Effect of organizational features on patient satisfaction with care in Italian multiple sclerosis centres.

BACKGROUND AND PURPOSE: Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients' satisfaction with healthcare. METHODS: Eighty-one centres and 707 patients (502 women, mean age 40.5 years, SD 10.2; mean education 12.2 years, SD 3.6; time since diagnosis 5.9 years, SD 1.5) were included in the analysis. The care organization and service provided by each centre were evaluated in comparison with the National Institute for Health and Care Excellence (NICE) guidelines on management of MS. Patients' satisfaction with care was measured using the patient self-assessed questionnaire 'Comunicazione medico-paziente nella Sclerosi Multipla, revised' section 2 (COSM-R section 2). RESULTS: The clinical characteristics of patients significantly affected their satisfaction. A multivariate regression model showed that higher patients' satisfaction (COSM-R score) was inversely associated with hospital size (number of patients under care) (ß = -0.21, 95% confidence interval -0.35; -0.07) and directly associated with psychological interventions (ß = 2.44, 95% confidence interval 0.29; 4.59). CONCLUSIONS: Multiple sclerosis patients from larger hospitals are less satisfied with the information received and the relationship with HPs. Building an individualized relationship between patients and HPs and tailoring the communication of information improve patients' satisfaction. Such a goal is probably less likely to be accomplished in larger centres with many incoming patients. Moreover, when the centres also provide structured psychological interventions, the patients are more satisfied.

Emerging issues on selection criteria of levodopa carbidopa infusion therapy: considerations on outcome of 28 consecutive patients.

Many studies confirmed the efficacy and safety of continuous infusion of intrajejunal levodopa/carbidopa gel (CIILG) for advanced Parkinson's disease (PD). Although this treatment is widely used, definite inclusion/exclusion criteria do not exist. In this prospective open-label study, we evaluated the long-term outcome in 28 consecutive patients and sought to detect any predictive factor to identify the best candidates for CIILG therapy. The assessment was carried out routinely at baseline, after 6 months and every year with UPDRS III-IV, FOG Questionnaire, non-motor symptoms scale, PD questionnaire (PDQ-8), cognitive and psychiatric status evaluation (MMSE, FAB, NPI) and caregiver's quality of life. 17/28 patients reached the 24-month follow-up. A statistically significant beneficial effect was shown on motor complications in short- and long-term follow-up, also on axial symptoms like gait disturbances. A concomitant improvement in PDQ8 score was observed, with a parallel mild amelioration, but not significant, on Caregivers QoL. When classified according to their outcome on QoL, the only predictive positive factor was less severe at Neuropsychiatric Inventory (NPI) score at baseline. Considering the improvement in motor scores (duration of "off" period), the more advanced age was associated with a poorer outcome. Our results confirmed a sustained efficacy and safety in long-term follow-up and suggest that younger age at operation and absence or mild presence of psychiatric/behavioural symptoms could be considered valid predicting factors in selecting the best candidates for this efficacious therapy.

Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of 462 cases.

Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI. The objective of the study is to evaluate the outcome and safety of ET in Italian MS patients. Italian MS centers that are part of the Italian MS Study Group were all invited to participate to this retrospective study. A structured questionnaire was used to collect detailed clinical data before and after the ET. Data from 462 patients were collected in 33 centers. ET consisted of balloon dilatation (93 % of cases) or stent application. The mean follow-up duration after ET was 31 weeks. Mean EDSS remained unchanged after ET (5.2 vs. 4.9), 144 relapses occurred in 98/462 cases (21 %), mainly in RR-MS patients. Fifteen severe adverse events were recorded in 3.2 % of cases. Given the risk of severe adverse events and the lack of objective beneficial effects, our findings confirm that at present ET should not be recommended to patients with MS.

Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience.

BACKGROUND: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. OBJECTIVES: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. METHODS: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months. RESULTS: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. CONCLUSIONS: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

Quality of life, depression and fatigue in mildly disabled patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study.

BACKGROUND: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. OBJECTIVE: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. METHODS: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing-remitting MS treated with subcutaneous interferon beta-1a. RESULTS: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low (<30) at all time points. CONCLUSION: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found.

