Korean Clinical Practice Guidelines: Current Status of Adherence to the RIGHT Checklist

Background@#The Korean Academy of Medical Sciences (KAMS) has been utilizing AGREE II to audit the quality of clinical practice guidelines (CPGs) developed in Korea. Monitoring the RIGHT Checklist adherence could help monitor the quality status and discover areas for improvement of CPG development. @*Methods@#We included 129 CPGs from the past 5 years and assessed each item of the RIGHT Checklist. STATA version 15.0 was used for statistical analysis. @*Results@#Among the seven sections of the RIGHT checklist, sections with a full compliance rate over 60% were ‘basic information’ (65%) and ‘background’ (66%). The other sections’ mean full compliance rates were ‘Evidence’ 52%, ‘Recommendation’ 35%, ‘Review and quality assurance’ 25% and ‘Funding, declaration and management of interest’ 17%. Sections with a partial compliance rate over 60% were ‘Recommendation’ (60%) and ‘Funding, declaration and management of interest’ (70%). Non-compliance was highest in the ‘Review and quality assurance’ (17%) domain. In comparison between groups 1 (under median group) and 2 (over median group), group 2 showed a tendency to have multi-stakeholder involvement and present sufficient information on financial resources and conflict of interest declarations. For the CPGs developmental methodology aspect, group 2 provided more pertinent information than group 1 about supporting evidence-making and the process from evidence to recommendation. @*Conclusion@#This study evaluated adherence to the RIGHT Checklist of CPGs developed in Korea. It can provide helpful information to develop strategic plans for enhancing the capabilities of developing CPGs in Korea.

Adverse Events Associated with the Use of Leukocyte Reduction Filters and Blood Transfusion Sets: Experience of a Single Institute in Korea and Status of Adverse Event Reporting in Korea and the United States / 대한수혈학회지

Background@#Leukocyte reduction filters (LRF) and blood transfusion sets (BTS) are frequently used medical devices to prevent blood transfusion-related adverse reactions. This study attempted to analyze these medical devices related adverse events reported by an institution for 10 years and to understand the status of such reports in Korea and the United States (U.S.). @*Methods@#From January 2013 to October 2022, adverse events reported at Soonchunhyang university Bucheon hospital (SCHBC) were analyzed. From 2016 to 2022, adverse events registered in the Korean Medical Device Information Portal and the Total Product Life Cycle (TPLC) database of the U.S. were collected and evaluated using the International Medical Device Regulators Forum (IMDRF) code for medical device problems, clinical signs, and symptoms or conditions. @*Results@#A total of 12, 47, and 1,422 events were identified in SCHBC, Korea, and the U.S., respectively. The medical device problems reported in BTS included fluid leakage, breakage, disconnection, and no flow. In LRF, device or reagent problems, coagulation of device or device components, and filtration problems were reported. Most of the clinical signs and symptoms or conditions were not applicable (98.1%, 1,453/1,481), but hypotension and hemolysis were reported in LRF. @*Conclusion@#To improve the safety of transfusion-related medical devices such as LRF and BTS, proper attention needs to be paid to adverse events and all medical institutions should participate in the reporting of such events.The various adverse events and associated IMDRF codes included in this study would help enable reporting of adverse events and improve patient safety.

Reporting Quality of Diagnostic Accuracy Studies in Laboratory Medicine: Adherence to Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015

BACKGROUND: Poor reporting quality in diagnostic accuracy studies hampers an adequate judgment of the validity of the study. The Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was published to improve the reporting quality of diagnostic accuracy studies. This study aimed to evaluate the adherence of diagnostic accuracy studies published in Annals of Laboratory Medicine (ALM) to STARD 2015 and to identify directions for improvement in the reporting quality of these studies.METHODS: Two independent authors assessed articles published in ALM between 2012–2018 for compliance with 30 STARD 2015 checklist items to identify all eligible diagnostic accuracy studies published during this period. We included 66 diagnostic accuracy studies. A total of the fulfilled STARD items were calculated, and adherence was analyzed on an individual-item basis.RESULTS: The overall mean±SD number of STARD items reported for the included studies was 11.2±2.7. Only five (7.6%) studies adhered to more than 50% of the 30 items. No study satisfied more than 80% of the items. Large variability in adherence to reporting standards was detected across items, ranging from 0% to 100%.CONCLUSIONS: Adherence to STARD 2015 is suboptimal among diagnostic accuracy studies published in ALM. Our study emphasizes the necessity of adherence to STARD to improve the reporting quality of future diagnostic accuracy studies to be published in ALM.

