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  • 1. Alping, P.
    et al.
    Islam-Jakobsson, Protik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Novakova, L.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Björck, A.
    Axelsson, M.
    Malmeström, C.
    Fink, K.
    Frisell, T.
    Lycke, J.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Piehl, F.
    Superior efficacy and tolerability of rituximab as compared to fingolimod for MS patients switching from natalizumab due to positive JC virus serology2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 11, s. 555-555, artikel-id P1079Artikel i tidskrift (Övrigt vetenskapligt)
  • 2. Alping, P.
    et al.
    Svenningsson, A.
    Clinical Science Danderyd´s Hospital, Karolinska Institutet, Stockholm.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Burman, J.
    Dahle, C.
    Fink, K.
    Hillert, J.
    Lycke, J.
    Landtblom, A. -M
    Martin, C.
    Nilsson, P.
    Walentin, F.
    Olsson, T.
    Frisell, T.
    Piehl, F.
    Rituximab in multiple sclerosis: data from the swedish MS registry2016Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, s. 49-49Artikel i tidskrift (Refereegranskat)
  • 3. Alping, Peter
    et al.
    Frisell, Thomas
    Novakova, Lenka
    Islam-Jakobsson, Protik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Björck, Anna
    Axelsson, Markus
    Malmeström, Clas
    Fink, Katharina
    Lycke, Jan
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients2016Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 79, nr 6, s. 950-958Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Many JC virus antibody-positive relapsing-remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy.

    Methods: We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%).

    Results: Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02-0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10-0.59) and 0.07 (95% CI = 0.02-0.30), respectively. Furthermore, contrast-enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00-0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center).

    Interpretation: Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns.

  • 4. Alping, Peter
    et al.
    Piehl, Fredrik
    Langer-Gould, Annette
    Frisell, Thomas
    Burman, Joachim
    Fink, Katharina
    Fogdell-Hahn, Anna
    Gunnarsson, Martin
    Hillert, Jan
    Kockum, Ingrid
    Lycke, Jan
    Nilsson, Petra
    Olsson, Tomas
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Virtanen, Suvi
    Vrethem, Magnus
    Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations2019Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, nr 2, s. 230-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of >3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.

  • 5.
    Boremalm, Malin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Juto, A.
    Axelsson, M.
    Novakova, L.
    Frisell, T.
    Svenningsson, A.
    Lycke, J.
    Piehl, F.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis2019Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, nr 8, s. 1060-1067Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS.

    Methods: Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models.

    Results: A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ.

    Conclusions: In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.

  • 6.
    Granberg Sandlund, M.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diamant, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Quality of care in acute dizziness presentations2019Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, nr S1, s. 926-926Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background and aims: Dizziness is a common symptom at emergency departments. Studies have shown poor quality of care in acute dizziness presentations, including the overuse of computed tomography (CT) and failure to detect benign causes. This study aims to evaluate whether a management algorithm has improved the quality of care for dizzy patients at Umeå University Hospital, Sweden.

    Methods: This was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012–2014) and after (period 2, 2016-2017) the implementation of a management algorithm (see figure). Outcomes were changes in a set of pre-defined quality markers and health economic effects.

    Results: Total n=2126 and n=1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix-Hallpike testing increased, 20.8% vs. 37.7%, (p<0.01), as did BPPV diagnoses, 7.6% vs. 15.3%, (p<0.01). Hospitalization became less common, 61.5% vs. 47.6% (p<0.01). The proportion undergoing any neuroradiological investigation decreased, 44.8% vs. 36.3% (p<0.01) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.

    Conclusion: This study shows how the implementation of a management algorithm for dizzy patients can improve the quality of care and lower the expenses, without an increased number of missed stroke cases.

  • 7.
    Granberg Sandlund, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diamant, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Effectiveness of care in acute dizziness presentations2019Ingår i: European Archives of Oto-Rhino-Laryngology, ISSN 0937-4477, E-ISSN 1434-4726, Vol. 276, nr 9, s. 2389-2396Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: This study aims to evaluate whether a management algorithm has improved the effectiveness of care for dizzy patients at Umea University Hospital.

    Methods: This was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012-2014) and after (period 2, 2016-2017) the implementation of a management algorithm. Outcomes were changes in a set of pre-defined effectiveness markers and health economic effects.

