Measuring deterioration in international classification of functioning domains of people with multiple sclerosis who are ambulatory.

BACKGROUND AND PURPOSE: Measures to detect important effects related to physical therapy interventions must be able to detect an important change. The purpose of this study was to select the most responsive physical functioning measures for multiple sclerosis (MS) using the International Classification of Functioning, Disability and Health (ICF) as a framework. SUBJECTS: The participants were 120 people with MS who were ambulatory from a population-based sample. METHODS: Physical functioning was assessed by quantitative clinical measures of activities (n=5) and body functions (n=7) and by self-reported performance in self-care, mobility, and domestic life domains in the activities and participation component of the ICF at baseline and 2 years later. A participant's perception of change and a change in Expanded Disability Status Scale (EDSS) scores were used as external criteria in the analysis of the receiver operating characteristic curve and the minimally important change score. The minimal detectable change was calculated as distribution-based responsiveness. RESULTS: According to the external criteria, 51% of the participants showed deterioration as measured by their own perceptions compared with the 26% of the participants who showed deterioration as rated by the clinician. Regardless of the external criterion applied, the measures most responsive to deterioration were self-reported scores in self-care, mobility, and domestic life; distance walked and change in heart rate during a 6-minute walk test; 10-m walk test speeds, stride length, and cadence; repetitive squatting; and Box and Block Test scores. DISCUSSION AND CONCLUSION: The results show the relative responsiveness of different measures in the subsample who deteriorated and provide data that can facilitate the interpretation of score changes in people with MS who are ambulatory for future studies and in clinical practice.

Measures of physical functioning predict self-reported performance in self-care, mobility, and domestic life in ambulatory persons with multiple sclerosis.

OBJECTIVE: To determine the associations between clinically measured physical functioning variables and self-reported performance in mobility, self-care, and domestic life in ambulatory persons with multiple sclerosis (MS), using the International Classification of Functioning, Disability and Health (ICF) as a framework. DESIGN: Survey study. SETTING: Community setting in Finland. PARTICIPANTS: A population-based sample of 120 ambulatory persons with MS (30 men, 90 women) with mean age 45.0+/-10.8 years (range, 20-71 y), mean disease duration from symptom onset 12.3+/-8.8 years (range, 1-39 y), and mean Expanded Disability Status Scale 2.8+/-2.0 (range, 0-6.5). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary dependent variables were self-reported performance in self-care, mobility, and domestic life from the Functional Status Questionnaire. The physical functioning variables were drawn from the ICF activities (n=9) and body functions (n=14) categories. Age- and sex-adjusted odds ratios from multinomial logistic regression were estimated for the physical functioning variables associated with activities of daily living (ADL) performance. RESULTS: Overall, of this cohort 31% reported difficulties or dependence in self-care, 52% in mobility, and 68% in domestic life. The most significant predictors of perceived difficulties or dependence in ADL performance were: (1) lower scores in the Box and Block Test; (2) lower Berg Balance Scale scores; (3) greater velocity moment when standing with eyes open; (4) slower ten-meter walk test times and shorter stride length at normal speed; and (5) shorter distance in the six-minute walk test. CONCLUSIONS: Perceived difficulties and dependence were most prominent in domestic life. In particular, measures of activities predicted difficulties in ADL performance. Monitoring of physical functioning should be extended to those independent MS persons reporting difficulties in ADL performance.

Physical functioning in multiple sclerosis: a population-based study in central Finland.

OBJECTIVE: To describe multiple sclerosis and its impact on individuals' perceived problems in functioning, particularly in the domains of self-care, mobility and domestic life. DESIGN: A population-based study in a prevalence cohort of multiple sclerosis subjects in Central Finland region carried out in the year 2000. SUBJECTS: A total of 240 subjects with multiple sclerosis. METHODS: A postal questionnaire for assessing physical functioning was developed. RESULTS: Ninety percent of the study population completed the study. Subjects' average age was 48.2 years (range 20-76 years) and time since symptom onset was 15.8 years (range 0-56 years). Of the subjects, 82% were fully independent in self-care activities and 53% in domestic life, 50% were able to walk without any perceived problems and 38% had a permanent need for a walking aid. Fatigue was the most frequent complaint having an impact on subjects' daily life. Ninety-five subjects out of 240 (40%) were engaged in working life. CONCLUSION: These data give a clear indication of favourable functioning in mobility, self-care and domestic life. However, the fact remains that multiple sclerosis is a disabling and costly disease. These results provide information for use by local and national authorities in planning and co-ordinating rehabilitation interventions and social services.

