Efficacy and Safety of Extracranial Vein Angioplasty in Multiple Sclerosis: A Randomized Clinical Trial.

Importance: Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by restricted venous outflow from the brain and spinal cord. Whether this condition is associated with multiple sclerosis (MS) and whether venous percutaneous transluminal angioplasty (PTA) is beneficial in persons with MS and CCSVI is controversial. Objective: To determine the efficacy and safety of venous PTA in patients with MS and CCSVI. Design, Setting, and Participants: We analyzed 177 patients with relapsing-remitting MS; 62 were ineligible, including 47 (26.6%) who did not have CCSVI on color Doppler ultrasonography screening. A total of 115 patients were recruited in the study timeframe. All patients underwent a randomized, double-blind, sham-controlled, parallel-group trial in 6 MS centers in Italy. The trial began in August 2012 and concluded in March 2016; data were analyzed from April 2016 to September 2016. The analysis was intention to treat. Interventions: Patients were randomly allocated (2:1) to either venous PTA or catheter venography without venous angioplasty (sham). Main Outcomes and Measures: Two primary end points were assessed at 12 months: (1) a composite functional measure (ie, walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity) and (2) a measure of new combined brain lesions on magnetic resonance imaging, including the proportion of lesion-free patients. Combined lesions included T1 gadolinium-enhancing lesions plus new or enlarged T2 lesions. Results: Of the included 115 patients with relapsing-remitting MS, 76 were allocated to the PTA group (45 female [59%]; mean [SD] age, 40.0 [10.3] years) and 39 to the sham group (29 female [74%]; mean [SD] age, 37.5 [10.6] years); 112 (97.4%) completed follow-up. No serious adverse events occurred. Flow restoration was achieved in 38 of 71 patients (54%) in the PTA group. The functional composite measure did not differ between the PTA and sham groups (41.7% vs 48.7%; odds ratio, 0.75; 95% CI, 0.34-1.68; P = .49). The mean (SD) number of combined lesions on magnetic resonance imaging at 6 to 12 months were 0.47 (1.19) in the PTA group vs 1.27 (2.65) in the sham group (mean ratio, 0.37; 95% CI, 0.15-0.91; P = .03: adjusted P = .09) and were 1.40 (4.21) in the PTA group vs 1.95 (3.73) in the sham group at 0 to 12 months (mean ratio, 0.72; 95% CI, 0.32-1.63; P = .45; adjusted P = .45). At follow-up after 6 to 12 months, 58 of 70 patients (83%) in the PTA group and 22 of 33 (67%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 2.64; 95% CI, 1.11-6.28; P = .03; adjusted P = .09). At 0 to 12 months, 46 of 73 patients (63.0%) in the PTA group and 18 of 37 (49%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 1.80; 95% CI, 0.81-4.01; P = .15; adjusted P = .30). Conclusion and Relevance: Venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS. Trial Registration: clinicaltrials.gov Identifier: NCT01371760.

[PRIER II. The Emilia-Romagna Research and Innovation Programme]. / PRIER II. Il Programma di Ricerca e Innovazione dell'Emilia-Romagna. I registri come strumento per il miglioramento della pratica clinica e della qualità delle cure.

The Emilia-Romagna Programme for Research and Innovation "PRIER" was born in 2005 with the aim of increasing cultural and operational conditions for the development of clinical research, useful both to the Regional Health Service (SSR) and to the private sectors of pharmaceutical and biomedical areas. In this context, the PRIER had from the beginning a double connotation: a space where the SSR can explore issues related to the development of its own research capacity; and a context where new possible ways of relating and comparison with the pharmaceutical and biomedical industry are tested. Over the years the activities of PRIER were defined by: initiatives to strengthen the system of research in SSR; development of tools to monitor activities of the research; production of clinical-organizational recommendations for the governance of innovation. In 2013 a new area of discussion and a common interest have been identified on the subject of clinical registries. In particular, it wanted to build a path of work able to identify all the possible critical and relevant points (points to consider), indispensable, necessary or useful to the construction and use of clinical registries, taking into account the points of view of all actors involved. The course began with defining the rules of the game and continued with workshops that allowed to analyse together the matter. At the end of the second workshop it was decided to make the work carried out visible: first, not to miss the opportunity offered by the past but recent discussion; secondly, to facilitate the discussion both on the issue of registers and to the adopted methodology, which sees the different actors (public and private ones) to reason together in a context for once not influenced by necessities of negotiation and government resources.

