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Summary: Background: The introduction of oral direct‐acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re‐treatment is important for budget impact and disease burden projections. Aim: To quantify the number of HCV patients who fail to achieve SVR on oral DAAs (NS5A vs. non‐NS5A) and require re‐treatment. Methods: We used a mathematical model to simulate clinical management of HCV in the USA, which included the implementation of HCV screening, treatment, and disease progression. We simulated different waves of DAA treatment and used real‐world data to extract SVR rates and market shares of available therapies. Results: Our model projected that the number of people living without viraemia (i.e. cured) would increase from 0.70 million in 2014 to 1.78 million by 2020. Between 2014 and 2020, 1.50 million people would receive treatment with DAAs, of whom 124 000 (8.3%) are projected to fail to achieve SVR. Among those treatment failures, 66 600 (53.7%) patients would fail treatment with NS5A inhibitors and 69 600 (56.1%) would have cirrhosis. During the same period, 34 200 people would progress to decompensated cirrhosis and 27 300 would develop hepatocellular carcinoma after failing to achieve SVR. Conclusions: Even in the era of highly effective DAAs, a significant number of patients will fail to achieve SVR and will require re‐treatment options. Timely and effective re‐treatment is essential to prevent the long‐term sequelae of HCV. [ABSTRACT FROM AUTHOR]

Summary: Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely “silent pandemic,” its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high‐level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week. [ABSTRACT FROM AUTHOR]

Background The availability of direct-acting antivirals ( DAAs) has dramatically changed the landscape of hepatitis C virus ( HCV) therapy; however, the cost and budget requirements for DAA treatment have been widely debated. Aims To systematically review published studies evaluating the cost-effectiveness of DAAs for HCV genotype 2-6 infections, and synthesise and re-evaluate results with updated drug prices. Methods We conducted a systematic search of various electronic databases, including Medline, EMBASE, Cochrane library and EconLit for cost-effectiveness studies published from 2011 to 2016. Studies evaluating DAAs for genotypes 2-6 were included. Reported costs, quality-adjusted life-years ( QALYs) and incremental cost-effectiveness ratios ( ICERs) were abstracted. We re-estimated ICERs by varying the price of DAAs from $20 000 to $100 000, and estimated the threshold price at which DAA regimens would be deemed cost-effective ( ICER≤$100 000/ QALY). Results A total of 92 ICERs for 7 different DAA regimens from 10 published articles were included. Among the abstracted 92 ICERs, 20 were for genotype 2, 40 for genotype 3, 30 for genotype 4, 2 for genotype 5 and none for genotype 6; therefore, only genotypes 2-5 were analysed. At the discounted price of $40 000, 87.0% analyses found DAA regiments to be cost-effective, and 7.6% found to be cost-saving. The median threshold price below which DAAs would be deemed cost-effective was between $144 400 and $225 000, and cost-saving between $17 300 and $25 400. Conclusions HCV treatment with DAAs is highly cost-effective in patients with HCV genotypes 2-5 at a $100 000/ QALY threshold. Timely HCV treatment would be an optimal strategy from both a public health and economic perspective. [ABSTRACT FROM AUTHOR]

Background: Discriminating malignant breast lesions from benign ones and accurately predicting the risk of breast cancer for individual patients are crucial to successful clinical decisions. In the past, several artificial neural network (ANN) models have been developed for breast cancer-risk prediction. All studies have reported discrimination performance, but not one has assessed calibration, which is an equivalently important measure for accurate risk prediction. In this study, the authors have evaluated whether an artificial neural network (ANN) trained on a large prospectively collected dataset of consecutive mammography findings can discriminate between benign and malignant disease and accurately predict the probability of breast cancer for individual patients.Methods: Our dataset consisted of 62,219 consecutively collected mammography findings matched with the Wisconsin State Cancer Reporting System. The authors built a 3-layer feedforward ANN with 1000 hidden-layer nodes. The authors trained and tested their ANN by using 10-fold cross-validation to predict the risk of breast cancer. The authors used area the under the receiver-operating characteristic curve (AUC), sensitivity, and specificity to evaluate discriminative performance of the radiologists and their ANN. The authors assessed the accuracy of risk prediction (ie, calibration) of their ANN by using the Hosmer-Lemeshow (H-L) goodness-of-fit test.Results: Their ANN demonstrated superior discrimination (AUC, 0.965) compared with the radiologists (AUC, 0.939; P<.001). The authors' ANN was also well calibrated as shown by an H-L goodness of fit P-value of .13.Conclusions: The authors' ANN can effectively discriminate malignant abnormalities from benign ones and accurately predict the risk of breast cancer for individual abnormalities. [ABSTRACT FROM AUTHOR]

