Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Assessment of left ventricular function: visual or quantitative?

Cardiovascular Aspects of Radiolog

Quantification in cardiac MRI: advances in image acquisition and processing

Cardiac magnetic resonance (CMR) imaging enables accurate and reproducible quantification of measurements of global and regional ventricular function, blood flow, perfusion at rest and stress as well as myocardial injury. Recent advances in MR hardware and software have resulted in significant improvements in image quality and a reduction in imaging time. Methods for automated and robust assessment of the parameters of cardiac function, blood flow and morphology are being developed. This article reviews the recent advances in image acquisition and quantitative image analysis in CMR

Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps

Embodiment and Illusion: the Implications of Scale as a Cue for Immersion in Virtual Environments

This paper examines the extent to which the issue of scale impinges on our sense of immersion in virtual environments. We consider perception from the point of view of Merleau-Ponty's phenomenology, and describe a study involving extended interviews of a small number of subjects who were presented with static, moving and interactive images of spaces. We test a series of propositions about scale cues, and speculate on the wider phenomenological issues of expectation, metaphor and play. 

The INFN Treatment Planning System Project

Several technologies developed by the Italian institute of nuclear physics (INFN) for fundamental physics have been applied to medical imaging and particle therapy techniques. The partnership with leading industries has always been crucial for successful applications. Within this framework is the implementation of a Treatment Planning System (TPS) for hadrontherapy with C-ion beams, but not exclusively, in partnership with the IBA Group, with the contribution of the TPS manufacturer Elekta. Several INFN research groups that have developed competencies in different scientific areas are cooperating to the task: experimental and phenomenological nuclear physics, Monte Carlo (MC) and techniques for numerical analysis, radiobiology and hardware development for monitoring purposes. A TPS prototype is currently being studied. In order to achieve a fast plan optimization, the dose distribution is computed using look-up tables obtained from MC simulations. These are performed using Fluka and an implementation of the Local Effect Model (developed by the GSI Biophysics group). Nuclear fragmentation experiments for C-ion are now performed at the INFN???s Laboratori Nazionali del Sud (LNS) (30-80 MeV/n). Further experiments are scheduled at SIS (GSI) in the framework of the FIRST experiment (200-400 MeV/n), in collaboration with other European Institutes (GSI, ESA, CEA). Radiobiological experiments are underway at LNS and Laboratori Nazionali di Legnaro, on rodent and human cells (C-ion @ 8-80 MeV/n). Lighter ions (A = 6-12) will also be used, to reproduce the effects of fragments (up to 20 MeV/u). These experiments will provide reliable data for the validation of the simulations and for further improvements of the physical and radiobiological models to be used in the TPS

Em\u27body\u27ing Virtual Architecture: the Third International Conference of the Arab Society for Computer Aided Architectural Design

The increasing speed of technological improvements outpaced many design issues. Nowadays, architecture is accepting digital design tools and technologies as a feature integrated in design process and in spaces of our everyday “Being-in-the-World”. The consequences of this integration result in many changing and expanding forms of interaction

Towards lean premixed hydrogen combustion modelling using a data-driven approach

Lean premixed hydrogen flames are characterized by sub-unity mixture Lewis number, which causes the formation of intrinsic instabilities, driven by hydrodynamic and thermo-diffusive mechanisms that interact leading to complex corrugations of the flame front. In this contribution, an approach for lean premixed hydrogen combustion modelling is presented, based on a two-scalar manifold representation of the thermochemistry. The framework is based on a data-driven filtered tabulated chemistry approach, where a fully resolved, two-dimensional, unstable, self-wrinkling simulation is used as a source for the filtering procedure. The method is validated a-priori and a-posteriori against a two-dimensional DNS multi-step chemistry hydrogen/air dataset, consisting of statistically planar, premixed, laminar flames in rectangular computational domains periodic in the cross-wise direction