Differences in Perspectives of Medical Device Adverse Events: Observational Results in Training Program Using Virtual Cases

BACKGROUND: Medical device adverse event reporting is an essential activity for mitigating device-related risks. Reporting of adverse events can be done by anyone like healthcare workers, patients, and others. However, for an individual to determine the reporting, he or she should recognize the current situation as an adverse event. The objective of this report is to share observed individual differences in the perception of a medical device adverse event, which may affect the judgment and the reporting of adverse events. METHODS: We trained twenty-three participants from twelve Asia-Pacific Economic Cooperation (APEC) member economies about international guidelines for medical device vigilance. We developed and used six virtual cases and six questions. We divided participants into six groups and compared their opinions. We also surveyed the country's opinion to investigate the beginning point of ‘patient use’. The phases of ‘patient use’ are divided into: 1) inspecting, 2) preparing, and 3) applying medical device. RESULTS: As for the question on the beginning point of ‘patient use,’ 28.6%, 35.7%, and 35.7% of participants provided answers regarding the first, second, and third phases, respectively. In training for applying international guidelines to virtual cases, only one of the six questions reached a consensus between the two groups in all six virtual cases. For the other five questions, different judgments were given in at least two groups. CONCLUSION: From training courses using virtual cases, we found that there was no consensus on ‘patient use’ point of view of medical devices. There was a significant difference in applying definitions of adverse events written in guidelines regarding the medical device associated incidents. Our results point out that international harmonization effort is needed not only to harmonize differences in regulations between countries but also to overcome diversity in perspectives existing at the site of medical device use.

Dose Estimation Curves Following In Vitro X-ray Irradiation Using Blood From Four Healthy Korean Individuals

Cytogenetic dosimetry is useful for evaluating the absorbed dose of ionizing radiation based on analysis of radiation-induced chromosomal aberrations. We created two types of in vitro dose-response calibration curves for dicentric chromosomes (DC) and translocations (TR) induced by X-ray irradiation, using an electron linear accelerator, which is the most frequently used medical device in radiotherapy. We irradiated samples from four healthy Korean individuals and compared the resultant curves between individuals. Aberration yields were studied in a total of 31,800 and 31,725 metaphases for DC and TR, respectively, obtained from 11 X-ray irradiation dose-points (0, 0.05, 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 5 Gy). The dose-response relationship followed a linear-quadratic equation, Y=C+αD+βD², with the coefficients C=0.0011 for DC and 0.0015 for TR, α=0.0119 for DC and 0.0048 for TR, and β=0.0617 for DC and 0.0237 for TR. Correlation coefficients between irradiation doses and chromosomal aberrations were 0.971 for DC and 0.6 for TR, indicating a very strong and a moderate correlation, respectively. This is the first study implementing cytogenetic dosimetry following exposure to ionizing X-radiation.

Correspondence: Response to “Evaluating the Cumulative Impact of Ionizing Radiation Exposure With Diagnostic Genetics”

No abstract available.

Advanced medical devices and regulatory innovations in new health technology assessments

Advances in technology lead to advances in medical devices, and these advances have the positive effect of creating opportunities for beneficial developments in healthcare, such as innovating traditional healthcare processes or expanding opportunities for diagnosing and treating diseases. Nonetheless, device developers, suppliers, users, insurers, and patients all face the challenge of balancing patient safety and health effectiveness with a reasonable profit. In Korea, the New Health Technology Assessment system aims to introduce safe and effective health technology, but this is only effective for the entry of devices onto the healthcare market. This system is not enough for creating a healthy ecosystem in which high-quality technologies and devices survive in the market and naturally exit from the market if not successful. The nation must not lag in the rapid development of medical devices, but the concomitant requirement for patient safety is like two rabbits moving in different directions. There is not enough time to resolve each source of uncertainty for both developers and users. The early adoption of health technologies, including medical devices, offers new opportunities for treatment and diagnosis, but also poses unexpected health risks. Thus, we need to design a plan to generate scientific evidence related to medical devices after they introduced into practice. Additionally, regarding the use of individual medical devices, we believe that the creation of a healthy ecosystem for medical devices by implementing medical device surveillance culture is a way to manage the opportunities and risks of the early introduction of innovative medical devices.

