Consensus recommendations on the role of nurses in headache care: A European e-Delphi study.

BACKGROUND: Nurses work at headache centres throughout Europe, and their care for migraine patients is acknowledged. However, the specific roles and tasks of nursing vary, and a unified understanding is lacking, posing challenges to knowledge sharing and research. OBJECTIVES: Using an e-Delphi study method, the objective is to obtain healthcare professional headache experts' opinions on nursing-specific roles and tasks and combine this into consensus statements for nurse recommendations for migraine treatment. METHODS: A three-round questionnaire study was conducted with nurses and neurologists from 18 specialised headache centres in 10 countries. In round 1, statements were compiled from a systematic examination of existing literature and expert opinions. In rounds 2 and 3, the experts rated the importance of statements (from round 1) on a 5-point Likert scale. Statements were analysed using a content analysis method, and the consensus of pre-defined statements was evaluated with gradually increased predetermined criteria using descriptive statistics. RESULTS: Twenty-one experts, representing all 10 countries, participated. The predetermined consensus of ≥70% agreement was reached for 42 out of the initial 63 statements. These statements formed the final recommendations within two themes: "The nurses' roles and tasks in the clinical setting" and "The nurses' roles and tasks in educating patients and colleagues." The consensus level of statements was strong, with 40% receiving unanimous agreement (100%) and 97% achieving relatively high agreement (>80%). CONCLUSION: Nursing plays a vital role with diverse tasks in migraine care. This study offers practical recommendations and a framework for nurses, equipping them with a clinical tool to enhance care and promote a coordinated approach to migraine treatment.

Real-world effectiveness of fremanezumab for the preventive treatment of migraine: Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study.

BACKGROUND: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. METHODS: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1-12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1-12. Safety was assessed through adverse events reported. RESULTS: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1-12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. CONCLUSION: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries.Trial registration: encepp.eu: EUPAS35111.

Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families.

BACKGROUND: Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine. METHODS: We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project. RESULTS: Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02-0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08-0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14-0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26-0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31-0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk. CONCLUSIONS: The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.

Stroke and cardiovascular risk factors among working-aged Finnish migraineurs.

BACKGROUND: The aim of our study was to evaluate the risk for comorbid cardio- and cerebrovascular diseases in the working-aged migraine population of Finland. METHODS: A total of 1505 cases who reported diagnosed migraine and 3010 controls from a cohort of 11,596 cases in the Finnish Health and Social Support Study were included. The study material was linked with two registers. ICD diagnoses I63 for ischemic stroke (IS), I21 - I22 for acute myocardial infarction (AMI), and G43 for transient ischemic attack (TIA) among study participants were drawn from the national Finnish Care Register for Health Care at the follow-up in 2012. Reimbursed triptan prescriptions were drawn from the national Social Security Institution (SII) data. The self-reported vascular risk factors were hypertension, high cholesterol values, any diabetes, myocardial infarction, stroke, and TIA. Odds Ratios (OR) with 95% confidence (95% CI) intervals were assessed for diagnosed stroke, myocardial infarction, and TIA. RESULTS: Migraineurs were mostly female (82%) and ≥ 54 years old (62%). Triptans were reimbursed among 34.7% of migraineurs. A self-reported hypertension (21%), high serum cholesterol (38%), and any diabetes (7%) were more common among migraineurs vs controls (p < 0.05). There was no risk for AMI. The risk for TIA (OR 3.20, 95% CI 1.45-7.05) and IS (2.57, 95% CI 1.28-5.17) among migraineurs vs controls remained high after adjustment for self-reported hypertension, obesity, and smoking. The risk was higher among women in two groups ≥54 years (3.25, 95% CI 1.35-7.84 and 5.0, 95% CI 1.94-12.89, respectively). The average age for IS in migraine was 57.5 years and for TIA 58.2 years among women, and 52.8 years and 50.3 years among men, respectively. CONCLUSION: Cardiovascular risk should be screened in the aging migraine population, and hormonal and other migraine-related risk factors should be considered, especially among women. Efficacious attack treatment with triptans should be offered to migraine patients who do not show contraindications.

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.

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.

My Migraine Voice survey: disease impact on healthcare resource utilization, personal and working life in Finland.

