Budget impact analysis of apixaban to treat and prevent venous thromboembolism in Italy

BACKGROUND: Venous thromboembolism (VTE), a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious vascular condition associated to high economic and clinical burden. Apixaban, a Novel Oral Anticoagulant (NOAC) has shown non-inferiority efficacy versus the current standard of care (low molecular weight heparin [LMWH]/vitamin K antagonist [VKA]) in the acute treatment and prevention of VTE and a significant reduction in the risk of bleeding.AIM: Evaluate the economic impact of the use of apixaban for treatment and prevention of DVT and PE from the perspective of the Italian National Health System (NHS).METHODS: A budget impact model was adapted in order to compare clinical outcomes and economic consequences associated to apixaban vs. LMWH/VKA and others NOACs over a three-year time horizon in the Italian setting. In the analysis two scenario were compared: status quo scenario without apixaban and an alternative scenario with apixaban. Only direct healthcare costs have been considered.RESULTS: Assuming a population of patients receiving apixaban over the first 3 years equal to 20,957, the introduction of apixaban is associated to an incremental saving of € 821,748 in the first years, € 1,250,454 in the second year, and € 1,866,466 in the third year. The total net saving over the 3-year period is € 3,938,668, which is a 2.47% decrease from the total budget for the status quo scenario without apixaban. This saving is mainly due to reduced VTE events and bleeds by apixaban. Indeed apixaban is associated with less VTE events (both fatal and non-fatal), less major bleeding and less Clinical Relevant Non Major (CRNM) bleeding with a total of 52 fatal events avoided.CONCLUSIONS: The listing of apixaban for the treatment of VTE (both DVT and PE) and the prevention of recurrent VTE provides both significant clinical advantages, in terms of deaths and events avoided, and economical advantages, consisting in a reduction in the total expenditure on the Italian NHS

Fine-tuning on Clean Data for End-to-End Speech Translation: FBK @ IWSLT 2018

This paper describes FBK's submission to the end-to-end English-German speech translation task at IWSLT 2018. Our system relies on a state-of-the-art model based on LSTMs and CNNs, where the CNNs are used to reduce the temporal dimension of the audio input, which is in general much higher than machine translation input. Our model was trained only on the audio-to-text parallel data released for the task, and fine-tuned on cleaned subsets of the original training corpus. The addition of weight normalization and label smoothing improved the baseline system by 1.0 BLEU point on our validation set. The final submission also featured checkpoint averaging within a training run and ensemble decoding of models trained during multiple runs. On test data, our best single model obtained a BLEU score of 9.7, while the ensemble obtained a BLEU score of 10.24.Comment: 6 pages, 2 figures, system description at the 15th International Workshop on Spoken Language Translation (IWSLT) 201

Experimental and numerical characterization of a positive displacement vane expander with an auxiliary injection port for an ORC-based power unit

Abstract In the present work a novel technology based on a dual injection vane expander has been introduced. The component works on a power unit fed by the exhaust gases of 3L turbocharged diesel engine. The new device was tested in a wide range of operating conditions and its numerical model was validated on the experimental data. The performances of the new machine were compared to those of the original one. The results showed that the dual injection expander provided an increase of the indicated and mechanical power up to 50% and 30%. Mass flow rate can be increased by 30% and this widens the performances of the power unit; this aspect is particularly suitable for a recovery unit fed by the widely changing exhaust gases flow rates in ICEs

Effects of Oil Warm up Acceleration on the Fuel Consumption of Reciprocating Internal Combustion Engines

