection of some pathogens by the conventional culture method is difficult, the use of molecular diagnostic methods is increasing. Although an optimal specimen type is very important for proper testing, there is no consensus on the optimal specimen type for detecting CAP pathogens. In this study, we compared sputum specimens and nasopharyngeal aspirates (NPAs) for molecular detection of 4 CAP-causing bacterial species. METHODS: From September 2011 to January 2012, we collected sputum specimens and NPAs from CAP patients on the first or second day of hospitalization. The specimens were tested for Mycoplasma pneumoniae, Streptococcus pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila by using commercial real-time PCR. RESULTS: We collected 63 sputum specimens and 96 NPAs from 109 patients and found positive results for 38.1% (24/63) and 28.1% (27/96), respectively (P = 0.251). There were no significant differences in the positive rates obtained for sputum specimens of different quality. CONCLUSIONS: The results obtained using NPAs and sputum specimens for the molecular detection of CAP pathogens were comparable.