Extended outpatient rehabilitation: its influence on symptom frequency, fatigue, and functional status for persons with progressive multiple sclerosis. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter Phase III study. Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group. Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients--a randomised controlled trial. Effectiveness of rehabilitation intervention in persons with multiple sclerosis: a randomised controlled trial. Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial. Evaluation of a MS specialist nurse programme. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis.
To determine the influence of an extended outpatient rehabilitation program on symptom frequency, fatigue, and functional status for persons with multiple sclerosis (MS).
                Nonequivalent pretest/posttest control-group design, with posttest 1 year after initial assessment. Multiple regression analysis and analysis of covariance were used to control for symptom severity at the initial assessment and comorbid factors including depression, cognitive function, and social interaction. Effect sizes (ES) provided a descriptive measure of the change in outcomes.
                Outpatient multidisciplinary rehabilitation clinic.
                Forty-six patients with definite chronic progressive MS; 20 received treatment and 26 were in a nontreatment comparison group ("waiting list").
                Rehabilitation services for 5 hours, 1 day per week, over 1 year.
                The MS-Related Symptom Checklist composite score, fatigue frequency, and selected items from the Rehabilitation Institute of Chicago Functional Assessment Scale.
                Receiving treatment was a significant predictor of reduced symptom frequency (partial r2 = .26) at the 1-year follow-up. The ES adjusted for baseline values indicated substantial reductions in symptom frequency for the treatment group (EStreatment = .27 vs ESwaitlist = -.32). Fatigue was significantly reduced at the time of follow-up for the treatment group compared with the waiting list group (EStreatment = .46 vs ESwaitlist = -.20). There were no statistically significant differences among groups regarding functional status, but there appeared to be less loss of functional status in the treatment group compared with the waiting list group (EStreatment = -.07 vs ESwaitlist = -.70).
                An extended outpatient rehabilitation program for persons with definite progressive MS appears to effectively reduce fatigue and the severity of other symptoms associated with MS. To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx.
                Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a "biphasic concomitant boost" schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis.
                From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% +/- 4% for CF and 78% +/- 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% +/- 5% for CF and 64% +/- 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% +/- 4% and 27% +/- 6% for CF and AF, respectively (p = 0.10).
                Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection; however, AF might be an option for patients who delay starting RT. The value of a short course of intensive immunosuppression with cyclophosphamide in stabilising chronic progressive multiple sclerosis (MS) was examined in a randomised single-blinded, placebo-controlled clinical trial. Forty two patients, from the Kaiser Permanente Medical Care Program, Northern California, were studied. Twenty two patients received a short course of cyclophosphamide in an outpatient neurology clinic until their leucocyte counts fell below 4000/mm3, and 20 patients received folic acid. Level of disability, impairment of functional systems, and performance of social roles were assessed before randomisation and reassessed 12, 18, and 24 months after therapy. In both the cyclophosphamide and folic acid groups, the mean level of disability increased from the baseline examination to the 12 month follow up examination (the primary endpoint) by 0.5 on Kurtzke's Expanded Disability Status Scale, indicating similar disease progression in the two groups. Although immunosuppression therapy can be safely administered to MS patients in an outpatient clinic, evidence of substantial benefits was not found. Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double-blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo-treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant. It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS. A stratified, randomised, waitlist controlled study over 12 months assessed the effectiveness of rehabilitation in persons with multiple sclerosis (MS) in an Australian community cohort.
                Patients with definite MS (n = 101) recruited from a tertiary hospital database, randomised to a treatment group (n = 49) for individualised rehabilitation programme or a control waitlist group (n = 52). Functional Independence Measure (FIM) was used to assess "activity" while the Multiple Sclerosis Impact Scale (MSIS-29) and General Health Questionnaire (GHQ-28) assessed "participation" and quality of life (QoL). Assessments were at baseline and 12 months.
                Analysis of data from 98 patients (treatment n = 48, control n = 50) showed reduced disability in the treatment group, with statistically significant differences in post-treatment FIM motor scores for the two groups (p<0.001). There was a clinical and statistically significant improvement in FIM (motor) total scores (p<0.001), and the FIM motor domains of: transfer (p<0.001), locomotion (p<0.001), self-care (p<0.001) and the FIM cognitive subscale (p<0.016). In the treated group, 70.8% improved compared with 13% of controls. Significantly more patients in the control group deteriorated over the study period (58.7% vs 16.7%; p<0.001). There were no differences between the control and treatment group scores on the MSIS-physical (p = 0.18), MSIS-psychological (p = 0.45) or GHQ subscales.
