Trends and characteristics of infection-related hospital admissions in multiple sclerosis patients in Southwest Finland in 2009–2018

BackgroundMultiple sclerosis (MS) patients are at increased risk for infections. The aim of this study was to investigate the trends in hospital admissions of patients with MS and to identify the factors predisposing to infection-related admissions.MethodsHospital admissions with MS as a primary or an auxiliary diagnosis in the hospital district of Southwest Finland in 2009–2018 were searched and MS patients with infection admissions compared with other MS patients in the hospital district. Data were derived from hospital registries, patient charts and the Finnish MS register. Group comparisons were performed using Pearson´s chi-squared test, Fisher´s exact test or Wilcoxon rank sum test. Overdispersion-adjusted Poisson regression was used to analyze the annual admission numbers and multivariable logistic regression to examine the predictors of infection-related admissions.Results1380 hospital admissions for 532 patients were identified. The annual number of admissions decreased by 8.9% annually (pConclusionHospital admissions, with or without an infection, have become more infrequent in MS patients of Southwest Finland over the decade from 2009 to 2018. Infection-related admissions were associated with lesser use of DMTs, older age, male gender and disability.</div

Finnish multiple sclerosis patients treated with cladribine tablets : a nationwide registry study

Background: Cladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement data from clinical trials.Methods: We investigated the use of cladribine tablets in Finland in a non-interventional cohort study, based on real-world data from the nationwide Finnish MS registry. All eligible patients who had initiated treatment with cladribine tablets in 2018-2020 were included. Descriptive analyses for outcomes were conducted using summary statistics. Time-dependent endpoints were analyzed using cumulated events analysis based on 1-Kaplan-Meier estimates and curves. Subgroups were analyzed separately according to the number of previous disease-modifying therapies (DMTs) and the most common last preceding therapies.Results: Data of 179 patients were analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of the 134 patients who were followed for at least 12 months, 112 patients (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) was 1.0 (standard deviation [SD] 0.89) at baseline, and 0.1 (SD 0.30) at follow-up. Patients with two or more previous DMTs had shorter time to first relapse (median 2.5 months, IQR 0.6-9.3) when compared to patients with 0-1 previous DMTs (median 11.4 months, IQR 8.7-13.1) (p=0.013). After excluding patients switching from fingolimod (n=33), a statistically significant difference in time to first relapse was no longer observed between the two groups (p=0.252). Adverse events (AEs) were reported in 30 patients (16.8%). The most frequent AE was headache (n=14, 7.8%). One patient (0.6%) died of cardiac arrest. Discontinuation of cladribine tablets was reported in nine patients (5.0%).Conclusion: The mean ARR observed in this cohort was similar to what has been reported in clinical trials. Approximately half of the patients had used two or more previous DMTs before cladribine tablets. These patients had a shorter time to first relapse when compared to patients with 0-1 previous DMTs, mostly driven by early relapses in patients switching from fingolimod.Peer reviewe

Multiple sclerosis in Finland 2018-Data from the national register

Objectives Finland is a high-risk multiple sclerosis (MS) region, but a national MS register has not existed until 2014. In this paper, we present the Finnish MS register variables and data collected by 31 December 2018. Materials and Methods Numbers and data counts of MS patients in the register (ICD-10 code G35) are presented. The disease types and proportion of patients receiving disease-modifying treatments (DMTs) were analysed in five hospital districts with most complete data sets. MS prevalence in Finland was estimated using administrative hospital discharge data as an additional resource. Results There were a total of 8722 MS patients in the Finnish MS register by 31 December 2018 (71.5% females). Mean age at MS diagnosis was 38.7 years and peak prevalence was at age 50-54 years. Disease course was relapsing remitting (RRMS) in 66.7%, secondary progressive (SPMS) in 13.5%, and primary progressive (PPMS) in 7.9% of the 5365 MS patients in the selected districts with most complete data. A total of 66.0% of RRMS patients, 19.6% of SPMS patients and 9.9% of PPMS patients were receiving DMTs. By combining MS register data with databases of those hospitals that had not joined the register, the nationwide prevalence estimate was between 10 and 11 thousand patients (corresponding to crude prevalence 180-200/100 000). Conclusions The Finnish MS register is currently used in 15/21 Finnish hospital districts. By register integration into the electronic patient files, the coverage of the register has increased to approximately 80% of the estimated Finnish MS population.Peer reviewe