    Results: Total n = 2126 and n = 1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix-Hallpike testing increased, 20.8% [95% confidence interval (CI) 18.8-23.0%] vs. 37.7% (95% CI 35.2-40.2%), as did BPPV diagnoses, 7.6% (95% CI 6.6-8.8%) vs. 15.3% (95% CI 13.6-17.3%). Hospitalization became less common, 61.5% (95% CI 59.4-63.6%) vs. 47.6% (95% CI 45.1-50.2%). The proportion undergoing any neuroradiological investigation decreased, 44.8% (95% CI 42.7-47.0%) vs. 36.3% (95% CI 33.8-38.7%) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.

    Conclusions: This study shows that the implementation of a management algorithm for dizzy patients was associated with improved effectiveness of care.

  • 8.
    Granqvist, Mathias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Boremalm, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Poorghobad, Amyar
    Svenningsson, Anders
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Frisell, Thomas
    Piehl, Fredrik
    Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis2018Ingår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 75, nr 3, s. 320-327Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking.

    OBJECTIVE To assess the effectiveness and drug discontinuation rates of rituximab among patients with newly diagnosed RRMS compared with injectable DMTs, dimethyl fumarate, fingolimod, or natalizumab.

    DESIGN, SETTING, AND PATIENTS This retrospective cohort study used prospectively collected data to examine specialized care of 2 Swedish county-based community samples of patients with RRMS. Patients with RRMS who received diagnoses from January 1, 2012, to October 31, 2015, who resided in Stockholm or Vasterbotten Counties were identified from a Swedish multiple sclerosis registry.

    MAIN OUTCOMES AND MEASURES All reasons for drug discontinuation of initial treatment choice (main outcome) and specific reasons for switching (secondary outcomes) were analyzed with multivariable Cox regression, including propensity scores.

    RESULTS Among 494 patients (median [interquartile range] age, 34.4 [27.4-43.4] years; 158 men [32.0%]), 215 received an injectable DMT (43.5%); 86 (17.4%), dimethyl fumarate; 17 (3.4%), fingolimod; 50 (10.1%), natalizumab; 120 (24.3%), rituximab; and 6 (1.2%), other DMT. Regional preferences were pronounced, with 42 of 52 (81%) and 78 of 442 (18%) receiving rituximab in Vasterbotten and Stockholm, respectively. The annual discontinuation rate for rituximab, injectable DMTs, dimethyl fumarate, fingolimod, and natalizumab were 0.03, 0.53, 0.32, 0.38, and 0.29, respectively. Continued disease activity was the main reason for discontinuation of injectable DMTs, dimethyl fumarate, and fingolimod; positive John Cunningham virus serology results were the main reason for discontinuation of natalizumab. Rate of clinical relapses and/or neuroradiologic disease activity were significantly lower for rituximab compared with injectable DMTs and dimethyl fumarate, with a tendency for lower relapse rates also compared with natalizumab and fingolimod. The annual discontinuation rate of initial treatment choice was significantly lower in Vasterbotten compared with Stockholm (0.09 and 0.37, respectively).

    CONCLUSIONS AND RELEVANCE Rituximab was superior to all other DMT in terms of drug discontinuation and displayed better clinical efficacy compared with injectable DMTs and dimethyl fumarate with borderline significance compared with natalizumab and fingolimod. The county where rituximab constituted the main initial treatment choice displayed better outcomes in most measured variables. Collectively, our findings suggest that rituximab performs better than other commonly used DMTs in patients with newly diagnosed RRMS.