Natalizumab therapy of multiple sclerosis: recommendations of the Multiple Sclerosis Study Group--Italian Neurological Society.

Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.

Three years of experience: the Italian registry and safety data update.

At the end of 2006, a pharmacovigilance program on natalizumab was settled by the Italian Pharmaceutical Agency, and on January 2007, multiple sclerosis patients poorly responding to the immunomodulating therapies or with an aggressive clinical form of disease from onset initiated to be registered and to receive the medication. On February 2010, almost 3,000 cases have been treated with natalizumab. The drop-out rate is 10%. Almost 800 cases received cycles of natalizumab for more than 18 months. One case of PML was reported and other adverse events are similar to those described in phase III studies. The majority of cases remained stable, while in 25% of cases, an improvement of disability was documented.

Effects of immunomodulatory treatment with subcutaneous interferon beta-1a on cognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis.

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score

The interleukin-1 cluster gene region is associated with multiple sclerosis in an Italian Caucasian population.

BACKGROUND: Polymorphisms of the interleukin-1 (IL-1) gene family have been proposed as potential variants for different diseases including multiple sclerosis (MS). With respect to MS, IL-1 beta (-511 C/T; rs16944), IL-1 beta (+3954 C/T; rs1143634), IL-1 alpha (-889 C/T; rs1800587), IL-1 alpha (+4845 G/T; rs17561), and the variable number of tandem repeats in intron 2 of the IL-1 receptor antagonist (IL-1RN) gene polymorphisms have been studied in different ethnic groups, leading to conflicting results. METHODS: This study investigates the association between IL-1 genes and MS by means of 70 markers spanning the 1.1 Mb region where the IL-1 genes map and exploring both the linkage disequilibrium (LD) and the haplotype structure in a case-control design including 410 subjects (160 patients and 250 controls). RESULTS: From allelic/genotypic tests, significant association was found for several polymorphisms including the IL-1 beta (-511 C/T) variant (P-adjusted = 4.5 x 10(-4)) and some polymorphisms around the IL-1RN gene. The 'block-step' pattern obtained from both the LD map and pairwise analysis identifies four LD regions. Region 1 showed a significant association with MS for the global test (P < 0.0001) and haplotypes containing the IL-1 beta (-511 C/T) variant still demonstrate highly significant association with disease (P-value range: 9.9 x 10(-5) to 0.02). CONCLUSIONS: Our findings support the existence of a causative variant for MS within this candidate region in a representative Italian Caucasian population and, in particular, the role of the IL-1 beta (-511 C/T) variant warrants further investigation.

The pharmacovigilance program on natalizumab in Italy: 2 years of experience.

At the end of 2006 a country-based surveillance program on natalizumab therapy in multiple sclerosis was settled in Italy by a collaborative effort of the Italian Drug Agency (AIFA) and a group of experts and neurologists appointed by the National Society of Neurology (SIN). After 2 years, 1,818 patients are registered in the database. The majority of cases (88.6%) failed the therapy with beta interferon or glatiramer acetate and had relapses or accumulated disability during immunomodulating treatment, while 11.4% of patients enrolled in the surveillance study were not previously treated with immunomodulating therapies and had a rapidly evolving clinical course. Almost 10% of the patients treated with natalizumab interrupted, for various different reasons, the therapy. Treatment was well tolerated and side effects were similar to those reported in the registrative studies. The majority of treated cases are stable or ameliorated.

Multiple sclerosis in the province of Ferrara : evidence for an increasing trend.

