A. Solari

Computer-aided retraining of memory and attention in people with multiple sclerosis: A randomized, double-blind controlled trial

CONTEXTnCognitive compromise is one of the main contributing factors to activity and participation restrictions in people with multiple sclerosis (MS). Computer-aided programs are used for retraining memory and attention, but data on the efficacy of these interventions are scarce.nnnOBJECTIVEnTo assess the efficacy of computer-aided retraining of memory and attention in people with MS impaired in these abilities.nnnDESIGN AND SETTINGnRandomized, double-blind, controlled trial.nnnPARTICIPANTSnOutpatients (n=82) with subjective complaints of poor attention or memory, confirmed by a score <80th percentile in at least two tests of the Brief Repeatable Battery of Neuropsychological Tests (BRBNT).nnnINTERVENTIONSnParticipants were randomized to two computer-assisted retraining interventions: memory and attention (study arm), and visuo-constructional and visuo-motor coordination (control arm). Both groups received 16 training sessions over 8 weeks.nnnOUTCOME MEASURESnImprovement of 20% or more in at least two BRBNT test scores at 8 weeks compared to baseline (primary end point). Changes in depression and health-related quality of life.nnnRESULTSnAn improvement occurred in 45% of study patients vs. 43% of control patients (odds ratio 1.07, 95% confidence interval 0.44-2.64). The study treatment was better than the control treatment only on the word list generation test (p=0.016).nnnCONCLUSIONSnThis trial does not support the efficacy of specific memory and attention retraining in MS.

Natalizumab for relapsing remitting multiple sclerosis

BACKGROUNDnNatalizumab (NTZ) (Tysabri(®)) is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier, thus reducing inflammation in central nervous system, andxa0has been approved worldwidexa0for the treatment of relapsing-remitting multiple sclerosis (RRMS).nnnOBJECTIVESnTo evaluate the efficacy, tolerability and safety of NTZ in the treatment of patients with RRMS.nnnSEARCH STRATEGYnWe searched the Cochrane Multiple Sclerosis Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2010, Issue 1), MEDLINE (PubMed) and EMBASE, all up to 19 February 2010, and bibliographies of papers. Handsearching was carried out. Trialists and pharmaceutical companies were contacted. Furthermore, the websites of US Food and Drug Administration (FDA), the European Medicines Evaluation Agency (EMA) and the National Institute for health and Clinical Excellence (NICE) were also checked.nnnSELECTION CRITERIAnAll double-blind, randomised, controlled trials analysing more than a single infusion of NTZ (dosage > 3 mg/kg intravenous infusion every 4 weeks), also including its use as add-on treatment, versus placebo or other drugs in patients with RRMS. No restrictions on the basis of duration of treatment or length of follow up.nnnDATA COLLECTION AND ANALYSISnThree reviewers independently selectedxa0articles which met the inclusion criteria. Disagreements were solved by discussion. Two reviewers independently extracted the data and assessed the methodological quality of each trial. Missing data was sought by contacting principal authors and Biogen Idec, through Biogen-Dompé Italia.nnnMAIN RESULTSnThreexa0studies met the inclusion criteria. These included one placebo-controlled trial (942 patients) and twoxa0add-on placebo-controlled trials, i.e. one plus glatiramer acetate (110 patients) and the second plus interferon beta-1a (1171 patients).This review assessed the efficacy, tolerability and safety of NTZ in patients with RRMS. Data was conclusive with respect to efficacy and tolerability, but not safety. As far as efficacy is concerned, the results showed statistically significant evidence in favour of NTZ for all the primary outcomes and for the secondary ones where data was available. NTZ reduced the risk of experiencing at least one new exacerbation at 2 years by about 40% and of experiencing progression at 2 years by about 25% as compared to a control group. MRI parameters showed statistical evidence in favour of participants receiving NTZ. Infusion reactions, anxiety, sinus congestion, lower limb swelling, rigors, vaginitis and menstrual disorders were reported as adverse events (AEs) more frequently after NTZ treatment. In this review NTZ was found to be well tolerated over a follow-up period of two years: the number of patients experiencing at least one AE (including severe and serious AEs) during this period did not differ between NTZ-treated patients and controls. Safety concerns have been raised about Progressive Multifocal Leukoencephalopathy (PML). In the trials included in this review, two cases of PML were encountered: one in a patient who had received 29 doses of NTZ and a second fatal case of PML in another patient after 37 doses of NTZ. Our protocol was insufficient to evaluate PML risk as well as other rare and long-term adverse events such as cancers and other opportunistic infections, which are very important issues in considering the risk/benefit ratio of NTZ.nnnAUTHORS CONCLUSIONSnAlthough one trial did not contribute to efficacy results due to its duration, we found robust evidence in favour of a reduction in relapses and disability at 2 years in RRMS patients treated with NTZ. The drug was well tolerated. There are current significant safety concerns due to reporting of an increasing number of PML cases in patients treated with NTZ. This review was unable to provide an up-to-date systematic assessment of the risk due to the maximum 2 year-duration of the trials included. An independent systematic review of the safety profile of NTZ is warranted. NTZ should be used only by skilled neurologists in MS centres under surveillance programs.All the data in this review came from trials supported by the Pharmaceutical Industry. In agreement with the Cochrane Collaboration policy, this may be considered a potential source of bias.

Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis.

Abstract.Depression is the commonest psychiatric disturbance innpeople with multiple sclerosis (MS), with prevalence higher thannin the general population and other chronic diseases. However,naccurate assessment of depressive symptoms can be biased bynsomatic symptoms which are part of both MS and depression. Wentranslated and adapted into Italian the Chicago multiscalendepression inventory (CMDI) and assessed its acceptability,ninternal consistency and test-retest reliability in 213 MSnoutpatients and 213 individually matched healthy controls. Thenquestionnaire was also tested in 32 people with majorndepression. Acceptability, internal consistency, and test-retestnreliability were good overall. We found greater odds forndepressive symptoms in people with MS than healthy controls,nwith highest odds ratio for somatic symptoms (vegetativensubscale). The Italian CMDI is characterized by goodnacceptability, internal consistency, and testretest reliability.nThese findings support the use of the CMDI in Italian subjectsnwith MS to screen for and follow depressive symptoms.

Aminopyridines for symptomatic treatment in multiple sclerosis.

BACKGROUNDnThe potassium channel blockers 4-aminopyridine (AP) and 3,4-diaminopyridine (DAP) increase nerve conduction in demyelinated nerve fibers, and have been proposed as a symptomatic therapy for people with multiple sclerosis (MS).nnnOBJECTIVESnTo determine the efficacy and safety of aminopyridines for neurological deficits in MS people.nnnSEARCH STRATEGYnWe searched CENTRAL (Issue 2, 2002), MEDLINE (January 1966-July 2002), EMBASE (1974-July 2002), and the Cochrane MS Groups Specialised Register. We hand searched bibliographic references from retrieved studies and recent MS symposia reports, and contacted known studies investigators.nnnSELECTION CRITERIAnWe included trials fulfilling all following criteria: randomised controlled trials (RCTs); adults with MS, out of exacerbation; AP or DAP treatment versus placebo; clinical endpoints.nnnDATA COLLECTION AND ANALYSISnWe identified 26 potentially pertinent studies. Three reviewers independently extracted data and assessed trial quality from 17 full-paper studies.nnnMAIN RESULTSnSix studies (eight publications, 198 participants, all crossover trials) were considered. Five studies assessed the efficacy of AP versus placebo, one compared DAP with active placebo. Treatment duration ranged from hours to six months. Median quality score of the studies was 3. Heterogeneity of outcome assessment and absence of information on individual study periods allowed quantitative pooling of results for few categorical variables. Of the 198 treated patients, there were six major side effects: one acute encephalopathy, three episodes of confusion, and two seizures. Three studies (54 patients) assessed manual muscle testing, with 29 patients (54%) improving in at least one muscular district during study treatment versus four patients (7%) during placebo (odds ratio [OR] 14.5, 95% confidence interval [CI] 4.7-43.7). Nine out of 54 participants (17%) improved in ambulation during study treatment versus none during placebo (p<0.001). A lower EDSS score was found in 13/198 participants during study treatment (7%) versus none during placebo (p<0.001). No improvement in neuropsychological tests was found in three trials assessing cognitive function. Finally, 47/136 MS people (35%) felt better when receiving the study drug, against 7(5%) on placebo (OR 9.7, 95% CI 4.3-22.0).nnnREVIEWERS CONCLUSIONSnCurrently available information allows no unbiased statement about safety or efficacy of aminopyridines for treating MS symptoms. Furthermore, we could not obtain any data on three unpublished RCTs (more than 300 participants). We conclude that publication bias remains a pervasive problem in this area, and that until the results of these unpublished studies are available to the scientific community, no confident estimate of effectiveness of aminopyridines in the management of MS symptoms is possible.