  • 9. Hallberg, S.
    et al.
    Boremalm, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Evertsson, B.
    Lillvall, E.
    Johansson, F.
    Lycke, J.
    Piehl, F.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, A.
    Risk of hypogammaglobulinemia in long-term treatment with rituximab in multiple sclerosis2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, s. 20-20Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Islam-Jakobsson, P.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Alping, P.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bjorck, A.
    Fink, K.
    Frisell, T.
    Piehl, F.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rituximab in multiple sclerosis, a long term safety and efficacy study2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 574-574Artikel i tidskrift (Övrigt vetenskapligt)
  • 11.
    Johansson, Elias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Interaction should guide management decisions2018Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 39, nr 5, s. E57-E57Artikel i tidskrift (Övrigt vetenskapligt)
  • 12. Khalil, Michael
    et al.
    Salzer, Jonatan
    CSF neurofilament light: A universal risk biomarker in multiple sclerosis?2016Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, nr 11, s. 1068-1069Artikel i tidskrift (Refereegranskat)
  • 13.
    Leckstroem, Daniel
    et al.
    London, England.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Goldsmith, David
    London, England.
    The trials and tribulations of vitamin D: time for the ‘sunshine’ vitamin to come in out of the cold – or just more broken promises?2014Ingår i: Expert review of Endocrinology & Metabolism, ISSN 1744-6651, Vol. 9, nr 4, s. 327-344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We are presently faced with the competing notions of modern life being a ‘state of vitamin D depletion’, implying a widespread need to supplement with vitamin D, or, the opposite view, which is that the present evidence can only support at best selective targeted vitamin D intervention. This is important as there is evidence that over the last 40–50 years there were downwards global trends in serum 25(OH)D concentrations, while individual consumption of vitamin D as supplements rose. For this reason and many others, a large population-based interventional study, the VITAL trial, was designed to try to establish the health value of vitamin D supplementation. VITAL is a huge primary prevention trial looking at the effects of vitamin D repletion in preventing cancer and cardiovascular disease in a fundamentally healthy population. This may seem an unusual approach given that what we mostly know about vitamin D is that is has some effects on the skeleton. This review looks to explore current knowledge about vitamin D in health and disease, and at how this is now undergoing significant reappraisal and revision. We will carefully critique the VITAL study design to see if it will allow for the construction of the detailed portfolio of clinical evidence so urgently needed to allow us better to understand role of vitamin D supplementation in health and disease. 

  • 14.
    Ljunggren, Micaela
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Persson, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dizziness and the Acute Vestibular Syndrome at the Emergency Department: A Population-Based Descriptive Study2018Ingår i: European Neurology, ISSN 0014-3022, E-ISSN 1421-9913, Vol. 79, nr 1–2, s. 5-12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dizziness is a common occurrence witnessed at emergency departments (EDs). This study aims to describe the epidemiology and management of dizzy patients with and without an acute vestibular syndrome (AVS) in the ED at Umea University Hospital. Methods: A total of n = 2,126 ED dizziness visits during 3 years were identified. Data were obtained through retrospective review of medical records. Cases were stratified based on presentation, including AVS and neurological deficits. The outcomes analyzed included cerebrovascular causes of dizziness. A Poisson distribution was assumed when calculating incidence CIs. Results: Dizziness accounted for 2.1% of all ED visits, incidence 477/100,000 inhabitants (95% CI 457-498). Among dizzy patients, 19.2% had an AVS, incidence 92/100,000 inhabitants (95% CI 74-113). Top medical diagnostic groups were otovestibular (15.1%), cardiovascular (8.7%) and neurological diseases (7.7%), including stroke and transitory ischemic attack (4.8%). Cerebrovascular causes of dizziness were more common among those with an AVS (10.0%) vs. those without (3.6%), p < 0.01. Conclusion: The risk for cerebrovascular causes of dizziness, although low in an unselected cohort, increases with the presence of neurological signs and an AVS. These population-based data may be useful when planning and implementing dizziness and AVS management algorithms at EDs.

  • 15.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Environmental risk factors for multiple sclerosis2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It usually strikes during young adulthood, and 2.5 million individuals are estimated to have the disease worldwide. The causes of MS are not known, but several factors have been shown to be associated with the risk of the disease, including certain genes, vitamin D, smoking and Epstein- Barr virus infection. Little is known about how/if these factors interact.

    Methods Study I: The risk of MS by month of birth was investigated using MS cases from the Swedish MS registry and using general population controls. Studies II–V: We identified MS cases who had donated blood prior to disease onset, and MS cases whose mothers had donated blood during pregnancy, by cross-linking a database of MS cases, and a database of mothers of MS cases, to two local biobank cohorts. One of them consisted of blood samples collected during early pregnancy, and one with samples collected during health controls. Levels of 25(OH)D (25-hydroxyvitamin D), RBP (retinol binding protein, a surrogate marker for vitamin A), CRP (C- reactive protein), cotinine (a nicotine metabolite) and anti Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibodies were measured in cases and matched controls. The risk of MS by categories of these exposures was estimated in bi- and multivariable matched logistic regression models.

