Clinical and economic burden of immune tolerance induction in entire patients with hemophilia A: Insights from a real-world Korean setting.

INTRODUCTION: The most notable challenge facing hemophilia A treatment is the development of inhibitors against factor VIII, resulting in increased clinical and socioeconomic burdens due to the need for expensive bypassing agents (BPAs). Although immune tolerance induction (ITI) is currently the primary approach for inhibiting and reducing the inhibitors, the lengthy duration of ITI necessitates the continued use of BPA to manage bleeding episodes. In this study, we aimed to obtain real-world evidence on the clinical and economic aspects and associated burdens experienced by patients with hemophilia A with inhibitors undergoing ITI in Korea. METHODS: Claims data from January 1, 2007, to December 31, 2020, were used in this study. The study cohort comprised patients with hemophilia A undergoing ITI, who were categorized into three groups: successful, failed, or continuation of ITI. We evaluated clinical and economic burdens, including monthly healthcare visits, medication costs, and total medical expenses. RESULTS: The study involved 33 cases of ITI across 32 patients. Excluding seven continuation cases where success could not be determined at the observation point, the estimated success rate of ITI was 80.8 %. The median duration of ITI for all patients was 25.7 months. While no significant disparities were noted in the ITI duration between successful and unsuccessful cases (24.51 vs. 25.66 months), substantial discrepancies were observed in the duration of BPA usage (11.10 vs. 25.66 months) and the number of prescribed BPAs (1.79 vs. 2.97). CONCLUSION: Successful ITI reduced both clinical and economic burdens, resulting in decreased monthly medication expenses and overall medical costs.

Deep learning-based imaging reconstruction for MRI after neoadjuvant chemoradiotherapy for rectal cancer: effects on image quality and assessment of treatment response.

PURPOSE: To investigate the effects of deep learning-based imaging reconstruction (DLR) on the image quality of MRI of rectal cancer after chemoradiotherapy (CRT), and its accuracy in diagnosing pathological complete responses (pCR). METHODS: We included 39 patients (men: women, 21:18; mean age ± standard deviation, 59.1 ± 9.7 years) with mid-to-lower rectal cancer who underwent a long-course of CRT and high-resolution rectal MRIs between January 2020 and April 2021. Axial T2WI was reconstructed using the conventional method (MRIconv) and DLR with two different noise reduction factors (MRIDLR30 and MRIDLR50). The signal-to-noise ratio (SNR) of the tumor was measured. Two experienced radiologists independently made a blind assessment of the complete response on MRI. The sensitivity and specificity for pCR were analyzed using a multivariable logistic regression analysis with generalized estimating equations. RESULTS: Thirty-four patients did not have a pCR whereas five (12.8%) had pCR. Compared with the SNR of MRIconv (mean ± SD, 7.94 ± 1.92), MRIDLR30 and MRIDLR50 showed higher SNR (9.44 ± 2.31 and 11.83 ± 3.07, respectively) (p < 0.001). Compared to MRIconv, MRIDLR30 and MRIDLR50 showed significantly higher specificity values (p < 0.036) while the sensitivity values were not significantly different (p > 0.301). The sensitivity and specificity for pCR were 48.9% and 80.8% for MRIconv; 48.9% and 88.2% for MRIDLR30; and 38.8% and 86.7% for MRIDLR50, respectively. CONCLUSION: DLR produced MR images with higher resolution and SNR. The specificity of MRI for identification of pCR was significantly higher with DLR than with conventional MRI.

Health disparity and healthcare utilization inequity among older adults living in poverty in South Korea: a cross-sectional study.