BACKGROUND: A global My Migraine Voice survey was conducted in 31 countries among 11,266 adults who suffered from ≥4 monthly migraine days (MMD). The aim of this retrospective observational survey-based study was to analyse the country specific results in Finland in order to understand the impact of migraine based on disease severity. METHODS: The included participants (3%, n = 338/11,266) were stratified by mean MMDs into 4 ≤ MMD < 8 (n = 133), 8 ≤ MMD < 15 (n = 139) and MMD ≥ 15 (n = 66) subgroups. Comorbidities, migraine-related emotional burden and impact on daily living and work productivity and activity impairment (WPAI) were assessed. Subgroup analysis on healthcare resource utilization (HCRU) due to migraine was assessed by visits to healthcare practitioners (HCPs) during the past 6 months and by hospitalizations and emergency room (ER) visits during the past 12 months. The group difference was tested using the one-way ANOVA and for categorical variables using the Chi-squared test. The association between HCRU and MMD and number of comorbidities was assessed using negative binomial regression analysis. RESULTS: Mean age was 44 years, 93% were women and 67% (n = 227) were employed. Chronic migraine (CM, MMD ≥ 15) was reported in 19.5% of the respondents. The negative impact on daily functioning and emotional burden increased significantly by migraine frequency. Mean number of comorbidities was 2.4, and mean number of HCP visits during the previous 6 months was 5.9. Increase in migraine frequency and comorbidities was associated with higher HCRU. Eighty-eight percent of the respondents reported negative impact on working life and 52% experienced overall work productivity impairment. Over previous month, the mean number of missed working days for all respondents was 2.8 days of which 54% were paid sick leave days, and in CM up to 6.0 days and 30%, respectively. Both absenteeism and presenteeism were higher in the CM group. CONCLUSIONS: The emotional and functional burden was high, and the societal burden increased by frequency and severity of migraine, as shown by higher HCRU and reduced work productivity. There is a need to improve quality of care in migraine and improve migraine management related issues in both healthcare and society in Finland.

The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families.

Objective To study the position of hemiplegic migraine in the clinical spectrum of migraine with aura and to reveal the importance of CACNA1A, ATP1A2 and SCN1A in the development of hemiplegic migraine in Finnish migraine families. Methods The International Classification of Headache Disorders 3rd edition criteria were used to determine clinical characteristics and occurrence of hemiplegic migraine, based on detailed questionnaires, in a Finnish migraine family collection consisting of 9087 subjects. Involvement of CACNA1A, ATP1A2 and SCN1A was studied using whole exome sequencing data from 293 patients with hemiplegic migraine. Results Overall, hemiplegic migraine patients reported clinically more severe headache and aura episodes than non-hemiplegic migraine with aura patients. We identified two mutations, c.1816G>A (p.Ala606Thr) and c.1148G>A (p.Arg383His), in ATP1A2 and one mutation, c.1994C>T (p.Thr665Met) in CACNA1A. Conclusions The results highlight hemiplegic migraine as a clinically and genetically heterogeneous disease. Hemiplegic migraine patients do not form a clearly separate group with distinct symptoms, but rather have an extreme phenotype in the migraine with aura continuum. We have shown that mutations in CACNA1A, ATP1A2 and SCN1A are not the major cause of the disease in Finnish hemiplegic migraine patients, suggesting that there are additional genetic factors contributing to the phenotype.

Medical students' experience of emotions and success in neurological studies - What do they tell us?

BACKGROUND: There is a need to develop effective educational experience in neurology to improve the students' skills in diagnosing and managing patients with neurological symptoms or disease. The aim of this study was to investigate the medical students' attitudes and emotions towards neurology before and after the four week clinical course at two Finnish Universities in order to find elements to improve effective learning by decreasing the emotional stress in medical studies. METHODS: In this two-stage study, 58 medical students participated in an internet survey with open-ended questions after completing a clinical neurology course. In the content analysis of this survey 20 students (35%) were identified with negative anticipation towards neurology before undertaking the clinical neurology course. In the second phase of the study, the narrative analysis method was used to analyse the face-to-face interviews. Two of these interviews are described in this paper and represent cases who expressed negative emotions in both online survey and narrative interview. RESULTS: According to the content analysis, the principal emotions that were experienced at the beginning of the clinical neurology course were insecurity about personal performance (n = 19, 95%) anxiety (n = 9, 45%) and fear (n = 6, 30%). During the course the combined negative emotions (insecurity, anxiety, and fear) decreased in 80% of students (16/20 cases), remained unchanged in 15% (3/20) and could not be evaluated in 1 (5%) case. The main reasons for the observed negative anticipation were the complexity of neurology and challenges in the interpretation of clinical findings. Based on content analysis and narratives, elements that were evaluated as the most significant contributors in reducing this included small group teaching with real patients, teachers' expertise and the increase in self-confidence. CONCLUSION: Teaching with appropriate didactic methodology and feedback, and plenty of practical training can improve effective learning in neurology. We suggest that the pedagogic competence of the clinical teacher influences a student's motivation and proficiency and reduce stress in neurology-related learning tasks.