[Considerations on limits and profits of registries]. / Riflessioni e confronti sui limiti e i vantaggi dei registri.

The article collects the summary of the discussion occurred in the setting of PRIER II, in the session dedicated to the taxonomy of registries. Shown below, some specific contributions by health professionals working at the regional departments, which deal with registries, as well as the contribution on the same subject by specialists working at some pharmaceutical companies. In particular, after the presentation summarized in the article by prof. Giuseppe Costa1, the contributions, respectively by a representative of the Emilia-Romagna Region, of a health and hospital service and by the PRIER II workgroup, are following. Finally, a collective work with all participants to the working group took place to focus on all the issues considered to be crucial in defining clinical registries. At the same discussion table, institutional representatives of the regulatory national and regional branch were also invited to take into consideration the points of view of all public and private registry users, in particular in their benefits, limits and purposes. Going through the discussion on a specific check list and deepening a number of statements identified by the working group, a list of key points, essential to characterize each clinical registry, was produced.

[Considerations on what we can (and what we should not) ask to registries]. / Riflessioni e confronti su cosa possiamo (e cosa non dobbiamo) chiedere ai registri.

This article presents a summary of the discussion which took place during the works of PRIER II in the session dedicated to the methodology of registries. Following a thorough analysis of the possible methods and the limits which deal with the collection of clinical data through the registries, the different points of view were compared, perhaps the most relevant, related to this activity. All this has been done by taking advantage by the possibility to observe aspects from different points of view. In particular, the exercise considered those who have to deal with the methodological aspects of the registries as an operator of public health or as a private operator who creates services for companies. The final goal, again, was to line up a few essential points accompanied by reasoning and comments useful to anyone who wants to address the issue of registries from the methodological point of view.

Efficacy and safety of venous angioplasty of the extracranial veins for multiple sclerosis. Brave dreams study (brain venous drainage exploited against multiple sclerosis): study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a disabling progressive course. Chronic cerebrospinal venous insufficiency (CCSVI) has recently been described as a vascular condition characterized by restricted venous outflow from the brain, mainly due to blockages of the internal jugular and azygos veins. Despite a wide variability among studies, it has been found to be associated with MS. Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins. STUDY DESIGN AND METHODS: This is a multicenter, randomized, parallel group, blinded, sham-controlled trial to assess the efficacy and safety of PTA. Participants with relapsing remitting MS or secondary progressive MS and a sonographic diagnosis of CCSVI will be enrolled after providing their informed consent. Each participant will be centrally randomized to receive catheter venography and PTA or catheter venography and sham PTA. Two primary end points with respect to efficacy at 12 months are (1) a combined end point obtained through the integration of five functional indicators, walking, balance, manual dexterity, bladder control, and visual acuity, objectively measured by instruments; and (2) number of new brain lesions measured by T2-weighted MRI sequences. Secondary end points include annual relapse rate, change in Expanded Disability Status Scale score, proportion of patients with zero, one or two, or more than two relapses; fatigue; anxiety and depression; general cognitive state; memory/attention/calculus; impact of bladder incontinence; and adverse events. Six hundred seventy-nine patients will be recruited. The follow-up is scheduled at 12 months. Patients, treating neurologists, trained outcome assessors, and the statistician in charge of data analysis will be masked to the assigned treatment. DISCUSSION: The study will provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects. TRIAL REGISTRATION: Clinicaltrials.gov NCT01371760.

Methodological issues in monitoring health services and outcomes for stroke survivors: a case study.

BACKGROUND: Obtaining comprehensive health outcomes and health services utilization data on stroke patients has been difficult. This research grew out of a memorandum of understanding between the NIH and the ISS (its Italian equivalent) to foster collaborative research on rehabilitation. OBJECTIVE: The purpose of this study was to pilot a methodology using administrative data to monitor and improve health outcomes for stroke survivors in Tuscany. METHODS: This study used qualitative and quantitative methods to study health resources available to and utilized by stroke survivors during the first 12 months post-stroke in two Italian health authorities (AUSL10 and 11). Mortality rates were used as an outcome measure. RESULTS: Number of inpatient days, number of prescriptions, and prescription costs were significantly higher for patients in AUSL 10 compared to AUSL 11. There was no significant difference between mortality rates. CONCLUSION: Using administrative data to monitor process and outcomes for chronic stroke has the potential to save money and improve outcomes. However, measures of functional impairment and more sensitive outcome measures than mortality are important. Additional recommendations for enhanced data collection and reporting are discussed.