Comparison of two brief neuropsychological batteries in people with multiple sclerosis

Background: We compared two brief neuropsychological batteries devised to assess people with multiple sclerosis (MS) and used them to assess the relationship between cognitive impairment and clinical characteristics. Methods: We administered either the Brief Repeatable Battery of Neuropsychological Tests (BRBNT) or the Screening Examination for Cognitive Impairment (SEFCI) to 213 consecutive MS outpatients and 213 individually matched controls. Results: Administration times were longer for BRBNT than SEFCI, for MS and controls (p=0.001). People with MS had lower scores in all individual tests than controls (p<0.001, BRBNT and SEFCI). By the criterion of poor performance on one or more tests, the sensitivity of BRBNT was 41.9% and that of SEFCI 31.5%. The corresponding figures by poor performance on two or more tests were 16.2% for BRBNT and 18.5% for SEFCI. The Buschke Selective Reminding and Paced Auditory Serial Addition were the tests best discriminating between people with MS and controls for BRBNT, and the Symbol Digit Modalities test for SEFCI. The only clinical variable independently associated with impaired performance on these batteries was EDSS. Conclusions: Both cognitive batteries were well accepted and easy to administer. Administration time for SEFCI was significantly shorter than for BRBNT; however, alternative forms for serial evaluation are available only for BRBNT. The BRBNT was slightly more sensitive in detecting impairment by the criterion of poor performance on one or more tests. EDSS score was the only clinical variable independently associated with cognitive impairment.

Communicating the diagnosis of multiple sclerosis - a qualitative study

Studies on communicating the diagnosis of multiple sclerosis (MS) are few, and all reveal communication and information deficits. We explored the personal experience of diagnosis communication of people with MS and health professionals, using a qualitative methodology. Data were obtained from two sets of focus group meetings (FGM) with people with MS (total 23; 16 females; age range: 23-70) and one FGMs with health professionals (four neurologists, three psychologists, two nurses). The methods of framework analysis were applied to meeting transcripts to identify key topics and categories. The experience of communicating/receiving an MS diagnosis was highly varied; all patients reported the moment as powerfully evocative and unforgettable. Very poor levels of support and information were sometimes given. Although diagnosis communication had improved in more recent experience, all felt it should be further improved with appropriate setting (privacy, no interruptions, sufficient time), information tailored to the individual, and continuity of care. Such improvements imply a more meaningful patientneurologist relationship, and also structural and organisational changes. Multiple Sclerosis 2007; 13: 763-769. http://msj.sagepub.com

An information aid for newly diagnosed multiple sclerosis patients improves disease knowledge and satisfaction with care