BACKGROUND: Epidemiological studies on the distribution of multiple sclerosis (MS) conducted in the Mediterranean area in the last two decades have disclosed a significant increase in frequency of the disease, indicating caution when a latitude-related model of MS is accepted. Previous descriptive surveys in the province of Ferrara, northern Italy, carried out by our own epidemiological research group, have established that this area is at high risk for MS. OBJECTIVE: To confirm the above assumption and to update MS frequency estimates in this area. DESIGN AND SETTING: We conducted a community-based intensive prevalence and incidence study, by adopting a complete enumeration approach. RESULTS: On December 31, 2004, 423 patients (300 women and 123 men) suffering from definite or probable MS (Poser's criteria) living in the province of Ferrara, yielded a crude prevalence rate of 120.93 (95 % CI, 110.05-134.23) per 100,000, 164.26 for women and 73.59 for men. The average incidence from 1990 to 2003 was 4.35 per 100,000 (95 % CI, 3.77-4.99), 5.91 for women and 2.63 for men. The incidence rate,which was relatively stable during the previous 25 years (1965-1989) with a mean rate of 2.3 per 100,000, increased to a value of 3.39 per 100,000 in the period 1990-1994, 4.09 per 100,000 in the period 1995-1999 and 3.84 per 100,000 in the period 2000-2003. CONCLUSIONS: These results confirm that in Ferrara MS occurs more frequently than suggested by the geographic- related distribution model and, based on other recent national surveys, support the view that northern Italy is a high-risk area for the disease. The marked increase in MS prevalence rate, in comparison with previous investigations, is in part due to the increasing survival of patients as a result of improved supportive care and the accumulation of new incidence cases owing to the reduction in diagnostic latency for better quality of neurological diagnostic procedures. The incidence in the province of Ferrara was found to slowly change with an incremental trend,which cannot only be attributed to improvements in diagnostic ability. Environmental risk factors in genetically predisposed people over time could be considered.

Multiple sclerosis in Italy. A reappraisal of incidence and prevalence in Ferrara.

BACKGROUND: Previous descriptive surveys on multiple sclerosis (MS) in the province of Ferrara, northern Italy, carried out by our own epidemiological research group, pointed out that this area was not at low-medium risk for MS. OBJECTIVE: To verify the morbidity estimates and update the temporal trend of MS. DESIGN AND METHODS: We used a complete enumeration approach by reviewing all the possible sources of case collection available in Ferrara for 1965 through 1993. We included all patients with definite and probable MS according to the criteria of Poser et al. RESULTS: The mean annual incidence rate was 2.3 per 100,000 population (95% confidence interval, 2.0-2.6 per 100,000), 3.0 per 100,000 for women and 1.5 per 100,000 for men. On December 31, 1993, 249 patients (170 women and 79 men) suffering from definite or probable MS were living in the province of Ferrara, giving a crude prevalence rate per 100,000 population of 69.4 (95% confidence interval, 61.2-78.7), 90.8 for women and 46.0 for men. CONCLUSION: The data confirm that in Ferrara, MS occurs more frequently than previously suggested by the latitude-related epidemiological model, supporting the view that northern Italy is a high-risk area for the disease. While the prevalence rate is much higher than in our previous studies, probably owing to the increasing survival of the patients because of improving supportive care, the incidence rates, similar in magnitude to those observed in high-risk areas of northern and central Europe, have remained relatively stable over time.

Parkinson's disease in Ferrara, Italy, 1967 through 1987.

Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type.

The increasing incidence and prevalence of MS in a Sardinian province.

OBJECTIVE: To verify incidence rates and their temporal trend in a homogeneous, ethnically, and genetically distinct population of central Sardinia (the Nuoro province). BACKGROUND: Intensive epidemiologic studies carried out in Sardinia since the 1970s have suggested that the prevalence and incidence of MS are much higher in this Mediterranean island compared with those found on mainland Italy. METHODS: The study area had a population of approximately 274, 000 people in the 1991 census. The authors adopted a complete enumerative approach by reviewing all possible sources of case collection available in the investigative area. RESULTS: Based on 469 MS patients, the mean annual incidence for 1955 to 1995 was 4.18 per 100,000 (or 4.3 per 100,000 if age- and sex-adjusted to the European population). The incidence, averaging 1.95 per 100,000 during 1955 to 1959, rose progressively over time, reaching rates of 6.6 in the quinquiennium 1985 to 1989 and 6.4 per 100,000 in 1990 to 1995. On December 31, 1994, the crude prevalence, based on 415 MS patients alive in the study area, was 151.9 per 100,000 (156.6 if adjusted to the European population). CONCLUSION: These incidence and prevalence rates are the highest to date that have been estimated for a large community in southern Europe, and they constitute some of the highest rates in the world. Based on other surveys, these results reinforce the position of Sardinia as a higher and rising prevalence area for MS compared with other Mediterranean populations. Genetic and social-historic data strengthen the hypothesis of the environmental role and genetic factors among Sardinians in determining the notable difference in MS frequency between Sardinians and other Mediterraneans.