Abstract The homologation cycle of vehicles for private passenger transportation or for light duty applications considers a cold start from ambient temperature. The most part of harmful substances (≈ 60-65%) are produced during the thermal engine stabilization which occurs in the very of the driving cycle. This strongly influences also engine efficiency, i.e. fuel consumption. The more recent commitments on CO2, therefore, reinforce the concept of reducing warm up time encountering it in the low carbon engine technologies. Due to this importance, engine thermal management has been the subject of a huge interest opening the way to new components, technologies and control strategies. This regards not only the coolant fluid, which undoubtedly influences engine warm up, but also the lubricant:an its heating acceleration produces much faster benefits.. The purpose of this paper is to assess the effect of a faster oil heating during the homologation cycle on the fuel consumption. An experimental campaign has been done on an 3L Iveco F1C engine mounted on a dynamometer test bench operated in order to reproduce the NEDC. The engine OEM has been characterized and the effect of the oil temperature has been studied according to: (a) an external heat source which brings the oil at its stabilized temperature value before engine start, (b) an internal heat source represented by the exhaust gases which almost immediately reach a temperature value able to heat-up the oil. The effects on CO2 emissions during the cycle have been evaluated. The benefits are noteworthy and justify some oil circuit modifications

Volumetric analysis of carotid plaque components and cerebral microbleeds: a correlative study

PURPOSE: The purpose of this work was to explore the association between carotid plaque volume (total and the subcomponents) and cerebral microbleeds (CMBs). MATERIALS AND METHODS: Seventy-two consecutive (male 53; median age 64) patients were retrospectively analyzed. Carotid arteries were studied by using a 16-detector-row computed tomography scanner whereas brain was explored with a 1.5 Tesla system. CMBs were studied using a T2*-weighted gradient-recalled echo sequence. CMBs were classified as from absent (grade 1) to severe (grade 4). Component types of the carotid plaque were defined according to the following Hounsfield unit (HU) ranges: lipid less than 60 HU; fibrous tissue from 60 to 130 HU; calcification greater than 130 HU, and plaque volumes of each component were calculated. Each carotid artery was analyzed by 2 observers. RESULTS: The prevalence of CMBs was 35.3%. A statistically significant difference was observed between symptomatic (40%) and asymptomatic (11%) patients (P value = .001; OR = 6.07). Linear regression analysis demonstrated an association between the number of CMBs and the symptoms (P = .0018). Receiver operating characteristics curve analysis found an association between the carotid plaque subcomponents and CMBs (Az = .608, .621, and .615 for calcified, lipid, and mixed components, respectively), and Mann-Whitney test confirmed this association in particular for the lipid components (P value = .0267). CONCLUSIONS: Results of this study confirm the association between CMBs and symptoms and that there is an increased number of CMBs in symptomatic patients. Moreover, we found that an increased volume of the fatty component is associated with the presence and number of CMBs

charge air subcooling in a diesel engine via refrigeration unit effects on the turbocharger equilibrium

Abstract The stringent regulations on fuel saving and emissions reduction in the transportation sector have become game-raisers in the development of present internal combustion engines for road applications, even if under-the-hood space constraints, downsizing and down-weighting prevent from adopting radical changes in the engine layout. Charge air cooling is the standard in present turbocharged diesel engines, to the point that a dedicated heat exchanger, fed by environmental air, is located downstream the compressor. The paper proves the option of an additional cooling through the cabin-heating unit - usually over-sized with respect to normal operation - very effective to increase charge air density and improve cylinder filling. The intercooler downstream the compressor would be provided with a lower thermal load, hence calling for smaller heat exchange surfaces, leading to reduced weight, space saving and no increased layout complexity. By pushing this idea forward, a properly sized cabin-heating unit could even supply enough air cooling to replace the intercooler instead of just assisting it, further raising the weight/space/layout advantages. In presence of an additional heat exchanger, the cooling efficiency would be no longer related to the vehicle speed and the benefit in terms of cylinder filling could be kept to the desired value on a wider operating range for the engine. Plus, the lower combustion temperatures associated with both a colder air and a more diluted charge approaching the chamber would also result in a more regular combustion process, in spite of a moderate penalty on the thermodynamic efficiency. The additional fuel consumption to compress the cooling fluid is always offset by the fuel saving with respect to normal operation and a beneficial effect is appreciated on emissions. Nonetheless, major variables to account for when evaluating the feasibility of such a layout are (i) the impact it has on the equilibrium of the turbocharger, i.e. on the efficiency at each operating point, (ii) to what extent the presence of a colder air affects the turbine/compressor matching and (iii) the rack position the ECU fixes at the VGT, to face both pressure losses at the additional evaporator and the different enthalpy content for both the air at the compressor outlet and the exhaust gases at the turbine inlet. A comprehensive experimental activity supported by a detailed 1D model of the engine unit, aimed at assessing the benefits of the air under-cooling, allowed to select the most appropriate cooling layout and, once validated based on the experimental evidence, to investigate the equilibrium at the turbocharger