    Results Subjects born in spring had a higher risk of MS, but no influence of early gestational levels of the measured risk factors on the risk of MS in the offspring was observed. In prospective samples from MS cases and controls, 25(OH)D levels ≥75 nmol/l, intermediate RBP levels, and elevated CRP levels in young were associated with a decreased risk of MS. Elevated cotinine levels (suggestive of smoking) and high antibody reactivity against EBNA-1 were associated with an increased risk of MS. All factors but RBP were more clearly associated with MS in young subjects.

    Conclusion All factors analyzed in prospectively collected samples were associated with the risk of MS, and taken together, the data indicate that the key etiopathological events that lead to MS occur before the age of 20–30. Study II provides support for trials exploring the primary preventive potential of oral vitamin D supplementation.

  • 16.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The only certain measure of the effectiveness of multiple sclerosis therapy is cerebrospinal neurofilament level - YES2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 10, s. 1239-1240Artikel i tidskrift (Refereegranskat)
  • 17.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Biström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vitamin D and multiple sclerosis: where do we go from here?2014Ingår i: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 14, nr 1, s. 9-18Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    This article briefly introduces the basics of multiple sclerosis' (MS) clinical hallmarks and pathophysiology. Vitamin D is presented, including its metabolism and effects on the immune system. The epidemiological observations linking vitamin D to MS range from a half century old findings of latitude gradients and migrational risk patterns to modern, nested, case-control biobank studies. These observations show an association without doubt although causation has yet to be proven. Vitamin D as a treatment for MS is an emerging concept and both current and anticipated data will be covered. Lastly, we discuss future challenges, ideas on how to move from association to causation, and the prospect of primary prevention of this disabling disease.

  • 18.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Goldsmith, David
    Cardio-Renal Medicine, King's Health Partners, London, UK.
    Maternal vitamin D status during pregnancy and bone-mineral content in offspring2013Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 382, nr 9894, s. 766-767Artikel i tidskrift (Refereegranskat)
  • 19.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Nyström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Smoking as a risk factor for multiple sclerosis2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 8, s. 1022-1027Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.

    Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.

    Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.

    Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).

    Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

  • 20.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Nyström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vitamin A and systemic inflammation as protective factors in multiple sclerosis2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 8, s. 1046-1051Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS).

    Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation.

    Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders.

    Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95).

    Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology. 

  • 21.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Nyström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vitamin D as a protective factor in multiple sclerosis2012Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, nr 21, s. 2140-2145Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine the association between 25-hydroxyvitamin D (25[OH]D) levels and the risk of multiple sclerosis (MS) in blood samples collected prospectively and during gestation.

    Methods: In this nested case-control study, 2 population-based biobanks with 291,500 samples from164,000 persons collected since 1975 in the northern half of Sweden were used. We identified prospectively collected blood samples from MS cases (n = 192, controls matched 2:1) and gestational samples from pregnant mothers where the offspring had later developed MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an ELISA, and the risk of MS was analyzed using matched logistic regression.

    Results: Levels of 25(OH)D ≥75 (vs <75) nmol/L in prospectively collected blood samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.16- 0.98). No decrease in MS risk was found in the offspring exposed to gestational 25(OH)D levels ≥75 (vs <75) nmol/L (OR 1.8, 95%CI 0.53-5.8). The prevalence of 25(OH)D levels ≥75 nmol/L in female controls decreased gradually during 1976-2005 (p trend = 0.005).

