Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study

BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (\u3e91%)

Evaluation of the fuzzy ARTMAP neural network using off-line and on-line learning strategies

This paper describes an experimental study of the Fuzzy ARTMAP (FAM) neural network as an autonomous learning system for pattern classification tasks. A benchmark database of radar signals from ionosphere has been employed for the system to classify arbitrary sequences of pattern into distinct categories. A number of simulations have been conducted systematically to evaluate the applicability and usefulness of FAM in this context. First, we identify the \u27optimum\u27 parameter settings of FAM for the problem at hand, and investigate the effects of different training schemes and learning rules on classification results, using an off-line learning methodology. We then examine a voting strategy to improve classification accuracy by combining results from multiple FAM classifiers. In addition to off-line learning, we evaluate the prospect of using FAM as an autonomously learning pattern classification system for on-line, non-stationary environments. The performance of FAM is comparable with other reported results, but with the added advantage of on-line and incremental learning

Application of an Adaptive Neural Network to Medical Decision Support

Medical diagnostic and prognostic problems are prime examples of decision making in the face of uncertainty. In this paper, we investigate the applicability of the Fuzzy ARTMAP neural network as an intelligent decision support system in clinical medicine. In particular, Fuzzy ARTMAP is employed as a predictive model for prognosis of complications in patients admitted to the Coronary Care Units. A number of off-line and on-line experiments have been conducted with various network parameter settings, training methods, and learning rules. The results are compared with those from other systems including the logistic regression model. In addition, the outcomes of a set of on-line learning experiments revealed the potential of employing Fuzzy ARTMAP as an autono-mously learning system that is able to learn perpetually and, at the same time, to provide useful decision support. </i

Performance and 12-month Outcomes of a Wire-free Fractional Flow Reserve System for Assessment of Coronary Artery Disease

Background: Fractional flow reserve (FFR) using an invasive pressure wire is recommended to guide coronary revascularisation in stable coronary artery disease. Coronary angiography-based wire-free FFR (CAFFR) determines the significance of a coronary lesion without the requirement of a pressure wire. Deferral of revascularisation of coronary lesions with an FFR >0.8 has been shown to have similar outcomes to patients managed with optimal medical therapy. Objective: The aim of our study was to assess the performance and 12-month clinical outcomes in patients with CAFFR-guided percutaneous coronary intervention (PCI) deferral. Methods: This was a prospective study involving 69 patients (93 vessels) with angiographic stenosis of 30–90%. Patients with CAFFR ≤0.80 or poor image quality were excluded, leaving 29 patients (31 vessels) for analysis. All recruited patients had a CAFFR >0.80 and thus, PCI deferral. This cohort was followed up for 12 months. The primary endpoint was a composite of death from any cause, MI or target vessel revascularisation. Wired FFR was done for comparison on 14 patients (48%) at the operator’s discretion. Results: The mean age was 59.9 (±12.6) years. The majority of patients were men (83%; n=24), 41% (n=12) had diabetes, 62% (n=18) had hypertension, 59% (n=17) had dyslipidaemia, 62% (n=18) had a history of smoking. The mean left ventricular ejection fraction (LVEF) was 52 (±11.4)% and 76% of the patients had a recent acute coronary syndrome. We assessed the left anterior descending artery and 52% (n=16) of vessels had a mean CAFFR was 0.87. At 12 months, all patients were alive, 89.7% remained in chronic coronary syndrome (CCS) class 1 and 3.4% (n=1) of the study population met the primary outcome of target vessel revascularisation. Conclusion: CAFFR showed good agreement with wire-based FFR and 12-month outcomes showed that CAFFR-guided deferral of PCI was safe and comparable to wired-based FFR guidance