End of life in multiple sclerosis: Disability, causes and place of death among cases diagnosed from 1981 to 2010 in Pirkanmaa hospital district in Western Finland.

BACKGROUND: Mortality risk and causes of death have been widely studied in MS. Surveys on conditions related to approaching death have not been conducted before in Finland. OBJECTIVE: Our aim was to sort out the possible needs for end of life (EOL) care in MS by examining causes, place of death and level of hospitalization by age and MS related disability before approaching death. MATERIALS: Data included information for MS patients diagnosed from 1981 to 2010 in a Finnish university hospital district. Information on place and causes of death and care prior to death was based on death certificates from Statistics Finland. Decedents initial disease course, disease modifying treatment (DMT) use and MS related disability status by using EDSS were achieved from hospital records. RESULTS: Data included 113 decedents. Level of disability showed EDSS 6.0 or higher in 54% of the patients. In relapsing onset MS (N 93, 80%) DMTs were used in 11%. Infections, respiratory or other, were the main immediate cause of death (51.3%, n 58) among cases with varying disability. Central or university hospital (42.5%) or community hospital ward (28.3%) were places of death in majority of cases and nursing home (13.3%), home (9.7%) or hospice (3.7%) less often. Place of death did not significantly differ between age-groups (Chi square p = 0.86). Mean age at death was 57 years (range 28-90, SD 13.86). Cardiovascular causes of death were reported mainly in age group 60 years or more and suicide in age group younger than 50 years. CONCLUSION: The level of hospitalization was high at end of life in all age-groups. High MS related disability and immobility among decedents likely relates to infections as the most common cause of death. Along with our and earlier surveys in this field, we showed that places of death and level of disability before death share similarities in both younger and older age groups highlighting the need of palliative care and end of life care plans in all MS patients with triggers of poor survival. The recently published consensus definition featuring palliative care guideline in MS is aimed at improving end of life care in MS. Our results point at need for future studies in order to assess the impact of palliative care treatment guidelines in MS.

Changes in multiple sclerosis epidemiology in Finland over five decades.

Finland is a high-risk region for multiple sclerosis (MS) with several epidemiological studies on the subject published since 1964, but these have not been comprehensively scrutinized. The objective of this study was to review previous studies of Finnish MS epidemiology, introduce new data on MS prevalence in western parts of Finland and do further analyses on data from previous studies. We performed a systematic search on articles regarding MS epidemiology in Finland in PubMed database, and all relevant articles were included in this review. MS prevalences in the western hospital districts of Vaasa, South Ostrobothnia and Pirkanmaa were calculated in 1980-2007 by using previously unpublished data obtained from a retrospective search from hospital administrative registries. To enhance comparability of the epidemiological figures, we calculated age-standardized prevalence of MS from the new data from western hospital districts and previous data from North Ostrobothnia, Southwest Finland and North Karelia. Marked regional differences in MS epidemiology were confirmed with concentration of the disease in the western and south-western parts of the country. The highest regional age-standardized MS prevalence of 288/100 000 was reported in South Ostrobothnia in 2007. A clear and stable increase in MS prevalence was observed through the decades, but the only marked increase in incidence happened in 1990s. Methodological differences hampered direct comparisons of different studies, highlighting the importance of common principles of reporting and standardizing the epidemiological figures. More comprehensive studies on MS epidemiology are still warranted to yield important information concerning the aetiology of the disease.

Multiple sclerosis prevalence in 2000 and 2010 in Western Finland.

OBJECTIVE: To study ten-year change in MS prevalence in the Province of Western Finland in Tampere University Hospital District located in 62.7°N, 23.7°E. METHODS: Age-standardized prevalence/105 by using direct standardization in European Standard Population (ESP2013) and crude prevalence/105 with 95% confidence interval (95% CI) were assessed among resident MS cases fulfilling Poser criteria by sex and disease course in 31.12.2000 and 31.12.2010. MS-related disability and disease-modifying treatment (DMT) use were estimated in 31.12.2010. RESULTS: Crude prevalence increased 49% from 129/105 (95% CI 121-137) in 2000 (N 1080) to 196/105 (187-203) in 2010 (N 1666). Age-standardized prevalence increased 45% from 133/105 (127-140) to 192/105 (184-200) and peaked in 40- to 49-year age-group. Age-standardized prevalence increased 58% among women from 176/105 (171-176) to 277/105 (270-284) and 31% among men from 91/105 (87-95) to 119/105 (115-124). Increase in RRMS was 61% from 111/105 (105-117) to 179/105 (171-186), and decrease in PPMS was 14% from 21/105 (19-24) to 18/105 (15-21).  In 2010 among the 52% RRMS cases on DMT, MS-related disability was mild in 50%. In total, cohort disability was mild in 46%, moderate to severe in 47%, and information was not available in 14%. CONCLUSION: A significant increase in prevalence was observed in Western Finland. Increase was higher among women and in relapsing-remitting onset MS. Disability showed age- and disease course-specific variation.