    Conclusion: This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH) D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

  • 22.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Wickström, Ronny
    Naver, Hans
    Piehl, Fredrik
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rituximab in paediatric onset multiple sclerosis: a case series2016Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 263, nr 2, s. 322-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Paediatric onset multiple sclerosis (POMS) is characterized by high inflammatory activity. No disease modifying treatment has been approved for POMS. The objective of this report was to report the use of rituximab, a B cell depleting monoclonal anti-CD20-antibody, in POMS. This is a retrospective case series at four specialized MS centres in Sweden. Participants were identified through the Swedish MS-registry and our own patient stocks. Data were collected through medical charts review. We identified 14 POMS patients treated with i.v. rituximab 500-1000 mg every 6th to 12th months. Median age at disease onset was 14.7 years, median age at rituximab treatment initiation was 16.5 years, and median treatment duration was 23.6 months. No relapses were reported, and the EDSS scores remained stable or decreased in 13 of 14 cases during rituximab treatment. Beyond 6 months from initiating rituximab treatment, only one new lesion was detected on MRI. No serious AEs were reported. The drug survival was 86 %. Our data indicate that rituximab treatment is safe, effective and well tolerated in children with MS. Nine POMS cases treated with rituximab have previously been published. They had higher disease activity pre-rituximab, but similar safety and efficacy outcomes after treatment. An RCT of rituximab in POMS is warranted.

  • 23.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Myhr, Kjell-Morten
    Epstein-Barr virus is a necessary causative agent in the pathogenesis of multiple sclerosis: No2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 13, s. 1692-1693Artikel i tidskrift (Refereegranskat)
  • 24.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nyström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels2013Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 12, s. 1587-1591Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.

    Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.

    Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.

    Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.

    Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.

  • 25.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rajda, C.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vågberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vecsei, L.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Are we minimizing the patients' risk for headache?: a lumbar puncture practice questionnaire study among European neurologists2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 733-734Artikel i tidskrift (Övrigt vetenskapligt)
  • 26.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rajda, Cecilia
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vågberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vecsei, Laszlo
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    How to minimize the risk for headache?: a lumbar puncture practice questionnaire study2016Ingår i: IDEGGYOGYASZATI SZEMLE-CLINICAL NEUROSCIENCE, ISSN 0019-1442, Vol. 69, nr 11-12, s. 397-402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background - To lower the risk for post lumbar puncture (LP) headache the American Academy of Neurology (AAN) recommended using small bore atraumatic needles together with stylet reinsertion in a report from 2005. It is unclear whether these recommendations are followed or not. Objectives To investigate the diagnostic LP preferences with respect to the AAN guidelines among neurologists by use of a short online questionnaire, and to review previously published literature on the subject. Results - A total of 284 respondents who performed diagnostic LPs completed the questionnaire. Almost half (41%) answered that they always use atraumatic needles. The most common reason (73%) for not using atraumatic needles was that these were not available. Less than half of the respondents who performed LPs had knowledge about the MN guidelines for diagnostic LPs, and 48-76% agreed with the different recommendations therein. Five previously (1998-2015) published studies investigating LP practice among neurologists were identified. The reported frequency of atraumatic needle use (always/routinely) varied between 2 and 16%. Discussion - Atraumatic needle use was more common in this study compared with previous publications. There is still skepticism regarding some of the MN recommendations, and needle availability appears to be the most important factor preventing atraumatic needle use. To increase the use of atraumatic needles we may perform additional studies investigating their potential benefits, and arrange training sessions for neurologists to increase their awareness and level of comfort with the atraumatic LP technique.

  • 27.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stenlund, Hans
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The interaction between smoking and Epstein-Barr virus as multiple sclerosis risk factors may depend on age2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 6, s. 747-750Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The multiple sclerosis (MS) risk factors smoking and remote Epstein-Barr virus (EBV) infection have been suggested to interact statistically, but the results are conflicting. In a prospective study on 192 MS cases and 384 matched controls, we analysed levels of cotinine as a marker of smoke exposure, and Epstein-Barr Nuclear Antigen-1 antibody reactivity. We assessed interaction on the additive and multiplicative scales, and estimated the effects of the risk factors across strata of each other. The results suggest that a negative interaction may be present in samples drawn at a young age, and a positive interaction among older subjects.