Organisational downsizing as a predictor of disability pension: the 10-town prospective cohort study.

OBJECTIVE: To examine whether downsizing, the reduction of personnel in organisations, is a predictor of increased risk of disability retirement among employees who kept their jobs. DESIGN: Prospective cohort study. Based on reductions of personnel in participants' occupation and workplace, employees were grouped into exposure categories of no downsizing (less than 8% reduction), minor downsizing (reduction between 8% and 18%), and major downsizing (more than 18% reduction). They were followed up for a five year period after downsizing. SETTING: Four towns in Finland. PARTICIPANTS: 19 273 municipal employees, aged 21-54 years. MAIN OUTCOME MEASURES: All permanent full disability pensions granted because of medical reasons below 55 years of age between 1 January 1994 and 31 December 1998 from the national registers. RESULTS: In all, 223 employees were granted a permanent disability pension. The overall rate for disability pensions per 1000 employees was 7.7 after no downsizing, 13.1 after minor downsizing, and 14.9 after major downsizing. Cox proportional hazard models adjusted for age, sex, occupational status, type of employment contract, and town showed 1.81 (95% confidence intervals 1.22 to 2.70) times higher risk of disability retirement after major downsizing than after no downsizing. CONCLUSIONS: The immediate financial advantages of downsizing need to be considered in relation to increased occupational disability and the resulting extra costs to employers and society.

Reliability of physical functioning measures in ambulatory subjects with MS.

BACKGROUND AND PURPOSE: One of the primary reasons for measuring outcomes during rehabilitation is to determine the effect of physiotherapy. Repeated measurement situations are susceptible to several sources of error, including inconsistencies caused by the subject, the procedure, the instrument and the examiner. Therefore, the reliability of the measures needs to be examined. METHOD: The present study used a repeated-measures design. Two studies were undertaken to examine the test-retest and inter-rater reliability for physical functioning measures. The interval between the measurements was one week. The sample consisted of 19 ambulatory subjects with multiple sclerosis (MS) in the test-retest and nine subjects in the inter-rater reliability study. The measures were selected to assess different domains of the World Health Organization International Classification of Functioning, Disability and Health (WHO, 2001). Several parameters of the Box and Block Test (BBT), the Berg Balance Scale (BBS), the Kela Coordination test, the postural stability test, the timed 10-metre gait test, the six-minute walk test, the shoulder tug test, grip strength, maximal isometric force of the knee extensors, muscle endurance tests, the modified Ashworth Scale and passive straight leg raise test were examined in terms of reliability. RESULTS: The intra-class coefficient (ICC) values for test-retest reliability were >0.80 in 17 of 23 parameters, and correspondingly so in 20 out of 26 parameters for inter-rater reliability. Poor reliability (defined as ICC < or = 0. 60) was obtained only for the patient classification index (PCI) of the six-minute walk test in the test-retest reliability study. In general, the coefficient of variation was good. A moderate amount of variability was discovered for the Kela Coordination test, and for postural stability and muscle endurance tests. The data obtained from the modified Ashworth Scale and the shoulder tug test were highly skewed and the percentage of agreement ranged between 63.9% and 93.4%. CONCLUSIONS: The study revealed acceptable test-retest and inter-rater reliability of these measures in ambulatory subjects with MS, with the exception of the Modified Ashworth Scale and the shoulder tug test.

HLA class II associated risk and protection against multiple sclerosis-a Finnish family study.