Background: Patients report information deficits in the period surrounding diagnosis of multiple sclerosis (MS). We assessed the effectiveness of an add-on information aid for newly diagnosed MS patients. Methods: We randomly assigned 120 newly diagnosed MS patients from five Italian centres to diagnosis disclosure (current practice at the centre) or current practice plus information aid (ISRCTN81072971). The information aid consisted of a personal interview with a physician using a navigable compact disc and a take-home booklet. The primary composite endpoint was score in the highest tertile of MS knowledge and satisfaction with care questionnaires. Other endpoints were safety; treatment adherence; extra contacts/consultations; switching of care centre; and changes in Hospital Anxiety and Depression Scale and Control Preference Scale scores. Results: At 1 month, 30/60 intervention and 8/60 control patients achieved the primary endpoint (odds ratio [OR] 6.5, 95% CI 2.6—16.0; p < 0.001; number needed to treat [NNT] 3). Figures at 6 months were 26/60 intervention and 11/60 control patients (OR 3.4, 95% CI 1.5—7.8; p = 0.04; NNT 4). There were no adverse events. No significant treatment effects were seen on secondary outcomes. Conclusion: The information aid was safe and significantly associated with attainment of the primary outcome at 1 and 6 months.

Participation in medical decision-making: Attitudes of Italians with multiple sclerosis

BACKGROUNDnPatient involvement in decisions regarding their care has been advocated, but preferences have not been adequately canvassed, particularly in people with multiple sclerosis (MS).nnnOBJECTIVESnTo cross-culturally adapt and validate the Italian version of the Control Preference Scale (CPS) subsequently used to assess preferences of people with MS.nnnMETHODSnTranslation-adaptation into Italian of CPS from the original Canadian English followed by administration in 140 people with MS from five Italian centers (with re-administration in 35) and semi-structured interview.nnnRESULTSnCross-cultural adaptation of CPS was successful. The 140 people with MS, who varied in clinical and general characteristics, considered the CPS clear and acceptable. Test-retest reliability was moderate (weighted Kappa 0.65; p<0.001). A collaborative role was preferred (61%), followed by passive (33%) and active (6%) roles. Education (odds ratio [OR] 2.43, 95% confidence limits [CI] 1.05-5.66) and length of follow-up at referral center (OR 0.36, 95% CI 0.14-0.92) were associated with choice of an active/collaborative role in the logistic model.nnnCONCLUSIONSnThe Italian CPS was well accepted by our MS population. Our data indicate that a high proportion of Italians with MS prefer a more passive role and this should be considered during the clinical encounter.

General practitioners facing dementia: are they fully prepared?

Abstract.We assessed knowledge about Alzheimer’s disease (AD) in ansample of Italian general practitioners (GPs). We first carriednout a propedeutic study to verify the ability of an Italiannversion of the University of Alabama at Birmingham’s ADnKnowledge Test for Health Professionals to distinguish betweenn20 AD specialists and 20 non-specialists and to gain referencenvalues. We then administered the test, together with a shortnquestionnaire, to 139 GPs attending an educational programme innNovember 2000. The cut-off score for discriminating specialistsnfrom non-specialists was ≥9. Among the 95 GPs who performed thenAD Knowledge Test (68.3% response rate), 21% had a total scoren≥9. Our findings suggest that particular focus should be givennto dementia in continuing medical education (CME) programmes fornGPs.

The Multiple Sclerosis Knowledge Questionnaire: a self-administered instrument for recently diagnosed patients.

There are few studies on patient knowledge in multiple sclerosis (MS), and only two published questionnaires. The objective of this article was to develop and validate the MS Knowledge Questionnaire (MSKQ), a self-assessed instrument for newly diagnosed MS patients. Thirty multiple-choice statements, conceived to test MS knowledge, were produced by a multidisciplinary panel and pre-tested on three MS patients, resulting in an intermediate 26-item version. This was tested on 54 MS patients for internal consistency, content and construct validity (validation sample I). The final (25-item) MSKQ was a primary outcome measure in the SIMS-Trial on an information aid to newly diagnosed MS patients. Postal responses of SIMS-Trial participants to the MSKQ a month after intervention (validation sample II) were analysed. Median MSKQ scores in validation samples I and II were, respectively, 18 (range 9—23) and 17 (range 3—24). Acceptability, internal consistency (Kuder—Richardson-20 formula 0.76) and content validity were good. Educational attainment and receiving the information aid were the main independent predictors of MS knowledge. Other predictors were female sex (positive association) and disease duration (negative association). In conclusion, the MSKQ has good clinimetric properties and is sensitive to an educational intervention. We propose the MSKQ as a brief instrument for clinical practice and research.