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-This paper describes the EU-funded M2DM project which is developing multi-access services for the management of diabetes mellitus. Key features of the proposed system include the merging of telemedicine with knowledge management. The issues needing to be addressed in this connection are considered, together with the setting of the project within an overall systemic, model-based framework.

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11We present a linear time-varying Luenberger observer (LTVLO) using compartmental models to estimate the unmeasurable states in patients with type 1 diabetes. The LTVLO proposed is based on the linearization in an operation point of the virtual patient (VP), where a linear time-varying system is obtained. LTVLO gains are obtained by selection of the asymptotic eigenvalues where the observability matrix is assured. The estimation of the unmeasurable variables is done using Ackermann's methodology. Additionally, it is shown the Lyapunov approach to prove the stability of the time-varying proposal. In order to evaluate the proposed methodology, we designed three experiments: A) VP obtained with the Bergman minimal model; B) VP obtained with the compartmental model presented by Hovorka in 2004; and C) real patients data set. For experiments A) and B), it is applied a meal plan to the VP, where the dynamic response of each state model is compared to the response of each variable of the time-varying observer. Once the observer is evaluated in experiment B), the proposal is applied to experiment C) with data extracted from real patients and the unmeasurable state space variables are obtained with the LTVLO. LTVLO methodology has the feature of being updated each instant of time to estimate the states under a known structure. The results are obtained using simulation with Matlab T M and Simulink T M . The LTVLO estimates the unmeasurable states from in silico patients with high accuracy by means of the update of Luenberger gains at each iteration. The accuracy of the estimated state space variables is validated through fit parameter.

Background and Objectives: The influence of smoking habits on mortality, VTE recurrence, and major bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated. Materials and Methods: We used data from the RIETE (Registro Enfermedad TromboEmbólica) registry to compare mortality, VTE recurrence, and major bleeding risk in smoking versus non-smoking patients with acute VTE. Results: 50,881 patients (43,426 non-smoking and 7455 smoking patients) were included. After a median follow-up of 8.8 months, 7110 patients died (fatal PE 292 and fatal bleeding 281), 3243 presented VTE recurrence, and 1579 had major bleeding. At multivariate analysis, smoking behavior was associated with a higher hazard of death, (HR: 1.28; 95% CI: 1.19–1.40). The risk of VTE recurrence was marginally increased in smoking patients compared to non-smoking patients (1.14; 95% CI: 1.02–1.27). Major bleeding did not differ in smoking and non-smoking patients (1.15; 95% CI: 0.96–1.38). The presence of cancer did not appear to influence the association between smoking habits and death (HR: 1.34; 95% CI: 1.22–1.47 in cancer patients and HR: 1.23; 95% CI: 1.04, 1.45 in non-cancer patients, respectively) Conclusions: the risk of death after an acute episode of VTE appeared to be higher in smoking than in non-smoking patients and this risk is higher between patients presenting PE at the onset of symptoms.