Interferon ß-1a subcutaneously 3 times/week clinical outcome in relapsing multiple sclerosis in Finland.

Prognostic factors and long-term treatment response of interferon ß-1a s.c tiw has not been studied in a real-life clinical cohort in Finland. The aim of the paper was to evaluate long-term treatment response, prognostic clinical factors and adherence among interferon ß-1a s.c tiw treated patients in Finland. A retrospective review of medical records was performed. Confirmed relapsing multiple sclerosis patients treated with interferon ß-1a s.c tiw 22µg or 44µg as their first treatment, from 1996 to 2010 in Western Finland, were included. Longitudinal generalized linear regression models were applied to assess risk of disability progression, using Expanded Disability Status Scale (EDSS), during the treatment period. Odd's ratios with 95% confidence intervals (95% CI) were calculated for risk factors: gender, age at diagnosis, treatment delay, dose, baseline EDSS and EDSS change in one year. Kaplan-Meier was applied to study median time to discontinuation. Mean duration of treatment in 293 cases was 2.9 years (min 0.04, max 13.5). EDSS increase vs. no increase in one-year carried a significant risk for long-term disability progression (1.20, 1.08-1.33). Older age, defined by a 10-year increase in age at diagnosis (1.43, 1.07-1.91) and one-year delay to treatment start showed an increased risk for disability progression (1.05, 0.99-1.11), but gender (0.66, 0.38-1.15) or initial dose (1.00, 0.45-2.25) showed no risk. Treatment was stopped in 37% due to disease activation at median of 1.7 years, and in 25% due to side effects at 9.3 months. Our results show that young age, a short delay to treatment start and slower disability progression were identified as factors for better outcome among cases with interferon ß-1a s.c tiw as their first disease modifying treatment.

Increasing Incidence in Relapsing-Remitting MS and High Rates among Young Women in Finland: A Thirty-Year Follow-Up.

Object. Gender and disease course specific incidences were studied in high- and medium-risk regions of MS in Finland. Methods. Age- and gender-specific incidences with 95% CIs were calculated in 10-year periods from 1981 to 2010. Poser diagnostic criteria were used and compared with the McDonald criteria from 2001 to 2010. Association between age and diagnostic delay over time was assessed by using the Kruskal-Wallis test. Results. 1419 (89%) RRMS and 198 (11%) PPMS cases were included. RRMS incidence increased with the female to male ratio (F/M) from 4,2/10(5) (F/M 1.9) to 9,7 (2.3), while that of PPMS decreased from 1,2 (1.6) to 0,7 (1.2). The use of McDonald criteria did not change the conclusion. The decreasing diagnostic delay and age at diagnosis in RRMS were associated within the 10-year periods and contrasted those in PPMS. Increasing female risk in RRMS was observed in the high-risk region. Conclusion. Increasing RRMS incidence and high female ratios shown in each age group indicate gender-specific influences acting already from childhood. A more precise definition of the risk factors and their action in MS is needed to provide a better understanding of underlying pathological processes and a rationale for the development of new preventive and treatment strategies.

Increased Female MS Incidence and Differences in Gender-Specific Risk in Medium- and High-Risk Regions in Finland from 1981-2010.

Background. MS incidence has increased among females, suggesting the presence of environmental effect. Object. Regional differences and temporal changes in gender-specific MS incidence were studied in Finland. Methods. Cases from Jan 1, 1981 to Dec 31, 2010 in Pirkanmaa, Seinäjoki and Vaasa districts were included. The standardized incidence rates (SIR), incidences per 10(5) person years with 95% confidence intervals (CI), and female-to-male ratios (F/M) were determined by district. Results. 1617 cases were included. Compared to Pirkanmaa, the MS risk was 1.9-fold (95% CI: 1.7-2.0) greater in Seinäjoki and 1.2-fold (95% CI: 1.1-1.4) in Vaasa, and the risk was high for both genders. The incidence trend stabilized in Seinäjoki and Vaasa, accompanied by an increase in the F/M ratio. A steady increase in Pirkanmaa was accompanied by a high F/M ratio. Conclusion. A high female preponderance accompanied a general increase in incidence since the 1990s, suggesting the influence of environmental factors. In high-risk districts, increased MS risk prevailed in both genders. High risk reflects both genetic and environmental effects. These effects may be shared with autoimmune diseases such as type 1 diabetes mellitus; the incidence of which follows MS in Finland. Population-based case-control studies are needed to identify these factor effects.