[Update on Current Care Guideline: Multiple sclerosis]. / Kaypa hoite-suosituksen paivitystiivistelma. MS-tauti.

Treatment for relapsing-remitting multiple sclerosis (RRMS) is initiated upon fulfillment of new McDonald 2010 criteria for RRMS. In addition, lumbar puncture is an essential diagnostic method. Interferon-ß, dimethyl fumarate, glatiramer acetate and teriflunomide are the first-line immunomodulating drugs (IMD) for RRMS. If the disease is active according to clinical or MRI evaluation during the first-line IMD treatment, alemtuzumab, fingolimod or natalizumab may be considered as second-line therapies. IMD treatment is discontinued upon the transition of RRMS to secondary progressive phase. Rehabilitation should be considered at every phase of the disease.

Cognitive impairment and its impact on employment: A qualitative interview-based study involving healthcare professionals and people living with multiple sclerosis.

BACKGROUND: Cognitive impairment can considerably impact the work life of people who have multiple sclerosis (MS). Cognitive symptoms are associated with an increased likelihood of unemployment, changes in employment and decreased working hours. This qualitative interview-based study aims to gather real-word experiences and perspectives from both people living with MS and healthcare professionals, to explore how cognitive symptoms are experienced in the workplace, how their impact is addressed, and what can be done to support people in managing and minimizing this impact on employment. METHODS: Semi-structured, one-to-one interviews were conducted with people living with MS who experience cognitive symptoms, and with healthcare professionals working in MS care. Participants were recruited from a healthcare market research agency based in the United States. The data obtained from the interviews were subsequently analysed using a Grounded Theory method, in order to identify the core themes that form the basis of this paper. RESULTS: A total of 20 participants (n = 10 people living with MS; n = 10 healthcare professionals) from the United States were interviewed. Overall, 9 themes were identified from the raw data, which were grouped into three core themes describing the perspectives and experiences reported by both people living with MS and healthcare professionals: (1) The implications of cognitive symptoms on work; (2) Challenges in addressing cognitive impairment and its impact on work in MS care; (3) Strategies and support for managing the impact of cognitive symptoms. CONCLUSION: The real-world insights of PwMS and HCPs gained from this qualitative study show that a multi-faceted approach to addressing cognitive impairment and its impact on the employment of PwMS is required. Workplace adjustments can range from self-implemented changes to changes put in place by employers to accommodate the various ways in which cognitive symptoms may impact a person's work. This study provides valuable information on how people living with MS can be affected by cognitive symptoms in the context of their employment; furthermore, that preparing early when possible and maintaining a proactive approach to managing their impacts on work are important for maintaining a good quality of life.

The association of menopausal hormone levels with progression-related biomarkers in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) progression coincides temporally with menopause. However, it remains unclear whether the changes in disease course are related to the changes in reproductive hormone concentrations. We assessed the association of menopausal hormonal levels with progression-related biomarkers of MS and evaluated the changes in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels during menopausal hormone therapy (MHT) in a prospective baseline-controlled design. METHODS: The baseline serum estradiol, follicle stimulating hormone, and luteinizing hormone levels were measured from menopausal women with MS (n = 16) and healthy controls (HC, n = 15). SNfL and sGFAP were measured by single-molecule array. The associations of hormone levels with sNfL and sGFAP, and with Expanded Disability Status Scale (EDSS) and lesion load and whole brain volumes (WBV) in MRI were analyzed with Spearman's rank correlation and age-adjusted linear regression model. Changes in sNfL and sGFAP during one-year treatment with estradiol hemihydrate combined with cyclic dydrogesterone were assessed with Wilcoxon Signed Ranks Test. RESULTS: In MS group, baseline estradiol had a positive correlation with WBV in MRI and an inverse correlation with lesion load, sNfL and sGFAP, but no correlation with EDSS. The associations of low estradiol with high sGFAP and low WBV were independent of age. During MHT, there was no significant change in sNfL and sGFAP levels in MS group while in HC, sGFAP slightly decreased at three months but returned to baseline at 12 months. CONCLUSION: Our preliminary findings suggest that low estradiol in menopausal women with MS has an age-independent association with more pronounced brain atrophy and higher sGFAP and thus advanced astrogliosis which could partially explain the more rapid progression of MS after menopause. One year of MHT did not alter the sGFAP or sNfL levels in women with MS.

Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene.

Genetic risk for multiple sclerosis (MS) is thought to involve both common and rare risk alleles. Recent GWAS and subsequent meta-analysis have established the critical role of the HLA locus and identified new common variants associated to MS. These variants have small odds ratios (ORs) and explain only a fraction of the genetic risk. To expose potentially rare, high-impact alleles, we conducted a GWAS of 68 distantly related cases and 136 controls from a high-risk internal isolate of Finland with increased prevalence and familial occurrence of MS. The top 27 loci with p < 10(-4) were tested in 711 cases and 1029 controls from Finland, and the top two findings were validated in 3859 cases and 9110 controls from more heterogeneous populations. SNP (rs744166) within the STAT3 gene was associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91). The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3 represents a shared risk locus for at least two autoimmune diseases. This study also demonstrates the potential of special isolated populations in search for variants contributing to complex traits.

[Woman, hormones and migraine]. / Nainen, hormonit ja migreeni.

Migraine is a problem of young working-age women in particular, and may influence the choice of the method of contraception. Other conditions causing headache should be taken into account in the differential diagnosis of migraine with an onset during pregnancy. Effective drugs are available for acute treatment, but in some attacks the effect of the drugs is insufficient. In women, these attacks are frequently associated with menstrual migraine. Recognition of prolonged and intense attacks as menstrual migraine, their anticipation and medication of attacks according to instructions are means to improve the treatment outcome.

A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon ß-1b in patients with multiple sclerosis.

OBJECTIVES: To study the safety and efficacy of vitamin D3 as an add on therapy to interferon ß-1b (IFNB) in patients with multiple sclerosis (MS). METHODS: 1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) ≥85 nmol/l or intact parathyroid hormone (PTH) ≤20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests. RESULTS: Median change in BOD was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105). Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110 (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (p<0.0001). Patients in the vitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate. CONCLUSION: Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS. TRIAL REGISTRATION NUMBER: EudraCT number 2007-001958-99 and ClinicalTrialsGov number NCT01339676.

Temporal variability of serum miR-191, miR-223, miR-128, and miR-24 in multiple sclerosis: A 4-year follow-up study.

BACKGROUND: Circulating microRNAs (miRNA) are suggested to be a promising biomarker for multiple sclerosis (MS). Previously, miR-128-3p, miR-24-3p, miR-191-5p and miR-223-3p have been reported to associate with MS pathology. However, their longitudinal changes and association with the disease activity have not been studied. OBJECTIVES: To evaluate the serum temporal variability of miR-128-3p, miR-191-5p, miR-24-3p, and miR-223-3p and their association with disability and disease activity in MS. METHODS: The expression of four miRNAs in serum was studied in 57 MS patients, 18 clinically isolated syndrome patients, and 32 healthy controls over the four-year follow-up. RESULTS: At the baseline, miR-191-5p was overexpressed in RRMS in comparison to controls, and its levels correlated positively with EDSS and progression index (PI) in RRMS. Increased levels of miR-128-3p were detected in PPMS in comparison to controls, and increased levels correlated with EDSS and PI in RRMS. The expression of miR-24-3p and miR-223-3p did not differ between the subtypes, but miR-223-3p correlated negatively with T1 lesions volumes in SPMS and PPMS. Over the four-years follow-up period, the expression of miR-128-3p and miR-24-3p was stable longitudinally, while temporal changes of miR-191-5p and miR-223-3p were observed in MS. Temporal changes in miR-191-5p were observed to be associated with an increase of EDSS or MRI activity, while the variability of miR-223-3p was associated with relapses. CONCLUSION: Temporal variability of miR-191-5p and miR-223-3p are associated with changes in disability accumulation and disease activity. While, miR-128-3p was stably expressed and associated with the PPMS subtype and correlated with disability accumulation.

Menopausal symptoms and hormone therapy in women with multiple sclerosis: A baseline-controlled study.