How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients

Purpose Cardiac surgery and conventional extracorporeal circulation (CECC) impair the bioavailability of drugs administered by mouth. It is not known whether miniaturized ECC (MECC) or off-pump surgery (OPCAB) affect the bioavailability in similar manner. We evaluated the metoprolol bioavailability in patients undergoing CABG surgery with CECC, MECC, or having OPCAB. Methods Thirty patients, ten in each group, aged 44-79 years, scheduled for CABG surgery were administered 50 mg metoprolol by mouth on the preoperative day at 8-10 a.m. and 8 p.m., 2 h before surgery, and thereafter daily at 8 a.m. and 8 p.m. Blood samples were collected up to 12 h after the morning dose on the preoperative day and on first and third postoperative days. Metoprolol concentration in plasma was analyzed using liquid chromatography-mass spectrometry. Results The absorption of metoprolol was markedly reduced on the first postoperative day in all three groups, but recovered to the preoperative level on the third postoperative day. The geometric means (90% confidence interval) of AUC(0-12) on the first and third postoperative days versus the preoperative day were 44 (26-74)% and 109 (86-139)% in the CECC-group, 28 (16-50)% and 79 (59-105)% in the MECC-group, and 26 (12-56)% and 96 (77-119)% in the OPCAB-group, respectively. Two patients in the CECC-group and two in the MECC-group developed atrial fibrillation (AF). The bioavailability and the drug concentrations of metoprolol in patients developing AF did not differ from those who remained in sinus rhythm. Conclusion The bioavailability of metoprolol by mouth was markedly reduced in the early phase after CABG with no difference between the CECC-, MECC-, and OPCAB-groups.Peer reviewe

Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study

BACKROUNDCladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement data from clinical trials.METHODSWe investigated the use of cladribine tablets in Finland in a non-interventional cohort study, based on real-world data from the nationwide Finnish MS registry. All eligible patients who had initiated treatment with cladribine tablets in 2018-2020 were included. Descriptive analyses for outcomes were conducted using summary statistics. Time-dependent endpoints were analyzed using cumulated events analysis based on 1-Kaplan-Meier estimates and curves. Subgroups were analyzed separately according to the number of previous disease-modifying therapies (DMTs) and the most common last preceding therapies.RESULTSData of 179 patients were analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of the 134 patients who were followed for at least 12 months, 112 patients (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) was 1.0 (standard deviation [SD] 0.89) at baseline, and 0.1 (SD 0.30) at follow-up. Patients with two or more previous DMTs had shorter time to first relapse (median 2.5 months, IQR 0.6-9.3) when compared to patients with 0-1 previous DMTs (median 11.4 months, IQR 8.7-13.1) (p=0.013). After excluding patients switching from fingolimod (n=33), a statistically significant difference in time to first relapse was no longer observed between the two groups (p=0.252). Adverse events (AEs) were reported in 30 patients (16.8%). The most frequent AE was headache (n=14, 7.8%). One patient (0.6%) died of cardiac arrest. Discontinuation of cladribine tablets was reported in nine patients (5.0%).CONCLUSIONThe mean ARR observed in this cohort was similar to what has been reported in clinical trials. Approximately half of the patients had used two or more previous DMTs before cladribine tablets. These patients had a shorter time to first relapse when compared to patients with 0-1 previous DMTs, mostly driven by early relapses in patients switching from fingolimod.</p

Finnish multiple sclerosis patients treated with cladribine tablets : a nationwide registry study

Background: Cladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement data from clinical trials. Methods: We investigated the use of cladribine tablets in Finland in a non-interventional cohort study, based on real-world data from the nationwide Finnish MS registry. All eligible patients who had initiated treatment with cladribine tablets in 2018-2020 were included. Descriptive analyses for outcomes were conducted using summary statistics. Time-dependent endpoints were analyzed using cumulated events analysis based on 1-Kaplan–Meier estimates and curves. Subgroups were analyzed separately according to the number of previous disease-modifying therapies (DMTs) and the most common last preceding therapies. Results: Data of 179 patients were analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of the 134 patients who were followed for at least 12 months, 112 patients (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) was 1.0 (standard deviation [SD] 0.89) at baseline, and 0.1 (SD 0.30) at follow-up. Patients with two or more previous DMTs had shorter time to first relapse (median 2.5 months, IQR 0.6-9.3) when compared to patients with 0-1 previous DMTs (median 11.4 months, IQR 8.7-13.1) (p=0.013). After excluding patients switching from fingolimod (n=33), a statistically significant difference in time to first relapse was no longer observed between the two groups (p=0.252). Adverse events (AEs) were reported in 30 patients (16.8%). The most frequent AE was headache (n=14, 7.8%). One patient (0.6%) died of cardiac arrest. Discontinuation of cladribine tablets was reported in nine patients (5.0%). Conclusion: The mean ARR observed in this cohort was similar to what has been reported in clinical trials. Approximately half of the patients had used two or more previous DMTs before cladribine tablets. These patients had a shorter time to first relapse when compared to patients with 0-1 previous DMTs, mostly driven by early relapses in patients switching from fingolimod.publishedVersionPeer reviewe

