At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.
This paper proposes a clustering procedure for samples of multivariate functions in (L 2 (I)) J , with J ≥ 1. This method is based on a k-means algorithm in which the distance between the curves is measured with a metrics that generalizes the Mahalanobis distance in Hilbert spaces, considering the correlation and the variability along all the components of the functional data. The proposed procedure has been studied in simulation and compared with the k-means based on other distances typically adopted for clustering multivariate functional data. In these simulations, it is shown that the k-means algorithm with the generalized Mahalanobis distance provides the best clustering performances, both in terms of mean and standard deviation of the number of misclassified curves. Finally, the proposed method has been applied to two real cases studies, concerning ECG signals and growth curves, where the results obtained in simulation are confirmed and strengthened.
Disease progression models are a powerful tool for understanding the development of a disease, given some clinical measurements obtained from longitudinal events related to a sample of patients. These models are able to give some insights about the disease progression through the analysis of patients histories and can be also used to predict the future course of the disease for an individual. In particular, Hidden Markov Models are suitable for disease progression since they model the latent unobservable states of the disease. In this work, we propose a HMM where the outcome is multivariate and its components are not independent; to accomplish our aim, since we do not make any usual normality assumptions, we model the outcome using copulas. We first test the performance of our model in a simulation setting and show the validity of the method. Then, we study the course of Heart Failure, applying our model to an administrative dataset from Lombardia Region in Italy, showing how episodes of hospitalization can give information about the disease status of a patient.
Background and aims:We assess the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)-and telaprevir (TVR)-based TT in untreated G1CHC patients discriminated according to IL28B genotype, severity of liver fibrosis and genotype1 (G1) subtype. Methods:The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro at 2013 value), life-years gained (LYG), quality adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Cost of SOF was assumed to be D 3500 for week, i.e. the price generating a willingness-to-pay threshold of D 25,000 per LYG compared with TVR in the entire population of untreated G1 patients. The robustness of the results was evaluated by one-way deterministic and multivariable probabilistic sensitivity analyses.Results: SOF was cost-effective compared with BOC in all strategies with the exception of cirrhotic and IL28B CC patients. In comparison with TVR-based strategies, SOF was cost-effective in IL28B CT/TT (ICER per LYG D 22,229) and G1a (D 19,359) patients, not cost-effective in IL28B CC (D 45,330), fibrosis F0-F3 (D 26,444) and in cirrhotic (D 34,906) patients, and dominated in G1b patients. The models were sensitive to SOF prices and to likelihood of sustained virological response.Conclusions: In untreated G1 CHC patients, SOF-based TT may be a cost-effective alternative to first-generation Protease Inhibitors depending on pricing. The cost-effectiveness of SOF improved in IL28B CT/TT and G1a patients. SOF was dominated by TVR in G1b patients even if, in clinical practice, this issue could be counterbalanced by the good tolerability profile of SOF and by the shorter treatment duration. 5 On behalf of the WEF study group.
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