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Background: The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients., Methods: We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis., Results: During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07-2.41, p<0.001) and a lower baseline NRS score (adjHR 0.51 95% CI 0.46-0.56, p<0.001) were predictive of treatment discontinuation., Conclusion: These data show that the first 6 weeks are useful in identifying those patients in which Sativex could be effective, thus avoiding the cost of longer term evaluation.

Leaf hydraulic conductance (K(leaf) ) and vulnerability constrain plant productivity, but no clear trade-off between these fundamental functional traits has emerged in previous studies. We measured K(leaf) on a leaf area (K(leaf&#95;area)) and mass basis (K(leaf&#95;mass)) in six woody angiosperms, and compared these values with species' distribution and leaf tolerance to dehydration in terms of P(50), that is, the leaf water potential inducing 50% loss of K(leaf) . We also measured several morphological and anatomical traits associated with carbon investment in leaf construction and water transport efficiency. Clear relationships emerged between K(leaf&#95;mass), P(50), and leaf mass per unit area (LMA), suggesting that increased tolerance to hydraulic dysfunction implies increased carbon costs for leaf construction and water use. Low P(50) values were associated with narrower and denser vein conduits, increased thickness of conduit walls, and increased vein density. This, in turn, was associated with reduced leaf surface area. Leaf P(50) was closely associated with plants' distribution over a narrow geographical range, suggesting that this parameter contributes to shaping vegetation features. Our data also highlight the carbon costs likely to be associated with increased leaf tolerance to hydraulic dysfunction, which confers on some species the ability to thrive under reduced water availability but decreases their competitiveness in high-resource habitats., (© 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.)