Effect of the Standardization of Diagnostic Tests on the Prevalence of Diabetes Mellitus and Impaired Fasting Glucose

BACKGROUND: Without standardization of medical laboratory's testing practices, there is an increase in false diagnoses when relying on test results. However, the effect of test standardization is difficult to assess numerically. This study's purpose is to quantify the effect of the standardization level of a laboratory on the prevalence of diabetes mellitus (DM) and impaired fasting glucose (IFG). METHODS: Laboratories were classified into three levels: ‘highly-standardized laboratory,’‘basically-standardized laboratory,’ and ‘non-standardized laboratory.’ Based on the results of Korean External Quality Assessment Scheme (KEQAS), the cutoff values for diagnosis of DM and IFG were recalculated, given false positive and false negative rates. RESULTS: The prevalence of DM and IFG in the population as a whole was estimated using the 2013 Korea National Health and Nutrition Examination Survey (KNHANES) database. When the prevalence of DM from KNHANES was 11.88% (95% confidence interval [CI], 10.59%–13.17%), the proportion with a systematic false error ranged from 10.91% (95% CI, 9.65%–12.17%) to 13.09% (95% CI, 11.74%–14.45%). The prevalence of IFG varied from 13.59% (95% CI, 12.25%–14.91%) to 40.49% (95% CI, 38.54%–42.43%), in contrast to 24.58% (95% CI, 22.85%–26.31%) of the reference value. The prevalence of DM and IFG tended to be over- and under-estimated more as the laboratory standardization level became lower, respectively. CONCLUSION: Our study proved that standardization of clinical laboratory tests is an important factor affecting the prevalence estimation of national disease statistics based on the simulation using KNHANES data.

Effect of Accreditation on the Accuracy of Diagnostic Hematologic Tests: Standard Deviation Index Analysis

No abstract available.

Budget Impact of the Accreditation Program for Clinical Laboratories on Colorectal Cancer Screening via Fecal Immunochemical Testing: Results from the National Cancer Screening Program in Korea

BACKGROUND: False-positive fecal immunochemical test (FIT) results in the National Cancer Screening Program (NCSP) for colorectal cancer may lead to unnecessary procedures, such as colonoscopies, increasing the medical costs. We estimated reductions in the cost of National Health Insurance according to the accreditation status of screening facilities participating in the NCSP for colorectal cancer. METHODS: We used data collected between 2007 and 2010 from NCSP and the Korea Central Cancer Registry to identify patients with colorectal cancer. We also ascertained the history of the accreditation of each facility by the Korean Laboratory Accreditation Program (KLAP). Budget impact was defined as a reduction in medical costs achieved when the false-positive rate of the non-accredited facilities decreased relative to that of the accredited facilities. RESULTS: A total of 3,285 screening facilities participated in the NCSP. Of these, 196 were accredited by the KLAP. The false-positive rate of the accredited facilities was 2.47%, and that of the non-accredited facilities was 6.83%. Medical costs were estimated to be reduced by approximately 19 million US dollars (USD), and the cost of detecting one case of colorectal cancer was estimated to decrease from 9,212 USD to 7,332 USD if the false-positive rate of non-accredited facilities were decreased to that of the accredited facilities. Clinics were estimated to have the largest associated cost reduction. CONCLUSIONS: Quality assurance in clinical laboratories could lower false-positive rates and prevent the use of unnecessary procedures, ensuring patient safety and increasing the cost-effectiveness of FIT screening in the NCSP for colorectal cancer.