BACKGROUND: Korea has a two-tiered universal health security system: the wage-based National Health Insurance (NHI) program and government-subsidized Medical Aid (MA) program. Beneficiaries of the MA program belong to the lowest economic class. This study aims to investigate the association between economic status-defined as NHI or MA enrollment-and health disparity of older people aged ≥ 65 years in South Korea. METHODS: The claims records of 672,525 older age population from the 2017 Health Insurance Review and Assessment Service-Adult Patient Sample were used to estimate adjusted odds ratios (aORs) of MA vs. NHI beneficiaries for prevalence for common geriatric diseases. Logistic regression and negative binomial regression were used to investigate the association between economic status and prevalence or healthcare utilization for each disease. RESULTS: MA beneficiaries showed significantly higher prevalence than NHI beneficiaries for seven out of nine diseases (aORs ranging from 1.18 to 1.95). The discrepancy in the prevalence between the two groups was highest among those aged 65-69 years (aORs: 1.34-2.94), and diminished as they got older (aORs: 1.05-1.67). MA beneficiaries had significantly more outpatient visits to treat six diseases (aORs: 1.07-1.28), and more hospitalization to treat seven diseases (aORs:1.08-1.73) than NHI beneficiaries. CONCLUSION: The higher prevalence of common geriatric diseases among MA than NHI beneficiaries confirms unfavorable health disparity in the elderly living in extreme poverty. Similar or higher healthcare utilization in treating the same conditions among MA beneficiaries suggests a low possibility of inequity for access to healthcare resources covered by the universal health security system due to poor economic status. Greater excess use of inpatient than outpatient care by MA beneficiaries implies that the condition of poor older adults might be more severe when diagnosed with the same disease.

Assessment of Device Neoendothelialization With Cardiac Computed Tomography Angiography After Transcatheter Closure of Atrial Septal Defect.

BACKGROUND: Although the transcatheter closure of atrial septal defect was established as the treatment of choice several decades ago, the process of device neoendothelialization (NE) in humans is not well understood. We aimed to measure the extent of device NE using cardiac computed tomography angiography and analyze its risk factors. METHODS: Between January 2005 and February 2021, we retrospectively reviewed 164 devices of 112 patients on cardiac computed tomography angiography. We investigated device shape, contrast opacification within the device that differentiated device NE, and device-related thrombosis or vegetation. Risk factor analysis for major adverse cardiovascular events and incomplete NE according to the postprocedural period was performed. RESULTS: Seventy patients (62.5%) were women, with a median (range) age at the time of device closure of 44.5 (0.6-79.2) years. The mean (±SD) defect size was 16.6 (±7.8) mm, and patients were followed for 35.9±33.9 months. After 6 months of device implantation, 35% of the devices (42/120) had incomplete NE. The intensity of intradevice opacification shifted from complete to partial or nonopacification over time (P<0.001), and a similar pattern was observed in the shunt flow (P<0.001). The bulkiness of devices also decreased in proportion to the postprocedural period (P<0.001). Risk analysis revealed device diameter (hazard ratio, 1.18 [95% CI, 1.04-1.27]; P<0.001) as the only significant factor of incomplete NE and major adverse events. CONCLUSIONS: Incomplete NE of atrial septal defect devices was identified on cardiac computed tomography angiography in significant numbers after 6 months of the procedure. The device diameter was related to incomplete NE and major adverse events. Further prospective and multicenter studies are warranted to validate this new assessment of device NE.

Appendicular skeletal muscle mass assessment in dogs: a scoping literature review.

BACKGROUND: Monitoring changes in appendicular skeletal muscle mass is frequently used as a surrogate marker for limb function. The primary objective of this study was to review scientific information related to the assessment of appendicular skeletal muscle mass in dogs. The secondary objective was to develop practical recommendations for serial evaluation of muscle mass. METHODS: A scoping review was conducted with a systematic search of PubMed, Web of Science, CAB abstract, and Cochrane from inception to June 2021. The following modalities were included in the search: limb circumference, diagnostic ultrasound, computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry. RESULTS: A total of 62 articles that measured appendicular skeletal muscle mass in dogs were identified. Limb circumference (55 articles) was the most commonly used modality. Its reliability was investigated in five studies. Several factors, including measuring tape type, body position, joint angles, and the presence of hair coat, were reported as variables that can affect measurements. Diagnostic ultrasound (five articles) was validated in three articles, but there is scarce information about observer reliability and variables affecting the measurement. Computed tomography (four articles) and magnetic resonance imaging (one article) have been used to validate other modalities at a single time point rather than as a clinical tool for serial muscle mass monitoring. Dual-energy x-ray absorptiometry (two articles) has been used to quantify specific skeletal muscle mass but was mainly used to evaluate body composition in dogs. CONCLUSION: Limb circumference and ultrasound are likely the main modalities that will continue to be used for serial muscle mass measurement in the clinical setting unless a new technology is developed. The reliability of limb circumference is questionable. Several key factors, including measuring tape type, body position, joint angles, and coat clipping, need to be controlled to improve the reliability of limb circumference measurements. Ultrasound may provide a reasonable alternative, but further studies are required to evaluate the reliability of this modality and identify factors that influence ultrasound measurements.

