Comparative performance of various human papillomavirus assays available in Korea for detecting cervical intraepithelial neoplasia.

AIM: The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS: Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS: A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p < 0.05) compared to Cobas 4800, in aspect of high-risk HPV positive, Anyplex II HPV28 showed increased sensitivity (96.9%, p < 0.05). CONCLUSION: The performance of the HPV genotype test that were commonly used in Korea was concordant with Cobas HPV test. Further studies are needed to evaluate the safety, efficiency, and cost-effectiveness of the various commercially available domestic HPV assays.

Discrepancy between Cytology and Histology in Cervical Cancer Screening: a Multicenter Retrospective Study (KGOG 1040).

BACKGROUND: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells. Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. METHODS: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. RESULTS: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7 (19-88) years and mean BMI was 22.5 (16.9-34.1) kg/m². The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475-3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367-0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385-2.469). CONCLUSION: Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Outcomes After Use of Standard- and Low-Dose Non-Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

Background and Purpose- Limited data are available describing the relative effectiveness, safety, and optimal dosing of non-vitamin K antagonist oral anticoagulants (NOACs) for treatment of nonvalvular atrial fibrillation in East Asian patients. We tried to compare effectiveness and safety outcomes of standard- and low-dose NOACs and warfarin in this population. Methods- Using nationwide administrative claims-based datasets from the Korean National Health Insurance Service Database (July 1, 2015, to December 31, 2016), this study comprised 56 504 anticoagulation-naive nonvalvular atrial fibrillation patients with high thromboembolic risk (CHA2DS2-VASc score, ≥2) treated with oral anticoagulants. Main study outcomes included thromboembolic events (ischemic stroke or systemic embolism), major bleeding, and mortality. Results- Among the study patients, 10 409 (18.4%) received warfarin and 46 095 (81.6%) were treated with NOACs: dabigatran (n=12 593; 22.3%), rivaroxaban (n=21 000; 37.2%), and apixaban (n=12 502; 22.1%). Low-dose NOAC (75.1% dabigatran, 59.7% rivaroxaban, and 62.7% apixaban) was more frequently used than standard-dose NOAC. During median follow-up of 15.0 months, each NOAC was associated with significantly lower risk of thromboembolic events (hazard ratio [HR], 0.76; 95% CI, 0.75-0.81 for dabigatran; HR, 0.74; 95% CI, 0.65-0.83 for rivaroxaban; and HR, 0.68; 95% CI, 0.59-0.78 for apixaban). Regarding safety outcomes, dabigatran (HR, 0.81; CI, 0.69-0.95) and apixaban (HR, 0.67; CI, 0.56-0.79) were associated with lower risk of major bleeding but not with rivaroxaban (HR, 0.96; CI, 0.84-1.11). Among adults <75 years of age without chronic kidney disease, use of low-dose apixaban did not demonstrate clinical benefit over warfarin with respect to thromboembolic events (HR, 0.99; CI, 0.76-1.28) and mortality (HR, 0.85; CI, 0.62-1.16). Conclusions- In this cohort of East Asian patients with nonvalvular atrial fibrillation, NOACs were associated with better effectiveness and safety outcomes versus warfarin. Lower NOAC doses were more often used, but an unjustified underdosing of apixaban seems to result in lower clinical benefit.

A systematic review on current status of health technology reassessment: insights for South Korea.

BACKGROUND: To systematically investigate the current status and methodology of health technology reassessment (HTR) in various countries to draw insights for the healthcare system in South Korea. METHODS: A systematic literature search was conducted on the articles published between January 2000 and February 2015 on Medline, EMBASE, the Cochrane Library, CINAHL, and PubMed. The titles and abstracts of retrieved records were screened and selected by two independent reviewers. Data related to HTR were extracted using a pre-standardised form. The review was conducted using narrative synthesis to understand and summarise the HTR process and policies. RESULTS: Forty five studies, conducted in seven countries, including the United Kingdom, Australia, Canada, Spain, Sweden, Denmark, and the United States of America, fulfilled the inclusion criteria. Informed by the literature review, and complemented by informant interviews, we focused on HTR activities in four jurisdictions: the United Kingdom, Canada, Australia, and Spain. There were similarities in the HTR processes, namely the use of existing health technology assessment agencies, reassessment candidate technology identification and priority setting, stakeholder involvement, support for reimbursement coverage, and implementation strategies. Considering the findings of the systematic review in the context of the domestic healthcare environment in Korea, an appropriate HTR model was developed. This model included four stages, those of identification, prioritisation, reassessment and decision. CONCLUSIONS: Disinvestment and reinvestment through the HTR was used to increase the efficiency and quality of care to help patients receive optimal treatment. Based on the lessons learnt from other countries' experiences, Korea should make efforts to establish an HTR process that optimises the National Healthcare Insurance system through revision of the existing Medical Service Act.