Advanced medical devices and regulatory innovations in new health technology assessments

Advances in technology lead to advances in medical devices, and these advances have the positive effect of creating opportunities for beneficial developments in healthcare, such as innovating traditional healthcare processes or expanding opportunities for diagnosing and treating diseases. Nonetheless, device developers, suppliers, users, insurers, and patients all face the challenge of balancing patient safety and health effectiveness with a reasonable profit. In Korea, the New Health Technology Assessment system aims to introduce safe and effective health technology, but this is only effective for the entry of devices onto the healthcare market. This system is not enough for creating a healthy ecosystem in which high-quality technologies and devices survive in the market and naturally exit from the market if not successful. The nation must not lag in the rapid development of medical devices, but the concomitant requirement for patient safety is like two rabbits moving in different directions. There is not enough time to resolve each source of uncertainty for both developers and users. The early adoption of health technologies, including medical devices, offers new opportunities for treatment and diagnosis, but also poses unexpected health risks. Thus, we need to design a plan to generate scientific evidence related to medical devices after they introduced into practice. Additionally, regarding the use of individual medical devices, we believe that the creation of a healthy ecosystem for medical devices by implementing medical device surveillance culture is a way to manage the opportunities and risks of the early introduction of innovative medical devices.

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.

A Case of Chronic Myeloid Leukemia With Rare Variant ETV6/ABL1 Rearrangement

No abstract available.

Effect of Accreditation on Accuracy of Diagnostic Tests in Medical Laboratories

BACKGROUND: Medical laboratories play a central role in health care. Many laboratories are taking a more focused and stringent approach to quality system management. In Korea, laboratory standardization efforts undertaken by the Korean Laboratory Accreditation Program (KLAP) and the Korean External Quality Assessment Scheme (KEQAS) may have facilitated an improvement in laboratory performance, but there are no fundamental studies demonstrating that laboratory standardization is effective. We analyzed the results of the KEQAS to identify significant differences between laboratories with or without KLAP and to determine the impact of laboratory standardization on the accuracy of diagnostic tests. METHODS: We analyzed KEQAS participant data on clinical chemistry tests such as albumin, ALT, AST, and glucose from 2010 to 2013. As a statistical parameter to assess performance bias between laboratories, we compared 4-yr variance index score (VIS) between the two groups with or without KLAP. RESULTS: Compared with the group without KLAP, the group with KLAP exhibited significantly lower geometric means of 4-yr VIS for all clinical chemistry tests (P<0.0001); this difference justified a high level of confidence in standardized services provided by accredited laboratories. Confidence intervals for the mean of each test in the two groups (accredited and non-accredited) did not overlap, suggesting that the means of the groups are significantly different. CONCLUSIONS: These results confirmed that practice standardization is strongly associated with the accuracy of test results. Our study emphasizes the necessity of establishing a system for standardization of diagnostic testing.

Performance Evaluation of Automated Chemistry Analyser for Urine Chemistry Test

BACKGROUND: Prompt and accurate urine chemistry analysis is important to provide information for diagnosis and therapy. In this study, we evaluated the overall performance and utility of an automated chemistry analyser for urine chemistry testing in accordance with Clinical and Laboratory Standards Institute guidelines. METHODS: From January 2015 to March 2015, we evaluated the precision, linearity, limits of detection, carryover, and turnaround times after automation of nine items: total protein, albumin, glucose, blood urea nitrogen, total calcium, magnesium, inorganic phosphate, creatinine, and uric acid. A Hitachi 7600-110 instrument (Hitachi Ltd., Japan) and Hitachi ID Privileged Access Manager (Hitachi Ltd.) were used for automated chemistry analysis and sample preparation, respectively. RESULTS: Regarding precision, the coefficient of variation was 3.9% to 1.6% for high levels and 3.3% to 24.1% for low levels. The linearity and coefficients of determination of all the test items were acceptable. Performance comparison revealed that the two systems were comparable, as evidenced by correlation coefficients >0.975 for most items; moreover, carryover of all items was <1%. The mean turnaround time was 59 minutes. CONCLUSIONS: Urine chemistry testing can be performed with acceptable precision, linearity, and performance by using the Hitachi 7600-110 automated chemistry analyser. The sample preparation system reduces turnaround time, which enhances the clinical utility of urine chemistry testing.