Provides information on a study which assessed psychomotor performance of children on antiepileptic therapy by paper and pencil tests. Research method used; Scores achieved by the groups of children participating in the study; Key findings.

Background and Aims: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population., Methods: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured., Results: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action., Conclusions: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background Atrial fibrillation (AF) screening is endorsed by certain guidelines for individuals aged ≥65 years. Yet many AF screening strategies exist, including the use of wrist-worn wearable devices, and their comparative effectiveness is not well-understood. Methods and Results We developed a decision-analytic model simulating 50 million individuals with an age, sex, and comorbidity profile matching the United States population aged ≥65 years (ie, with a guideline-based AF screening indication). We modeled no screening, in addition to 45 distinct AF screening strategies (comprising different modalities and screening intervals), each initiated at a clinical encounter. The primary effectiveness measure was quality-adjusted life-years, with incident stroke and major bleeding as secondary measures. We defined continuous or nearly continuous modalities as those capable of monitoring beyond a single time-point (eg, patch monitor), and discrete modalities as those capable of only instantaneous AF detection (eg, 12-lead ECG). In total, 10 AF screening strategies were effective compared with no screening (300-1500 quality-adjusted life-years gained/100 000 individuals screened). Nine (90%) effective strategies involved use of a continuous or nearly continuous modality such as patch monitor or wrist-worn wearable device, whereas 1 (10%) relied on discrete modalities alone. Effective strategies reduced stroke incidence (number needed to screen to prevent a stroke: 3087-4445) but increased major bleeding (number needed to screen to cause a major bleed: 1815-4049) and intracranial hemorrhage (number needed to screen to cause intracranial hemorrhage: 7693-16 950). The test specificity was a highly influential model parameter on screening effectiveness. Conclusions When modeled from a clinician-directed perspective, the comparative effectiveness of population-based AF screening varies substantially upon the specific strategy used. Future screening interventions and guidelines should consider the relative effectiveness of specific AF screening strategies.

Background Optimal management of asymptomatic Brugada syndrome (BrS) with spontaneous type I electrocardiographic pattern is uncertain. Methods and Results We developed an individual-level simulation comprising 2 000 000 average-risk individuals with asymptomatic BrS and spontaneous type I electrocardiographic pattern. We compared (1) observation, (2) electrophysiologic study (EPS)-guided implantable cardioverter-defibrillator (ICD), and (3) upfront ICD, each using either subcutaneous or transvenous ICD, resulting in 6 strategies tested. The primary outcome was quality-adjusted life years (QALYs), with cardiac deaths (arrest or procedural-related) as a secondary outcome. We varied BrS diagnosis age and underlying arrest rate. We assessed cost-effectiveness at $100 000/QALY. Compared with observation, EPS-guided subcutaneous ICD resulted in 0.35 QALY gain/individual and 4130 cardiac deaths avoided/100 000 individuals, and EPS-guided transvenous ICD resulted in 0.26 QALY gain and 3390 cardiac deaths avoided. Compared with observation, upfront ICD reduced cardiac deaths by a greater margin (subcutaneous ICD, 8950; transvenous ICD, 6050), but only subcutaneous ICD improved QALYs (subcutaneous ICD, 0.25 QALY gain; transvenous ICD, 0.01 QALY loss), and complications were higher. ICD-based strategies were more effective at younger ages and higher arrest rates (eg, using subcutaneous devices, upfront ICD was the most effective strategy at ages 20-39.4 years and arrest rates >1.37%/year; EPS-guided ICD was the most effective strategy at ages 39.5-51.3 years and arrest rates 0.47%-1.37%/year, and observation was the most effective strategy at ages >51.3 years and arrest rates <0.47%/year). EPS-guided subcutaneous ICD was cost-effective ($80 508/QALY). Conclusions Device-based approaches (with or without EPS risk stratification) can be more effective than observation among selected patients with asymptomatic BrS. BrS management should be tailored to patient characteristics.