Kinematic modelling of the foot-ankle complex for gait analysis

The functional role of the foot-ankle complex is critical in terms of providing support and mobility to the whole human body. Besides those associated with common lesions or damages of its structures (e.g. sprains, bone fractures), impairments in the foot may also cause secondary chronic pathologies. Thus, a quantitative assessment of the mechanical behaviour of the joints within the foot-ankle complex is certainly of clinical value. Gait analysis is used to assess lower limb joint kinematics during walking, and is usually performed using stereophotogrammetric systems. Conventionally, the foot is considered as a rigid segment. This oversimplification has been overcome with the use of multi-segment models to describe foot kinematics. However, these models have been only partially validated, limiting their widespread adoption. This Thesis aims at filling the gap of a repeatability and reproducibility analysis of the outcomes of the available foot modelling techniques, providing guidelines and reference values to be used in future applications, and establishing a standard for the kinematic assessment of the foot-ankle complex in gait analysis. As a first step, different indices to quantify repeatability and reproducibility of model outcomes have been critically compared and investigated, including Linear Fit Method coefficients (LFM), Coefficient of Multiple Correlation (CMC), Mean Absolute Variability (MAV), and Root Mean Square Error (RMSE). A sensitivity analysis was performed to this purpose using artificially created curves, which were varied by imposing a set of realistic alterations in their shapes, joints’ range of motion, sample by sample amplitude variability, offset, and time shift. The CMC values were found to be sensible to different curve shapes, and, as well as the LFM coefficients, were independent from the range of motion. Complex values of the CMCs were observed when large offset and time shift occurred. The LFM coefficients worsened with the time shift, invalidating the assumption of linear relationship among curves. Nonetheless, these coefficients, when used with measurement of absolute differences (e.g., MAV or RMSE), were found to be the most suitable to be used for gait curve comparisons. The instrumental error associated with different procedures that can be adopted to calibrate a stereophotogrammetric system has then been assessed for two different systems. The results of this part of the Thesis showed that the errors are independent on the adopted calibration. In fact, the between-calibration CMC of joint kinematics were never lower than 0.93. The average differences between measured and known values of distances between pair of markers were lower than 1.7 mm. Instead, the average differences between measured and known values of angles between markers 0.7°. These findings suggest that relevant procedures do not affect the metrological performance of the systems under test and the associated errors can be neglected. As a following step, the experimental error associated to the marker placement was quantified for the four most adopted multi-segment models of the foot. The repeatability and reproducibility of the relative measurements were assessed by comparing joint sagittal kinematics obtained when: a) the same operator placed the markers on thirteen young healthy adults in two different sessions; b) three operators placed the markers for three times on three randomly selected participants, respectively. The two most repeatable and reproducible models, according to the validated similarity and correlation indices (i.e., the LFM coefficient), displayed averaged correlation higher than 0.72, with the lowest values obtained for the between-subject comparison of the midfoot kinematics (0.69 and 0.55). Results showed that foot kinematics have low overall repeatability when evaluated with the existing models, and normative bands should be adopted with caution when used for comparison with patient data, especially when dealing with joints that interacts with the mid-foot and display range of motions smaller than 10°. Finally, to overcome the limitations highlighted by the assessment of the existing models, a novel kinematic model of the foot-ankle complex has been designed, and the repeatability and reproducibility of the relevant sagittal kinematics have also been quantified. Results showed an improvement, especially for the joint enclosed between the mid-foot and the hindfoot, with correlation higher than 0.82. In conclusion, the new model paves the way to a more reliable modelling of the foot and, represents an improvement with respect to the existing techniques

