Objective: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. Methods: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). Results: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. Conclusions: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62–0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52–0.94; P = 0.018). In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas.

The purpose of this study was to evaluate the quality of life (QoL) of multiple sclerosis (MS) caregivers, and to determine relationships that may exist between caregiver and patient QoL. Patients with definite MS (n=445) and their caregivers (n=445) were required to complete the generic, 36-item short-form (SF-36) Health Survey. Median SF-36 dimension scores ranged from 55 to 100 for caregivers and from 46 to 78 for patients. Although the QoL of MS carers was not as severely affected as that of patients, caregiving was associated with lower mental health, vitality and general health scores, compared to healthy subjects. Multivariate analyses revealed significant differences between the predictors of patient QoL and caregiver QoL. The main predictors of patient QoL were Expanded Disability Status Scale (EDSS) score, MS course, fatigue and depression. Female gender and advanced age were the main predictors of lower QoL in caregivers. In addition, patient BDI score was found to be a significant predictor of almost all caregiver SF-36 dimension scores, while EDSS score, disease duration and course, and patient therapeutic characteristics were found to be predictors of some caregiver SF-36 dimension scores. Therefore, caregiver QoL was significantly influenced by patient characteristics, and supportive strategies for MS caregivers are warranted. Multiple Sclerosis 2007; 13: 412-419. http://msj.sagepub.com

Background: In 2010, the European Medicines Agency (EMA) initiated a pilot project on parallel scientific advice with Health Technology Assessment bodies (HTABs) that allows manufacturers to receive simultaneous feedback from both the European Union (EU) regulators and HTABs on their development plans for medicines.Aims: The present retrospective qualitative analysis aimed to explore how the parallel scientific advice system is working and levels of commonality between the EU regulators and HTABs, and among HTABs, when applicants obtain parallel scientific advice from both a regulatory and an HTA perspective.Methods: We analysed the minutes of discussion meetings held at the EMA between 2010, when parallel advice was launched, and 1 May 2015, when the cutoff date for data extraction was set. The analysis was based on predefined criteria and conducted at two different levels of comparison: the answers of the HTABs vs. those of the regulators, and between the answers of the participating HTA agencies.Results: The analysis was based on 31 procedures of parallel scientific advice. The level of full agreements was highest for questions on patient population (77%), while disagreements reached a peak for questions on the study comparator (30%). With regard to comparisons among HTABs, there was a high level of agreement for all domains.Conclusions: There is evident commonality, in terms of evidence requirements between the EU regulators and participating HTABs, as well as among HTABs, on most aspects of clinical development. Indeed, regardless of the question content, the analysis showed that a high level of overall agreement was reached through the process of parallel scientific advice.

Aim: The main purpose of this study was to identify each sequential phase followed by an oncology product, from European assessment until to patient access in each Italian region (IR). Methods: A panel of oncology products approved by the European Medicines Agency (EMA) in the period 2006–2008 was considered. The explored sequential phases included the times to market for: the EMA; pharmaceutical companies; the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA); and IRs as final providers of health care. The IR’s time to market was also analyzed by a Cox regression model. Results: The overall mean time required before patients access was 2.3 years. EMA accounted for the greater proportion of time (31.8%), followed by AIFA (28.2%). However, the duration for both pharmaceutical companies and IRs was associated with the highest variability. An oncology product authorized with a risk-sharing agreement showed an early access in the IRs. On the contrary, the introduction in IRs having a compulsory formulary was delayed. Both a high forecast of economic impact and a high oncology product price can also delay the patient access. Conclusion: The process before patient access to an oncology product is time and cost consuming. This study identifies the main predictors that affect the missing overlap between market and patient access in Italy.