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct-acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries' health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro-elimination approach in specific populations is less complex and less costly than country-wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The hepatitis C virus (HCV) care cascade has changed dramatically following the introduction of direct-acting anti-virals (DAAs). Up-to-date estimates of the cascade are needed to monitor progress, identify key gaps and inform policy., Aim: To estimate the current and future HCV care cascade in the United States, nationally and in select subpopulations of interest., Methods: We used a previously validated mathematical model to simulate the landscape of HCV in the United States from 2011 onwards, accounting for HCV screening policy updates, newer HCV treatments and rising HCV incidence., Results: By the end of 2018, of 4.29 million HCV persons alive, 2.71 million (63%) were actively viremic, 2.24 million (52%) aware and 1.58 million (37%) cured. By 2030, under the status quo, of 3.65 million HCV persons alive, 1.88 million (51%) would be viremic, 2.25 million (62%) aware and 1.77 million (49%) cured. The HCV care cascade in 2018 differed substantially by subpopulation: of 1.34 million incarcerated HCV persons, 96% were viremic, 36% aware and 4% cured; of 0.87 million HCV persons in Medicare, 31% were viremic, 72% aware and 69% cured; and of 0.37 million HCV persons in Medicaid, 49% were viremic, 54% aware and 51% cured. Implementing universal screening, providing unrestricted treatment and controlling HCV incidence were factors found to have the largest effect on improving the HCV care cascade., Conclusions: Since the launch of DAAs, the HCV care cascade has shifted towards higher awareness and treatment rates; however, additional interventions are needed to move towards HCV elimination., (© 2019 John Wiley & Sons Ltd.)

Background: Identifying changes in the epidemiology of liver disease is critical for establishing healthcare priorities and allocating resources to develop therapies. The projected contribution of different etiologies toward development of cirrhosis in the United States was estimated based on current publications on epidemiological data and advances in therapy. Given the heterogeneity of published reports and the different perceptions that are not always reconcilable, a critical overview rather than a formal meta-analysis of the existing data and projections for the next decade was performed., Methods: Data from the World Health Organization Global Status Report on Alcohol and Health of 2014, Scientific Registry of Transplant Recipients from 1999 to 2012, National Institute on Alcohol Abuse and Alcoholism, and the Centers for Disease Control and Prevention were inquired to determine future changes in the epidemiology of liver disease., Results: Alcohol consumption has increased over the past 60 years. In 2010, transplant-related costs for liver recipients were the highest for hepatitis C (~$124 million) followed by alcohol-related cirrhosis (~$86 million). We anticipate a significant reduction in incidence cirrhosis due to causes other than alcohol because of the availability of high efficiency antiviral agents for hepatitis C, universal and effective vaccination for hepatitis B, relative stabilization of the obesity trends in the United States, and novel, potentially effective therapies for nonalcoholic steatohepatitis. The proportion of alcohol-related liver disease is therefore likely to increase in both the population as a whole and the liver transplant wait list., Conclusions: Alcohol-related cirrhosis and alcohol-related liver disorders will be the major cause of liver disease in the coming decades. There is an urgent need to allocate resources aimed toward understanding the pathogenesis of the disease and its complications so that effective therapies can be developed., (Copyright © 2015 by the Research Society on Alcoholism.)