Initial uptake, time to treatment, and real-world effectiveness of all-oral direct-acting antivirals for hepatitis C virus infection in the United States: A retrospective cohort analysis

BACKGROUND: Data on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies. METHODS: A retrospective cohort analysis was undertaken using electronic medical records and chart review abstraction of hepatitis C virus-infected individuals aged >18 years diagnosed with chronic hepatitis C virus infection between January 1, 2014, and December 31, 2015 from the Indiana University Health database. RESULTS: Eight hundred thirty people initiated direct-acting antiviral therapy during the 2-year observation window. The estimated incidence of treatment initiation was 8.8%±0.34% at the end of year 1 and 15.0%±0.5% at the end of year 2. Median time to initiating therapy was 300 days. Using a Cox regression analysis, positive predictors of treatment initiation included age (hazard ratio, 1.008), prior hepatitis C virus treatment (1.74), cirrhosis (2.64), and history of liver transplant (1.5). History of drug abuse (0.43), high baseline alanine aminotransferase levels (0.79), hepatitis B virus infection (0.41), and self-pay (0.39) were negatively associated with treatment initiation. In the evaluable population (n = 423), 83.9% (95% confidence interval, 80.1-87.3%) of people achieved sustained virologic response. CONCLUSION: In the early years of the direct-acting antiviral era, <10% of people diagnosed with chronic hepatitis C virus infection received direct-acting antiviral treatment; median time to treatment initiation was 300 days. Future analyses should evaluate time to treatment initiation among those with less advanced fibrosis

Progression of the FIB-4 index among patients with chronic HCV infection and early liver disease

Background and aims:Historical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease progression according to the non-invasive Fibrosis-4 (FIB-4) index in patients with chronic HCV and early disease. Methods and results:Patients diagnosed with chronic HCV and FIB-4 &lt;3.25 from four international liver clinics were included in a retrospective cohort study. Follow-up ended at start of antiviral therapy resulting in sustained virological response, at time of liver transplantation or death. Primary outcome of advanced liver disease was defined as FIB-4 &gt;3.25 during follow-up. Survival analyses were used to assess time to FIB-4 &gt;3.25. In total, 4286 patients were followed for a median of 5.0 (IQR 1.7-9.4) years, during which 41 071 FIB-4 measurements were collected. At baseline, median age was 47 (IQR 39-55) years, 2529 (59.0%) were male, and 2787 (65.0%) patients had a FIB-4 &lt;1.45. Advanced liver disease developed in 821 patients. Overall, 10-year cumulative incidence of advanced disease was 32.1% (95% CI 29.9% to 34.3%). Patients who developed advanced disease showed an exponential FIB-4 increase. Among patients with a presumed date of HCV infection, cumulative incidence of advanced disease increased 7.7-fold from 20 to 40 years as opposed to the first 20 years after HCV infection. Conclusions:The rate of advanced liver disease is high among chronic HCV-infected patients with early disease at time of diagnosis, among whom liver disease progression accelerated over time. These results emphasise the need to overcome any limitations with respect to diagnosing and treating all patients with chronic HCV across the globe.</p

Effectiveness of Golimumab as Second Anti-TNFα Drug in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis in Italy: GO-BEYOND, a Prospective Real-World Observational Study

In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP &lt; 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy

Real-world effectiveness and persistence of golimumab as second-line anti-TNFα drug in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis patients in Italy: GO-BEYOND, a 12-month prospective observational study

A high proportion of patients may fail a first-line anti-TNF drug, necessitating the switch to another anti-TNF treatment. After 12 months of GLM treatment, 80% of RA patients achieved low disease activity (LDA), 37.1% with PsA achieved minimal disease activity and 55.3% with axSpA achieved LDA while persistence at 12 months in all patients was 77.7%. In this 1-year analysis of the GO-BEYOND study in Italy, GLM had a favorable benefit: risk profile and high retention rate in patients with PsA, RA and axSpA

Adipokines: Linking metabolic syndrome, the immune system, and arthritic diseases

Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases. Chronic low-grade inflammation associated with obesity has been established as a significant contributing factor to the increased prevalence of MetS. Adipokines, which play important physiological roles in metabolic activities contributing to the pathogenesis of MetS, are also involved in the regulation of autoimmune and/or inflammatory processes associated with arthritic diseases. Therefore, MetS and dysregulated secretion of pro-inflammatory adipokines have been recognized as a molecular link between CVD and arthritis diseases. In the present paper, we review recent evidence supporting the role played by adipokines, in particular leptin, adiponectin, and lipocalin-2, in the modulation of the immune system, MetS and arthritic diseases. The underlying cellular and molecular mechanisms are discussed, as well as potential new therapeutic strategies.Acknowledgments: OG and FL are Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). VF is a “Sara Borrell” Researcher funded by ISCIII and FEDER (CD16/00111). RG is a “Miguel Servet” Researcher funded by Instituto de Salud Carlos III (ISCIII) and FEDER. CRF is a pre-doctoral research scholar funded by ISCIII and FEDER (Exp.18/00188). OG, MAGG, and RG are members of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. FL is a member of CIBERCV (Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares). The work of OG and JP (PI17/00409), RG (PI16/01870 and CP15/00007) and FL (PI15/00681 PI18/00821 and CB16/11/00226) were funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). RG is beneficiary of a project funded by Mutua Madrileña 2018. AM wishes to acknowledge financial support from the European Structural and Social Funds through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity ‘Improvement of researchers’ qualification by implementing world-class R&D projects’ of Measure No. 09.3.3-LMT-K-712 (grant application code: 09.3.3-LMT-K-712-01-0157, agreement No. DOTSUT-215) and the new funding programme: Attracting Foreign Researchers for Research Implementation (2018–2022). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript

Three essays on demand for freight transportation optimization, spatial econometrics and parametric estimations

The dissertation evaluates the demand for grain transportation using different methodologies such as a spatial Tobit demand estimation and the optimization models. The first essay, taking account of the spatial interactions, develops the Tobit demand system with different spatial weight matrices, which represents spatial effects on demand for transportation among neighboring elevators. I proposed the new methodology of systematically constructing an unequal weight matrix for the spatial Tobit demand model through the use of Geographic Information System (GIS). The main results indicate a significant negative impact of the spatial factor in the demand for rail transportation and heterogeneity among elevator companies.; The second essay examines the effects of Identity Preserved (IP) system on grain transportation in Washington by applying General Algebraic Modeling System (GAMS). I develop linear programming optimization models representing three scenarios, which are the current bulk grain transportation, the IP or containerized grain transportation and the IP system including extra material costs. The results indicate a significant change in wheat flows as a result of the IP system. The higher containerized transport rates and the prohibition of transshipment contribute to the rising transport costs. In addition, the sensitivity analysis of discounting the containerized rail rate identifies a spatial competition between the rail mode and the truck-barge mode.; The third study evaluates impacts of the Pacific Northwest (PNW) s soft white wheat (SWW) marketing plan which aims to promote wheat to buyers by providing information of the different end-use qualities of the soft white wheat grown in different geographical areas. Under this model, I assume that elevators voluntarily move grain only within the production zone and there is no grain shipment across different production zones in an attempt to preserve identity of wheat grown in a specific zone. The cost-minimizing linear programming optimization model is applied to represent elevator managers decision on grain transportation. The results indicate insignificant changes in wheat flows and a slightly increase in transport costs due to the imposition of the marketing plan. In contrast to the IP system, the zoning policy is significantly inexpensive as the result of the existing economies of scale

Effects of Thai healthcare policy on household demand, hospital efficiency and household earnings

This dissertation evaluates how healthcare and the health insurance policy in Thailand affect both supply and demand sides. This research applies different econometrics methods such as a nonparametric boostrapping Data Envelopment Analysis method, a Quadratic Almost Ideal Demand (QUAIDS) model, a random-effect Tobit regression, etc. The first chapter investigates the short-term impact of the new national health insurance program or Universal Coverage (UC) in Thailand on technical efficiency in provincial public hospitals. By measuring efficiency before and after the reform, the study applies a two-stage analysis with bootstrapping Data Envelopment Analysis (DEA) and a censored Tobit model. The results indicated that UC improved efficiency in larger public hospitals across the country. The effect differed by region around the country, and hospitals in provinces with more wealth not only started with greater efficiency, but improved their relative position after UC was implemented.; The second chapter investigates the effects of health status and healthcare utilization on agricultural household earnings in Thailand. A utility-maximization production model in which health status and education affect household resource allocation is formulated. Using the Box-Cox transformation, the 2SLS and OLS estimations are applied. A key finding indicated that education appeared to increase farm household income, while the effect from health was unclear. However, the disaggregated analysis showed that health may be a determinant to income for rice farming household in which farm income appeared to increase by 0.3% with a 10% increase in health investment.; The third chapter explores how national health insurance affects the allocation of household expenditures on consumption goods (i.e., housing, food, etc.) changed by comparing expenditure patterns before and after the health insurance reform. A Quadratic Almost Ideal Demand System (QUAIDS) model developed by Banks, Blundell, and Lewbel (1997) is used incorporating with a two-step approach introduced by Shonkwiler and Yen (1999). The programming was done on GAUSS 7.0 in order to solve the nonlinear least squares problems applying the Gauss-Newton optimization algorithm

Geo-Coding Survey Truck Route Data: GIS Analytical Applications

The application of Geographic Information Systems (GIS) has been widely accepted in a number of areas, i.e. transportation, utility network, land-use, city planning, and policy planning. Transportation policy planners and transportation network analysts, for instance, use the GIS software to analyze highway traffic and congestion problems in urban areas as well as planning for new highway infrastructure and maintenance. This paper is the first attempt in the freight transportation area to develop an automatic algorithm which allows identifying specific segments of highways used by each observed truck using the application of the GIS software. This paper utilizes data collected from the Strategic Freight Transportation Analysis (SFTA) truck survey which examined truck movements in the state of Washington. The survey includes approximately 24,000 observations of trucks traveling within (or through) the state of Washington with information on origin city and state, destination city and state, truck type, truck weight, type of commodity on board and the list of highways utilized. With known origins, destinations and the list of highways used, Arc-Info may be utilized to specifically identify unique route segments used by each truck and assign geographic attributes to the route data. Utilizing several different software features within ArcMap, including the Utility Network Analysis tool, data from a traditional relational database is input into the GIS software where several logical conditions are examined to identify unique route attributes associated with each survey response. The logical conditions examined include many attributes collected on the roadside questionnaire and help minimize error associated with the geo-coding process. This process is then automated and applied to the entire database. Many different analytical capabilities related to freight highway flows are then possible and applicable once specific routes have geographic properties, several of which are provided in this paper. These include specific highway segment properties and traffic profile, including upstream/downstream contribution of freight flows by different highways and commodities throughout the highway network