Epidemiological Features and Economic Burden of Guillain-Barré Syndrome in South Korea: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: Guillain-Barré syndrome (GBS) is rare, but its symptoms are severe and they occasionally lead to long-term disability. Country-specific epidemiological evidence is useful for detecting potential problems at the population level. This study investigated the epidemiological and economic characteristics of GBS in South Korea. METHODS: The Korean National Health Insurance Service claims data from 2010 to 2016 were used to identify incident cases as newly hospitalized patients with a primary diagnosis of GBS (the 10th revision of the International Classification Disease code of G61.0). New cases were defined as patients not having claim records for GBS within one year prior to the hospital admission for GBS. RESULTS: The incidence rate increased by 45.6% between 2010 and 2016, from 1.28 to 1.82 per 100,000 population. All age groups other than <20 years showed increasing trends. The incidence rate was highest in those aged 65 years to 74 years. Approximately 72% of the incident GBS cases had antecedent infection within 42 days before GBS was diagnosed. Children younger than 10 years constituted the highest proportion of antecedent infections (93.7%). The average length of stay per GBS hospitalization was 33.5 days. Patients had an average of 7.48 outpatient visits for GBS treatment per year. The economic burden from a societal perspective of treating GBS during the first year was USD 16,428. CONCLUSIONS: The increasing incidence trend and substantial economic burden of GBS strongly advocate the development of effective strategies for preventing and managing GBS.

Cost-utility analysis of emicizumab prophylaxis in haemophilia A patients with factor VIII inhibitors in Korea.

AIMS: Haemophilia A patients with factor VIII inhibitors (HAPI) experience frequent spontaneous bleeding, approximately once a week, and require expensive bypassing agent (BPA) treatments to control bleeding over their lifetime. According to the HAVEN 1 trial, weekly emicizumab (Hemlibra®) prophylaxis injection reduces annualized bleeding rates (ABR) by 87% compared with BPA on-demand treatment (BPA-OD) administered at the time of bleeding. Our study aimed to assess the cost-effectiveness of emicizumab prophylaxis in HAPI in Korea. METHODS: Using a lifetime Markov model with health states of 'alive with bleeds' and 'dead', we simulated the experience of HAPI receiving emicizumab prophylaxis (treatment arm) or BPA-OD (control arm) and estimated expected clinical and economic outcomes under each treatment arm. Model parameters included comparative effectiveness, clinical and epidemiologic characteristics of Korean HAPI, costs of drug treatment and medical events and utility for 'alive with bleeds' state under each treatment. We utilized local data, including National Health Insurance claims data, national statistics, literature and expert surveys with haematologists. RESULTS: Base-case analysis results showed that compared with BPA-OD, lifetime emicizumab prophylaxis prevented 807 bleedings, extended 3.04 quality-adjusted life-years and reduced costs by 2.6 million US dollars. Thus, emicizumab prophylaxis is a dominant treatment option with better effectiveness and lower costs than BPA-OD. A series of one-way sensitivity analyses consistently showed dominant results, confirming that lifetime emicizumab prophylaxis is a cost-saving intervention for HAPI. CONCLUSION: Emicizumab prophylaxis is an excellent treatment choice reducing ABR, improving quality of life and reducing costs.

Cost-utility analysis of pralatrexate for relapsed or refractory peripheral T-cell lymphoma based on a case-matched historical control study along with single arm clinical trial.

BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) treated with pralatrexate have previously shown superior overall survival (OS) compared to those who underwent conventional chemotherapy (CC, 15.4 vs. 4.07 months). We conducted an economic evaluation of pralatrexate from a societal perspective in Korea based on data from the PROPEL phase II study. METHODS: Using a Markov model with a weekly cycle, we simulated the experience of patients with R/R PTCL receiving pralatrexate or CC for 15 years. The model consists of five health states; initial treatment, treatment pause, subsequent treatment, stem cell transplantation (SCT) success, and death. Comparative effectiveness was based on PROPEL phase II single-arm study and its matched historical control analysis. Costs included drug, drug administration, monitoring, adverse event management, and SCT costs. RESULTS: The incremental cost-effectiveness ratio of the base case was $39,153 per quality-adjusted life-year (QALY) gained. The results of one-way sensitivity analysis ranged from $33,949 to $51,846 per QALY gained, which remained within an implicit willingness-to-pay (WTP) threshold of anticancer drugs in Korea. CONCLUSIONS: Pralatrexate is a cost-effective intervention with improved OS and incremental costs within the WTP limit. Pralatrexate could function as a new therapeutic option for patients suffering from life-threatening R/R PTCL.

Causality Assessment Guidelines for Adverse Events Following Immunization with a Focus on Guillain-Barré Syndrome.

South Korea operates a National Vaccine Injury Compensation Program (VICP) for people who experience adverse events following immunization (AEFI). To run this program rationally, it is a prerequisite to confirm whether adverse events were caused by immunization. Guillain-Barré syndrome (GBS), a severe neurological disease with limb pain and muscle weakness as cardinal symptoms, is attracting attention as an AEFI. However, algorithm or guidelines for assessing the causality between vaccination and the incidence of GBS are lacking. We aimed to develop guidelines for causality assessment of GBS as an AEFI and suggest using these guidelines in alignment with the VICP. We systematically searched for other previously published algorithms or guidelines and found a WHO-AEFI guideline used worldwide; however, it only provides general instructions and is not tailored to specific adverse events. We translated and locally adapted the structure of this guideline and then added contents related to GBS. The GBS-specific guideline consists of four steps: case ascertainment of GBS, checklist (including (1) order of incidence, (2) temporal proximity, (3) evidence for other causes and (4) published evidence), an algorithm, and final classification. We listed key information on confirming GBS and whether any other causes of GBS were present. For real world application of the guideline along with the VICP, we collaborated with a panel of neurologists, epidemiologic investigators, and committee members from the VICP. To ensure transparency and a scientific approach, regular updates and collaboration with neurologists are essential. We expect that this guideline will contribute to logical causality assessment and compensation decisions for GBS and will provide the basic structure for causality assessment of other AEFIs.

Socioeconomic Impact of the Rotavirus Vaccine in Korea: Comparing the Epidemiologic and Economic Characteristics of Rotavirus Gastroenteritis Before and After the Introduction of Vaccines.

BACKGROUND: Since the introduction of 2 rotavirus (RV) vaccines in Korea, the vaccination rate has reached over 80% with out-of-pocket spending in the private market. We investigated the socioeconomic impact of RV vaccines in Korea to assess their value and public health contribution. METHODS: By using National Health Insurance Service claims data, we compared the epidemiologic and economic characteristics of rotavirus gastroenteritis (RVGE) before and after the introduction of RV vaccines. For each year of the study period, the annual prevalence and national costs of RVGE were estimated based on children under 5 years with at least 1 National Health Insurance Service claims record with a diagnosis of RVGE. RESULTS: Compared with the prevaccination period, the prevalence of RVGE decreased in the postvaccination period by 48.9% from 2097 per 100,000 children in 2006 to 1072 per 100,000 children in 2015, implying an increase in the vaccination rate and the prevention effect of the vaccines. The highest reduction was observed among those 12 to <24 months of age (-73.4%), presumably due to the benefit of full vaccination, while children under 2 months, ineligible for the RV vaccine, showed an increase (41.7%). The number of hospitalized RVGE cases per year decreased by 69.0%. The national economic burden of RVGE decreased by 28.6%. CONCLUSIONS: The substantial reduction in the socioeconomic burden of RVGE after the introduction of RV vaccines confirms their benefit to society. This study would help health policy makers make empirical decisions on incorporating the vaccination into national immunization programs.