Thalamic Atrophy Predicts 5-Year Disability Progression in Multiple Sclerosis

Purpose:Thalamus is among the first brain regions to become atrophic in multiple sclerosis (MS). We studied whether thalamic atrophy predicts disability progression at 5 years in a cohort of Finnish MS patients. Methods:Global and regional brain volumes were measured from 24 newly diagnosed relapsing MS (RMS) patients 6 months after initiation of therapy and from 36 secondary progressive MS (SPMS) patients. The patients were divided into groups based on baseline whole brain parenchymal (BP) and thalamic atrophy. Standard scores (zscores) were computed by comparing individual brain volumes with healthy controls. Azscore cutoff of -1.96 was applied to separate atrophic from normal brain volumes. The Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging (MRI) findings, and relapses were assessed at baseline and at 2 years and EDSS progression at 5 years. Results:Baseline thalamus volume predicted disability in 5 years in a logistic regression model (p= 0.031). At 5 years, EDSS was same or better in 12 of 18 patients with no brain atrophy at baseline but only in 5 of 18 patients with isolated thalamic atrophy [odds ratio (OR) (95% CI) = 5.2 (1.25, 21.57)]. The patients with isolated thalamic atrophy had more escalations of disease-modifying therapies during follow-up. Conclusion:Patients with thalamic atrophy at baseline were at a higher risk for 5-year EDSS increase than patients with no identified brain atrophy. Brain volume measurement at a single time point could help predict disability progression in MS and complement clinical and routine MRI evaluation in therapeutic decision-making.</div

Thalamic Atrophy Without Whole Brain Atrophy Is Associated With Absence of 2-Year NEDA in Multiple Sclerosis

Purpose: To study which brain volume measures best differentiate early relapsing MS (RMS) and secondary progressive MS (SPMS) patients and correlate with disability and cognition. To test whether isolated thalamic atrophy at study baseline correlates with NEDA (no evidence of disease activity) at 2 years.Methods: Total and regional brain volumes were measured from 24 newly diagnosed RMS patients 6 months after initiation of therapy and 2 years thereafter, and in 36 SPMS patients. Volumes were measured by SIENAX and cNeuro. The patients were divided into subgroups based on whole brain parenchyma (BP) and thalamic atrophy at baseline. Standard scores (z-scores) were computed by comparing individual brain volumes against healthy controls. A z-score cut-off of −1.96 was applied to separate atrophic from normal brain volumes. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed at baseline and at 2 years. Differences in achieving NEDA-3, NEDA-4, EDSS progression, and SDMT change were analyzed between patients with no thalamic or BP atrophy and in patients with isolated thalamic atrophy at baseline.Results: At baseline, 7 SPMS and 12 RMS patients had no brain atrophy, 8 SPMS and 10 RMS patients had isolated thalamic atrophy and 2 RMS and 20 SPMS patients had both BP and thalamic atrophy. NEDA-3 was reached in 11/19 patients with no brain atrophy but only in 2/16 patients with isolated thalamic atrophy (p = 0.012). NEDA-4 was reached in 7/19 patients with no brain atrophy and in 1/16 of the patients with isolated thalamic atrophy (p = 0.047). At 2 years, EDSS was same or better in 16/19 patients with no brain atrophy but only in 5/17 patients with isolated thalamic atrophy (p = 0.002). There was no significant difference in the EDSS, relapses or SDMT between patients with isolated thalamic atrophy and no atrophy at baseline.Conclusion: Patients with isolated thalamic atrophy were at a higher risk for not reaching 2-year NEDA-3 and for EDSS increase than patients with no identified brain atrophy. The groups were clinically indistinguishable. A single measurement of thalamic and whole brain atrophy could help identify patients needing most effective therapies from early on