                An individualised rehabilitation programme reduces disability in persons with MS compared with no intervention. The impact of rehabilitation on QoL needs further evaluation. More information on the effectiveness of the various components of the multidisciplinary rehabilitation programmes are now needed. Australian clinical trials registry: Trials registration number: ACTRNO12605000676617. We evaluated a rehabilitation programme for executive deficits in multiple sclerosis patients by comparing outcome scores of a cognitive intervention group (CIG; n = 11) with those of a placebo group (n = 14) and an untreated group (n = 15). Executive functioning and verbal learning improved significantly more in the CIG. The treatment effect on verbal learning was still present at 1-year follow-up. Baseline brain atrophy, quantified by the brain parenchymal fraction, was associated with treatment effects for one aspect of executive functioning. Consequently, cognitive intervention may be beneficial and baseline brain atrophy has some predictive value in determining treatment outcome for executive functioning. Specialist nurses are being promoted as a means of improving the health care provided to people with multiple sclerosis (MS).
                To identify the impact of a programme of MS specialist nurses on MS health care provision and on the health and well-being of people with MS.
                A quasi-experimental design comparing an intervention group in which new MS nurse posts were installed with a control group that had no MS nurse posts.
                Six neurological services in four English regions.
                Seven hundred and fifty-three of the 1510 people invited to participate returned completed questionnaires at baseline. Follow-up of participants was 82% with 616 patients participating in the main outcome analysis.
                Data were collected prospectively before the appointment of the MS nurses and then at 12 and 24 months. Data were collected via a postal questionnaire comprising questions related to care processes (information provision and care quality) and health outcome measures, hospital admissions, MS complications, health-related quality of life (SF36) and disease impact (MS Impact Scale-29). Analysis repeated measures in CAT MOD for process variables and ANCOVA to longest follow-up for outcome measures.
                Information provision was higher in the intervention group (68% (n=153) compared to 53% (n=98) at 24 months) but no significant improvement was observed in information provision through time compared to the control group. There was an increase in the availability of a contact person in the intervention group, at 24 months 83% (n=42) had a contact person compared to 44% in the control (p=0.01). The only significant finding in relation to MS complications was a reduction of 17% in the incidence of pressure ulcers in the intervention sites compared to a 3% reduction in the control (p<0.001). In relation to the disease and health-related quality of life measures, the intervention group showed a small but significant (p<0.05) worsening in the physical and symptom scales of the SF36 compared to the control (mean differences: physical function -2.81, CI -5.45 to -0.1; bodily pain -4.09, CI -7.2 to -0.9; general health -5.35, CI -8.1 to -2.5; and energy and vitality -2.82, CI -5.5 to -0.1). No differences were observed in relation to disease impact or psychosocial well-being, although a relative benefit in mental health (with a 7.8 point advantage on the SF36 mental health scale, p=0.04) was observed in some of the intervention sites for people with relapsing/remitting MS.
                The specialist nurse programme was found to impact positively on the provision of MS-related health care. However, there was very limited evidence that the programme led to any improvements in disease-related problems, impact or health-related quality of life, These findings were in part explained by the inherent difficulties of measuring effects in evaluations of complex phenomena such as a nursing role. The deterioration observed in the intervention group on the physical outcome measures was explained by a selection bias in which people with worsening health were more likely to seek contact with a specialist nurse. It is contended that future research in this area may be better directed toward identifying specific interventions that nurses and other health professionals might employ in addressing the many problems confronting people with MS. Interferon (IFN) beta has repeatedly shown benefit in multiple sclerosis (MS) in reducing the rate of relapse, the disease activity as shown with magnetic resonance imaging and, to some degree, the progression of disability; however, it is unknown how much the therapeutic response depends on the dose, the subgroup involved, and the disease stage. This multicentre, double blind, placebo controlled study explored the dose-response curve by examining the clinical benefit of low dose IFN beta-1a (Rebif), 22 micro g subcutaneously once weekly, in patients with secondary progressive MS.
                A total of 371 patients with clinically definite SPMS were randomised to receive either placebo or subcutaneous IFN beta-1a, 22 micro g once weekly, for 3 years. Clinical assessments were performed every 6 months. The primary outcome was time to sustained disability, as defined by time to first confirmed 1.0 point increase on the Expanded Disability Status Scale (EDSS). Secondary outcomes included a sensitive disability measure and relapse rate.
                Treatment had no beneficial effect on time to confirmed progression on either the EDSS (hazard ratio (HR) = 1.13; 95% confidence interval (CI) 0.82 to 1.57; p = 0.45 for 22 micro g v placebo) or the Regional Functional Status Scale (HR = 0.93; 95% CI 0.68 to 1.28; p = 0.67). Other disability measures were also not significantly affected by treatment. Annual relapse rate was 0.27 with placebo and 0.25 with IFN (rate ratio = 0.90; 95% CI 0.64 to 1.27; p = 0.55). The drug was well tolerated with no new safety concerns identified. No significant gender differences were noted.
                This patient population was less clinically active than SPMS populations studied in other trials. Treatment with low dose, IFN beta-1a (Rebif) once weekly did not show any benefit in this study for either disability or relapse outcomes, including a subgroup with preceding relapses. These results add a point at one extreme of the dose-response spectrum of IFN beta therapy in MS, indicating that relapses in this phase may need treatment with higher doses than in the initial phases.
We were unable to achieve all of the objectives specified for the review. This review shows that the overall effect of CFX (administered as intensive schedule) in the treatment of progressive MS does not support its use in clinical practice.