Cost‑effectiveness analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVES: The study evaluated the cost‑effectiveness of apixaban in preventing thromboembolic events in non‑valvular atrial fibrillation (NVAF) patients, as compared to other three available novel oral anticoagulant agents (NOACs), from the Italian Health System (SSN) perspective.METHODS: A previously published lifetime Markov model was adapted for the Italian context. Baseline clinical risks were assigned based on the demographic and clinical features of the patients; effectiveness and safety parameters derived from adjusted indirect comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Expected survival was projected beyond trial duration using national mortality data adjusted for clinical risks and weighted by published utilities. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains occurring after the first year were discounted at an annual 3.5% rate. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio (ICER), where effectiveness is measured in terms of life‑years and quality adjusted life‑years gained. Deterministic and probabilistic sensitivity analyses (DSA&PSA) were carried out.RESULTS: In the short to medium term, apixaban was associated with marginal LYs and QALYs gains and slight savings, as compared to other NOACs. However, as apixaban extended expected survival versus dabigatran (110mg), dabigatran (150mg) and rivaroxaban (0.13, 0.08, and 0.06 LYs or 0.11, 0.07, and 0.05 QALYs), expected total lifetime costs exceeded those of these comparators (€ 319, € 282, and € 16). Corresponding ICERs were estimated in € 2,911, € 3,882 and € 327 per QALY gained. The most influential parameter according to DSA was daily costs of NOACs, but the corresponding ICERs remained well below commonly accepted WTP values. In PSA, the probabilities of apixaban being cost effective with a WTP threshold of 20,000 €/QALY gained were 99%, 92% and 93% for the same comparisons.CONCLUSIONS: Apixaban is expected to be more effective than dabigatran and rivaroxaban in Italian NVAF population, and marginally more costly due to consume healthcare resources for a longer period of time. The ICERs have a high likelihood of being below conventional thresholds of WTP for health benefits of the SSN and suggest that apixaban is cost‑effective compared with other three available NOACs

The economic impact associated with cerebrovascular events related to non-valvular atrial fibrillation (NVAF) in Italy: the role of apixaban

<a href="http://dx.doi.org/10.7175/fe.v15i1S.972">http://dx.doi.org/10.7175/fe.v15i1S.972</a

Budget impact analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVE: This study aims to perform a budget impact analysis of the use of three available novel oral anticoagulant agents (NOACs) for preventing thromboembolic events in Italian patients with non‑valvular atrial fibrillation (NVAF).METHODS: Estimated Italian population of patients was run through a previously published lifetime decision tree/Markov model simulating their treatment with the available therapeutic options: dabigatran at two dose levels (110 mg/bid for the over 80 years old, 150 mg/bid for younger NVAF patients), rivaroxaban (20 mg/uid), and apixaban (5 mg/bid). Effectiveness and safety estimates derive from an adjusted indirect treatment comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Epidemiological data and unit costs, actualized to 2013, are collected from Italian published sources. The budget impact analysis evaluates the financial impact of apixaban introduction by comparing expected 1,2, and 3 years costs in hypothetical scenarios: with and without apixaban. Italian NVAF patient population estimation is based on official apixaban reimbursement criteria, applying the characteristics of the trial population to national epidemiologic data. Numbers of patients for each regimen are estimated by projecting share evolution. Sensitivity analysis is performed on an alternative non‑experimental population of NVAF patients.RESULTS: Among available NOACs, apixaban was expected to be the least expensive in an estimated patient population of 364,000 Italian patients, allowing for savings of € 1,180,549, € 3,841,429 and € 5,368,918 at 1,2, and 3 years, respectively. Results of the simulation run on an alternative non‑experimental population of NVAF patients yields comparable estimates.CONCLUSIONS: The different safety and effectiveness profiles of the three available NOACs emerging from the adjusted indirect comparison indicate that apixaban could improve health care expenditure control while maintaining or increasing therapeutic appropriateness in the Italian NVAF population