Performance of the Fecal Immunochemical Test for Colorectal Cancer Screening Using Different Stool-Collection Devices: Preliminary Results from a Randomized Controlled Trial

BACKGROUND/AIMS: We are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container). METHODS: In total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia. RESULTS: The FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], −3.4 to 25.6) and 12.0% (95% CI, −0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively. CONCLUSIONS: The impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period.

Performance of the Fecal Immunochemical Test for Colorectal Cancer Screening Using Different Stool-Collection Devices: Preliminary Results from a Randomized Controlled Trial

BACKGROUND/AIMS: We are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container). METHODS: In total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia. RESULTS: The FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], −3.4 to 25.6) and 12.0% (95% CI, −0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively. CONCLUSIONS: The impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period.

Inadvertent Transmission of a Donor's Constitutional Chromosome Abnormality after Hematopoietic Stem Cell Transplantation

A pre-transplant screening work-up of donors for allogeneic hematopoietic stem cell transplantation (HSCT) is essential. Inadvertent transmission of malignancy from donors with subclinical diseases to recipients has been reported recently in several cases. A 49-year-old male was diagnosed with acute myeloid leukemia. He underwent a course of induction chemotherapy and achieved cytogenetic complete remission (CR). He was treated with an additional cycle of consolidation chemotherapy followed by full matched sibling allogeneic HSCT due to an additional deletion in 9q known as an adverse prognostic factor. Post transplantation bone marrow biopsy revealed molecular CR, but conventional cytogenetics identified the presence of 46,XY,t(1:2)(p32:q35). A cytogenetic analysis of the donor graft specimen revealed t(1:2). We confirmed the donor origin of t(1:2). We report the first case of a person with constitutional t(1;2) serving as a stem cell donor.

Improving the Reliability of Clinical Practice Guideline Appraisals: Effects of the Korean AGREE II Scoring Guide

The Korean translated Appraisal of Guidelines for Research and Evaluation II (Korean AGREE II) instrument was distributed into Korean medical societies in 2011. However, inter-rater disagreement issues still exist. The Korean AGREE II scoring guide was therefore developed to reduce inter-rater differences. This study examines the effects of the Korean AGREE II scoring guide to reduce inter-rater differences. Appraisers were randomly assigned to two groups (Scoring Guide group and Non-Scoring Guide group). The Korean AGREE II instrument was provided to both groups. However, the scoring guide was offered to Scoring Guide group only. Total 14 appraisers were participated and each guideline was assessed by 8 appraisers. To evaluate the reliability of the Korean AGREE II scoring guide, correlation of scores among appraisers and domain-specific intra-class correlation (ICC) were compared. Most scores of two groups were comparable. Scoring Guide group showed higher reliability at all guidelines. They showed higher correlation among appraisers and higher ICC values at almost all domains. The scoring guide reduces the inter-rater disagreement and improves the overall reliability of the Korean-AGREE II instrument.

Smartphone-based Mobile Web to Provide Laboratory Test Reference Information / 임상검사와정도관리

BACKGROUND: Majority of clinical laboratories disseminate laboratory test information through guidebooks or handouts. However, these methods cannot instantly confer information, for example, when a novel laboratory test is introduced, or a change is made to a test request procedure or type of specimen involved. To overcome these limitations, we developed a mobile web application that is a laboratory test information repository, initially for use in Korea. METHODS: We established a laboratory master database of searchable laboratory test information using a web-based framework. Information pertaining to clinical test indications, interpretation of test results, and related laboratory tests was revised; test request guidelines were also updated. Information concerning tests that are occasionally subject to change and newly introduced tests was updated promptly. RESULTS: Our mobile web-based application uses the domain name www.schlab.org and can also be accessed via a desktop browser. The information for each test includes basic details such as specimen type, container, turnaround time, and so on and an introduction in addition to a more detailed explanation of associated tests and usage recommendations. The number of monthly visitors to the site was 529 (649 page views), with visitors using the mobile web for 31 seconds per visit. CONCLUSIONS: We developed a mobile web application that provides information on laboratory tests. We improved on the existing method of transmitting such information (i.e., a laboratory request guidebook) by offering a system that provides updated test information and increased accessibility. Our method is expected to reduce instances of inaccurate or unnecessary test orders, improper specimen collection, delayed specimen arrival, and inappropriate treatment.