Real-world treatment outcomes and safety of natalizumab in Finnish multiple sclerosis patients

Objectives: The primary objective was to evaluate long-term treatment persistence and safety of natalizumab in Finnish multiple sclerosis patients. The secondary objectives were to assess patient characteristics, use of natalizumab-related safety protocol, and treatment persistence in patients with different anti-John Cunningham virus antibody statuses (John Cunningham virus status). Materials & Methods: All adult multiple sclerosis patients in the Finnish multiple sclerosis register who started natalizumab between 1/2006 and 12/2018 were included in this study and followed retrospectively until treatment discontinuation or end of follow-up (12/2019). Results: In total, 850 patients were included. Median duration of natalizumab treatment was 7.8 years in John Cunningham virus negative (n = 229) and 2.1 years in John Cunningham virus positive patients (n = 115; p < 0.001). The most common cause for treatment discontinuation was John Cunningham virus positivity. After natalizumab discontinuation, patients who had a washout duration of less than 6 weeks had fewer relapses during the first 6 months (p = 0.012) and 12 months (p = 0.005) compared with patients who had a washout duration of over 6 weeks. During the median follow-up of 3.6 years, 76% of patients remained stable or improved on their Expanded Disability Status Scale. Conclusions: Treatment persistence was very high among John Cunningham virus negative patients. The study supports long-term effectiveness of natalizumab and a washout duration of less than 6 weeks after discontinuation.Peer reviewe

Aivojen MRI-pohjainen atrofia, haitta-aste sekä kognitio RRMS- ja SPMS-potilailla uudelleenpoimintamenetelmät apukeinona

Tässä tutkielmassa tarkastellaan ja verrataan MS-taudin kahden etenemismuodon potilaita, aaltomaisesti etenevän MS-taudin potilaita (RRMS-potilaat) sekä toissijaisesti etenevän MS-taudin potilaita (SPMS-potilaat), aivojen MRIpohjaisten muuttujien, kognitiivisen testin ja taudin haitta-asteen avulla. Aineiston muodostavat 24 RRMS-potilasta ja 36 SPMS-potilasta, joita on seurattu kahdessa eri aikapisteessä. Tarkoituksena on perinteisiä menetelmiä ja uudelleenpoimintamenetelmiä käyttäen ryhmien välinen vertailu aikapisteissä sekä muutosten osalta, ja eri aivoalueiden MRI-pohjaisen atrofian ja volyymin korrelaation tarkastelu suhteessa kognitiiviseen testiin sekä taudin haitta-asteeseen. Kaksi ensimmäistä kappaletta kattavat johdannon ja aineiston esittelyn. Tarkoituksena on tutustuttaa pintapuolisesti MS-tautiin ja sen etenemiseen, antaa aineistosta kattava kuva sekä testata ryhmien välisiä eroja yleisesti käytetyillä menetelmillä. Kolmannessa kappaleessa sovelletaan uudelleenpoimintamenetelmiä, saapasremmimenetelmää (bootstrap) sekä permutointia (permutation), harhan ja keskivirheen approksimointiin, ryhmien välisten erojen testaamiseen sekä korrelaatioon. Tässä tutkielmassa uudelleenpoimintamenetelmät tukivat hyvin perinteisesti käytettyjen menetelmien antamia tuloksia. Taudin haitta-asteen muutos ja normalisoidun otsalohkon volyymin suhteellinen muutos olivat SPMS-potilailla kahden aikapisteen välillä positiivisia, RRMS-potilaiden koko aivojen normalisoidun volyymin ja aivokuoren valkean aineen normalisoidun volyymin suhteellinen muutos olivat negatiivisia. Taudin haitta-asteella oli yksittäisissä aikapisteissä ilman ryhmittelyä monen eri aivoalueen ja kokonaisuuden volyymin kanssa negatiivinen merkitsevä korrelaatio, kognitiivisella testillä korrelaatio oli positiivista samojen muuttujien kanssa. Kognitiivisella testillä oli sen lisäksi SPMS-potilailla merkitsevä positiivinen korrelaatio molemmissa aikapisteissä normalisoidun pikkuaivojen valkean aineen volyymin kanssa