EARLY ASSESSMENT AND PREDICTION OF POTENTIAL IMPACT OF THE IMPLANTATION OF POLYURETHANE SCAFFOLD IN PARTIAL MENISCAL LESIONS: A PILOT HORIZON SCANNING ACTIVITY IN SOUTH KOREA.

OBJECTIVES: The aim of this study was to predict the potential impact of the introduction of implantation of polyurethane scaffold for the treatment of partial meniscal lesions in the South Korean healthcare system. METHODS: The horizon scanning process was used to select a target technology and assess its potential impacts on patients and the Korean healthcare system. We identified and filtered research-phase health technologies that are not listed yet in Korean, but appear promising. After a process of prioritization, we chose the implantation of polyurethane scaffolds as a target technology. Then, through the procedures of assessment and peer review, we analyzed current evidence and its predicted potential impacts. RESULTS: There were eight studies included in the review: one prospective cohort and seven case-series studies. Six revealed significant improvements in function and pain relief. Of the six studies, which reported safety endpoints, four stated no major postoperative complications related to scaffold, and two reported adverse events and serious adverse events such as pain, joint swelling, et cetera. We also included the potential impact of this technology based on the experts' consultation. They all agreed that it would satisfy the diverse needs of patients and fulfill clinical needs. However, the majority of related clinical studies were based on short-term follow-up observations without any validation process involving comparison with control groups. CONCLUSIONS: Through a horizon scanning activity, we found that the implantation of polyurethane scaffolds is a promising technology to resolve articular cartilage defects; however, long-term evidence with comparison groups for safety and effectiveness is required.

Pattern and Impact of Off-label Underdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Who are Indicated for Standard Dosing.

With safety concerns about increasing bleeding, off-label underdosing of non-vitamin K antagonist anticoagulants (NOACs) is common in East Asian patients with atrial fibrillation (AF). We tried to investigate the pattern of NOAC underdosing and associated clinical outcomes in patients with AF who are indicated for standard dosing. Using the Korean National Health Insurance Service database, we evaluated 16,568 patients with a new prescription of NOAC who are indicated for standard NOAC dosing and compared 4,536 patients with warfarin with respect to thromboembolic events (ischemic stroke or systemic embolization), all-cause mortality and major bleeding. Of the 16,568 patients indicated for standard NOAC dosing, 8,549 (51.9%) received off-label underdosing (50.6% rivaroxaban, 53.0% apixaban). During a median follow up of 15.0 months, as compared with warfarin, underdosing of rivaroxaban was associated with lower risks of major thromboembolic events (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.41 to 0.69) and all-cause mortality (HR 0.57, 95% CI: 0.41 to 0.82), and a similar risk of major bleeding (HR 1.10, 95% CI: 0.82 to 1.46). However, underdosing of apixaban was associated with similar risks of major thromboembolic events (HR: 0.90; 95% CI: 0.70 to 1.16), all-cause mortality (HR 0.94, 95 CI: 0.71 to 1.24) and major bleeding (HR 0.84, 95% CI: 0.61 to 1.17). In conclusion, in this Korean population with AF who are indicated for standard NOAC dosing, off-label underdosing is common and its clinical benefit over warfarin was inconsistent according to types of NOAC. Notably, apixaban underdosing provides no benefit in effectiveness compared with warfarin.

Safety and Effectiveness of Contemporary P2Y12 Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study.

Background Prior reports indicate that the effect of P2Y12 inhibitors may be different in East Asian patients ("East Asian paradox"); therefore, understanding the outcomes associated with potent P2Y12 inhibitors in different populations is clinically important. Methods and Results In this observational cohort study using administrative healthcare data sets, we compared safety and effectiveness of contemporary P2Y12 inhibitors in patients with acute coronary syndrome. The primary safety outcomes were major and any bleeding, and the primary effectiveness outcomes were major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) and all-cause mortality. Among 70 715 patients with acute coronary syndrome, 56 216 (79.5%) used clopidogrel, 11 402 (16.1%) used ticagrelor, and 3097 (4.4%) used prasugrel. The median follow-up period was 18.0 months (interquartile range: 9.6-26.4 months). In a propensity-matched cohort, compared with clopidogrel, ticagrelor was associated with a higher risk of any bleeding (hazard ratio: 1.23; 95% CI, 1.14-1.33) but a lower risk of mortality (hazard ratio: 0.76; 95% CI, 0.63-0.91). Prasugrel, compared with clopidogrel, was associated with higher risks of any bleeding (hazard ratio: 1.23; 95% CI, 1.06-1.43) and major bleeding (hazard ratio: 1.50; 95% CI, 1.01-2.21) but a similar risk of effectiveness outcomes. No significant difference was noted between ticagrelor and prasugrel with respect to key safety or effectiveness outcomes. Several sensitivity analyses showed similar results. Conclusions In East Asian patients with acute coronary syndrome, compared with clopidogrel, ticagrelor was associated with an increased risk of bleeding but a decreased risk of mortality. Prasugrel was associated with an increase of any bleeding without difference in effectiveness outcomes. The risks of bleeding and ischemic events were similar between ticagrelor and prasugrel.