The frequency of clinical variants of Guillain-Barré syndrome in Ferrara, Italy.

As the available diagnostic criteria (National Institute of Neurological and Communicative Disorders and Stroke, NINCDS) for Guillain-Barré syndrome (GBS) do not permit inclusion of clinical variants (CV) of GBS, there are few data on their occurrence and few reports of the overall incidence of the disease. A population-based study in the local health district of Ferrara, Italy in 1981-1993 selected cases fulfilling both NINCDS criteria (NINCDS GBS cases) and CV. The incidence of CV was 0.35 per 100,000 person-years (95% CI: 0.15-0.68), 0.32 when age-adjusted to the Italian population. No difference was found between CV and NINCDS GBS for male/female ratio, mean age at onset, elevated CSF protein content, seasonal pattern, or mean time delay from first neurological symptom to maximal severity. A higher frequency of antecedent infections for CV and more frequent serious disease at the nadir time for NINCDS GBS were found. A complete recovery was more frequent for CV than NINCDS GBS, but no difference was found regarding good outcome (defined by a satisfactory recovery and resumption of normal functional life). Since most findings were similar for NINCDS GBS and CV cases, they may have similar underlying pathological mechanisms. When diagnostic criteria for GBS include CV, the overall disease incidence in the Ferrara district increases from 1.87 to 2.21 cases per 100,000 person-years (the contribution of CV to the overall incidence of GBS is 15.7%). The currently available diagnostic criteria for GBS, although useful for field studies, may be too restrictive as they can entail the loss of about 15% of cases.

Epidemiological study of myasthenia gravis in the province of Ferrara, Italy.

The only prevalence rate of myasthenia gravis (MG) so far estimated in Italy by an epidemiological study carried out in Pavia, North Italy, indicates a prevalence quite similar to that observed in other countries. The purpose of the survey was to verify the frequency of the disease in a geographically well-defined and previously surveyed community. On the basis of 39 cases, on 31 December 1987 the prevalence per million was 105.3 (102.3 if standardized for the Italian population). This is the highest prevalence figure yet found, indicating a value similar to that established in Northern Europe. According to Kurtzke this high prevalence rate reflects the high standard of the local public health service, which permitted a more intensive search for affected subjects.

Predisposing factors in Bell's palsy: a case-control study.

The frequency of diabetes mellitus reported in subjects affected by Bell's palsy varies widely. In this investigation, a case-control study, we encountered a frequency of 24.8%. In addition, arterial hypertension and lipid disturbances were found to affect subjects with Bell's palsy more frequently than controls. These findings appear to suggest a primarily ischaemic pathogenesis for most cases of idiopathic peripheral facial paralysis. Furthermore, the finding of significantly lower taste impairment in diabetics than in non-diabetics with Bell's palsy may support the hypothesis of a vascular rather than a metabolic pathogenesis in these cases also. In fact, the vessels supplying the distal portion of the facial nerve, probably more affected in the diabetic patients in order to preserve taste sensation, have such a particular anatomical configuration that this might favour the onset of a diabetic small vessel disease which, in turn, would represent a factor of easier decompensation.

Systemic lupus erythematosus presenting with neurological disorders.

Six patients are described who developed a wide variety of neurological manifestations heralding systemic lupus erythematosus (SLE), which included epileptic seizures, stroke, peripheral polyradiculoneuropathy similar to Guillain-Barré syndrome, transverse myelopathy and multifocal disorders with remitting course mimicking multiple sclerosis. The peculiarity of these cases was that the neurological disorders remained the only manifestations of SLE for many years and the nervous system appeared to be the main target even after the development of systemic SLE. In five patients the prognosis was favourable and corticosteroid treatment led to prolonged remission.

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE: To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS: In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS: Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS: In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.