BACKGROUND: Depression, sleep disturbances, and cognitive difficulties impair the quality of life in people with multiple sclerosis (MS). Similar symptoms are also frequent during the menopausal transition. In clinical practice, it is important to consider the multifactorial causes of these overlapping symptoms and the potential benefits of menopausal hormone therapy (MHT). The objective of this study was to evaluate vasomotor symptoms (VMS), mood, sleep, and cognition of menopausal women with and without MS at baseline and during one year of MHT. METHODS: In this prospective baseline-controlled study, peri- and early postmenopausal participants with (n=14) and without (n=13) MS received MHT containing 1 or 2 mg of estradiol and cyclical 10 mg dydrogesterone for one year. VMS frequency, depressive symptoms (measured by Beck Depression Inventory), insomnia severity (Insomnia Severity Index), and cognitive performance (Paced Auditory Serial Addition Test; PASAT, Symbol Digit Modalities Test; SDMT) were evaluated at baseline and at 3 and 12 months of treatment. Differences in the outcome measures between groups at baseline were assessed using the Mann-Whitney U test. Changes during follow-up compared to baseline within groups were evaluated by Wilcoxon Signed Ranks Test. P < 0.05 was considered for statistical significance. MS activity was monitored by clinical assessment and brain MRI at baseline and at 12 months. RESULTS: Depressive symptoms were more common in MS group, while vasomotor and insomnia symptoms were equally common. During follow-up with MHT, VMS frequency decreased in both groups. Depressive symptoms decreased at 3 months (p = 0.031 with MS; p = 0.024 without MS) and the reduction was sustained at 12 months (p = 0.017; p = 0.042, respectively). Alleviation in insomnia symptoms was seen in participants without MS at 3 months (p = 0.029) and in those participants with MS suffering insomnia at baseline (p = 0.016 at 3 months; p = 0.047 at 12 months). Both groups improved their performance in PASAT, but no significant change was observed in SDMT. MS activity at baseline was mainly stable, and no increase in activity was detected during MHT. CONCLUSION: Improvements in vasomotor, depressive, and insomnia symptoms observed during one year of MHT are encouraging and suggest that larger placebo-controlled studies of MHT in women with MS are warranted. Cognitive implications were inconclusive because the findings in PASAT likely result from practice effect. MHT did not show any adverse effect on MS activity and increasing safety data will hopefully facilitate patient recruitment for future studies.

Prescription patterns in preventive and abortive migraine medication.

BACKGROUND: Migraine is considered a common but under-diagnosed and untreated condition. Treatment patterns have pointed at frequent over-the-counter medication use and low use of preventive therapies. Studies exploring migraine prescription practice among doctors are few. METHODS: A population-based study was carried out to examine the prescription practice in the use of acute and preventive migraine medications. The data covered 4864 working-age people reporting they have been diagnosed with migraine. Data on reimbursed prescription medicines from 1 January 1998 to 31 December 2006 were drawn from the registers of the Social Insurance Institute of Finland and compared with age- and sex-matched controls. RESULTS: Anti-inflammatory analgesics were prescribed for 71% of female and 62% of male migraine patients vs. 56% and 50% of controls. Triptans were prescribed for 21% of female and 10% of male patients. Combinations of analgesics and muscle relaxants were offered to 37% of female and 29% of male patients vs. 26% and 21% of controls, and antidepressants to 19% of women and 14% of men vs. 13% and 9% of controls. CONCLUSION: Although use of preventive medication among migraineurs was high, the prescription patterns in acute treatments showed that NSAIDS were used more often than triptans. Assimilation of national guidelines to treat migraine published in 2002 in Finland was not reflected in the prescription patterns up to 2006.

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.

Causes of death among patients with multiple sclerosis.

BACKGROUND: Several studies show a high mortality risk among patients with multiple sclerosis (MS). OBJECTIVES: In this study, mortality and underlying causes of death were analysed among patients with MS diagnosed between 1964-1993 in Finland (n = 1595). METHODS: Standardized mortality ratios (SMRs) were calculated for both genders. The follow-up was based on linkage to the national computerized Cause-of-Death Register of Statistics Finland. RESULTS: Altogether, 464 deaths were recorded by the end of 2006. The SMR as compared with the general population among females was 3.4 (95% confidence interval 3.0-3.9) and among males 2.2 (1.9-2.6). In total, 270 patients (58%) died from MS; only one of these deaths occurred during the first 2 years after the MS diagnosis. Mortality was also increased for other natural causes of death (n = 160) in patients followed for more than 10 years (SMR 1.4, 1.2-1.7), with a significant increase in deaths from influenza (29, 6.0-85), pneumonia (4.7, 2.5-8.0) and gastrointestinal causes (4.4, 2.3-7.7). The SMR for violent causes was 1.2 (0.7-1.9) and for alcohol-related deaths 0.2 (0.02-0.7). The SMR for suicides was 1.7 (0.9-2.7). CONCLUSIONS: The MS population has an increased disease mortality, while the increase in the risk of accidents and suicides is not significantly increased among patients with MS in Finland.