We analyzed the HLA class II haplotypes in 249 Finnish nuclear families and compared the frequencies of parental haplotypes transmitted or non-transmitted to multiple sclerosis (MS) patients. The most important predisposing haplotype was DRB1*15-DQB1*0602 (P<10(-6)) as expected and a weak predisposing effect of DRB1*04-DQB1*0302 was revealed after the elimination of DRB1*15-DQB1*0602. HLA-DRB1*01-DQB1*0501 and DRB1*13-DQB1*0603 were negatively associated with MS in transmission disequilibrium test, but only the DRB1*13-DQB1*0603 association remained significant (P=0.008) after the elimination of DRB1*15-DQB1*0602 haplotypes. Based on this study HLA class II haplotypes exhibit both predisposing and protective effects in MS.

Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis.

Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenesis of multiple sclerosis (MS), whereas sequence variations in the ICAM-1 gene could potentially be responsible for the genetic susceptibility to MS. We studied an association of MS with the 13,848A>G (K469E) polymorphism of the ICAM-1 gene in Finnish and Spanish cases and controls and affected families. An increased risk for the AA (Lys(469)/Lys(469)) genotype was found in both populations. The effect observed was found to be strongest among the HLA-DQB1*0602-positive subjects, which implies genetic heterogeneity of MS. Meta-analysis of all published datasets supports increased risk of MS for the ICAM-1 Lys(469) homozygotes (relative risk = 1.3, p = 0.002).

Multiple sclerosis in western Finland: evidence for a founder effect.

We have previously demonstrated that there is a high-risk focus for multiple sclerosis (MS) in the southern Ostrobothnian region of western Finland (population 376121 in 1993). Of the two southern Ostrobothnian health-care districts, Vaasa and Seinäjoki, the incidence and prevalence of MS were especially high in the latter. In recent genetic studies, we identified haplotypes of the myelin basic protein (MBP) gene in a group of MS patients originating from southern Ostrobothnia, suggesting a founder effect. This finding led us to explore the population history of the southern Ostrobothnia and correlate it with MS epidemiology. Southern Ostrobothnia can be divided into three distinct regions with respect to its historical settlement: Vaasa, Seinäjoki-south, and Seinäjoki-north. Vaasa, the coastal region was settled by Swedes, who immigrated during the 13th century. In Vaasa, the prevalence of clinically definite MS (CDMS) in 1993 was 107/10(5) (95% CI 90-124). Seinäjoki-south was populated from the 13th century onwards from southwestern Finland, a region which has been recognised as a high-risk focus of MS. In Seinäjoki-south, the prevalence of CDMS in 1993 was 219/10(5) (95% CI 190-247). Seinäjoki-north was inhabited rather late starting in the 16th century from eastern Finland. In Seinäjoki-north the prevalence of CDMS in 1993 was 136/10(5) (95% CI 108-164). The historical settlement pattern of the southern Ostrobothnia indicates that its population is quite heterogeneous. Seinäjoki-south has a very high prevalence of MS, significantly higher than its two neighbouring regions. The distinctive settlement history of Seinäjoki-south, the historical link with the other southwestern high-risk foci and molecular genetic evidence, suggest that a founder effect plays an important role in the high-risk of MS in western Finland.

Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.

Genome-wide linkage analyses performed in a Finnish study sample have identified four potential predisposing loci for multiple sclerosis (MS). Here we made an effort to restrict the wide linkage region on chromosome 17 with a dense set of 31 markers using multipoint linkage analyses and monitoring for shared marker alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish multiplex MS families originating from a regional subisolate that shows an exceptionally high prevalence of MS in order to minimize the genetic and environmental heterogeneity of the study sample. Thirty markers on the 23 cM initial interval gave positive pairwise LOD scores. We monitored for shared haplotypes among affected family members within a family, and identified an approximately 4 cM region flanked by the markers D17S1792 and ATA43A10 in 17 out of the 22 families (77.3%). The multipoint linkage analyses using Genehunter and SIMWALK 2.40 provided further evidence for the same 4 cM region, for example a maximal multipoint NPL score of 5.98 (P<0.0002). We observed nominal evidence for association to MS, with one marker flanking the shared region, and this association was replicated in the additional set of families. Using the combined power of linkage, association and shared haplotype analyses, we were thus able to restrict the MS locus on chromosome 17q from 23 cM to a 4 cM region covering a physical interval of approximately 2.5 Mb. Thus, this study describes the restriction of an MS locus outside the HLA region into a segment approachable by molecular tools.