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study.

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.

Assessment of the therapeutic response of hepatocellular carcinoma treated with transcatheter arterial chemoembolization: comparison of contrast-enhanced sonography and 3-phase computed tomography.

OBJECTIVE: The purpose of this study was to compare contrast-enhanced sonography with 3-phase computed tomography (CT) in assessing the therapeutic response of hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE). METHODS: Twenty-nine nodular HCCs treated with TACE were examined with contrast-enhanced sonography, 3-phase helical CT, and conventional angiography. Contrast-enhanced sonographic and CT findings were interpreted separately and prospectively for the presence or absence of contrast enhancement in the treated HCCs. Conventional angiography served as the reference standard. RESULTS: Intratumoral enhancement was seen in 19 HCCs (61%) on contrast-enhanced sonography and 12 HCCs (39%) on CT. Enhancement patterns on sonography were blush in 8 (42%), branching in 2 (11%), nodular in 4 (21%), and stippled in 5 (26%). Of the 19 HCCs with intratumoral enhancement on contrast-enhanced sonography, 13 (68%) showed tumor staining on angiography. Of the 12 HCCs without intratumoral enhancement on sonography, 1 (8%) showed tumor staining on angiography. The sensitivity and specificity of contrast-enhanced sonography in depicting flow in HCCs treated with TACE were 93% and 65%, respectively. The sensitivity and specificity of 3-phase CT were 64% and 100%. CONCLUSIONS: Contrast-enhanced sonography is a more sensitive imaging method than 3-phase CT in depicting vascularity in HCCs treated with TACE.

False-negative results at multi-detector row CT colonography: multivariate analysis of causes for missed lesions.

PURPOSE: To determine causes of false-negative results at multi-detector row computed tomographic (CT) colonography and determine presumptive causes with logistic regression analysis. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. The study included 394 colonic segments in 31 men and 25 women at high risk for colorectal cancer (mean age +/- standard deviation, 60.2 years +/- 9.3 for men and 56.8 years +/- 13.3 for women). Multi-detector row CT colonography and colonoscopy (reference standard) were performed in a blinded manner, and the results were compared. CT colonographic findings were interpreted in consensus by two readers using a primary two-dimensional with three-dimensional problem-solving approach. Adequacy of colonic preparation and distention was recorded. Sensitivity and specificity were obtained with 95% confidence intervals (CIs). Lesions missed at CT colonography were retrospectively reassessed to identify why they were missed, and, if the causes were not apparent, logistic regression analysis was performed to determine the presumptive causes. RESULTS: Colonic preparation and distention were optimal in 17 patients (30%) but suboptimal in 37 (66%) and poor enough to make the results nondiagnostic in two (4%). Twenty-nine of 63 lesions were missed at CT colonography. When all flat, sessile, and pedunculated lesions (n = 63) were included, sensitivities were 75% (nine of 12; 95% CI: 48%, 100%) for lesions 10 mm or larger and 79% (19 of 24; 95% CI: 65%, 93%) for those 6 mm or larger. When only sessile and pedunculated lesions (n = 60) were included, corresponding sensitivities were 100% (nine of nine; 73%, 100%) and 90% (19 of 21; 78%, 100%), respectively. All three missed lesions larger than 10 mm were flat, and all three flat lesions were missed. Two 3-mm high lesions, including one invasive adenocarcinoma, were misinterpreted as feces at blinded image review; one 1-mm high tubular adenoma with adenocarcinoma foci could not be visualized even in retrospect. Sessile or pedunculated polyps 5 mm or smaller were significantly more likely to be missed than those 6 mm or larger (adjusted odds ratio, 11.6; P = .027). CONCLUSION: Aside from inadequate bowel preparation and/or distention, flat lesions and small polyps are the two main causes for missed lesions at multi-detector row CT colonography.