  • 28.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Timing of cigarette smoking as a risk factor for multiple sclerosis2013Ingår i: Therapeutic advances in neurological disorders, ISSN 1756-2856, Vol. 6, nr 3, s. 205-205Artikel i tidskrift (Refereegranskat)
  • 29.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Neurofilament light as a prognostic marker in multiple sclerosis2010Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 16, nr 3, s. 287-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Relapsing-remitting multiple sclerosis has a variable prognosis and lacks a reliable laboratory prognostic marker. Our aim in this study was to investigate the association between neurofilament light levels in cerebrospinal fluid in early multiple sclerosis and disease severity at long-term follow-up. Neurofilament light levels in cerebrospinal fluid collected at diagnostic lumbar puncture were measured in 99 multiple sclerosis cases. Clinical data were obtained from 95 out of those at follow-up visits made 14 years (range 8-20 years) after disease onset. Significant correlations between neurofilament light levels and the multiple sclerosis severity score were found for all cases (r = 0.30, p = 0.005), for relapsing-remitting multiple sclerosis cases (r = 0.47, p < 0.001) and for cases with a recent relapse (r = 0.60, p < 0.001). In the multivariate logistic regression analysis, neurofilament light levels >386 ng/L (median value of cases with detectable levels) increased the risk for severe multiple sclerosis fivefold (odds ratio 5.2, 95% confidence interval 1.8-15). Kaplan-Meier analysis showed that conversion to secondary-progressive multiple sclerosis was more likely in cases with neurofilament light levels >386 ng/L than in those with neurofilament light levels <60 ng/L (p = 0.01) or 60-386 ng/L (p = 0.03). We conclude that elevated levels of neurofilament light in cerebrospinal fluid collected at diagnostic lumbar puncture were associated with unfavourable prognosis. These data suggest that the neurofilament light level could be used as a prognostic marker in early relapsing-remitting multiple sclerosis.

  • 30.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Season of birth and multiple sclerosis in Sweden2010Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 122, nr 1, s. 70-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study supports previous results suggesting an association between the risk of MS and the season of birth. Decreased exposure to sun in the winter leading to low vitamin D levels during pregnancy is a possible explanation that needs further research.

  • 31.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Rasmus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Neuroscience, Danderyd Hospital, Karolinska Institutet, Stockholm.
    Alping, Peter
    Novakova, Lenka
    Björck, Anna
    Fink, Katharina
    Islam-Jakobsson, Protik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malmeström, Clas
    Axelsson, Markus
    Vågberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Piehl, Fredrik
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm.
    Rituximab in multiple sclerosis: a retrospective observational study on safety and efficacy2016Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, nr 20, s. 2074-2081Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). Methods: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. Results: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS). At baseline, 26.2% had contrast-enhancing lesions (CELs). Patients were treated with 500 or 1,000 mg rituximab IV every 6-12 months, during a mean 21.8 (SD 14.3) months. During treatment, the annualized relapse rates were 0.044 (RRMS), 0.038 (SPMS), and 0.015 (PPMS), and 4.6% of patients displayed CELs. Median Expanded Disability Status Scale remained unchanged in RRMS (p = 0.42) and increased by 0.5 and 1.0 in SPMS and PPMS, respectively (p = 0.10 and 0.25). Infusion-related AEs occurred during 7.8% of infusions and most were mild. A total of 89 AEs grades >= 2 (of which 76 infections) were recorded in 72 patients. No case of progressive multifocal leukoencephalopathy was detected. Conclusions: This is the largest cohort of patients with MS treated with rituximab reported so far. The safety, clinical, and MRI findings in this heterogeneous real-world cohort treated with different doses of rituximab were similar to those reported in previous randomized controlled trials on B-cell depletion therapy in MS. Classification of evidence: This study provides Class IV evidence that for patients with MS, rituximab is safe and effective.

  • 32.
    Salzer, Jonatan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wickstrom, R.
    Piehl, F.
    Lycke, J.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rituximab in paediatric MS2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 380-380Artikel i tidskrift (Övrigt vetenskapligt)
  • 33.
    Sandberg, L.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bistrom, M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vagberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundstrom, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vitamin D and axonal injury in multiple sclerosis2016Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, nr 8, s. 1027-1031Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Previous studies in patients with multiple sclerosis (MS) have shown an association between high serum 25-hydroxyvitamin D (25[OH]D) levels and decreased inflammatory activity. Objective: The purpose of this study was to examine the association between 25(OH)D levels and axonal injury in MS. Cerebrospinal fluid neurofilament light (CSF-NFL) was used as a marker for axonal injury. Methods: Patients were identified through clinical practice at the Department of Neurology in Umea University Hospital, Sweden. Blood draw, magnetic resonance imaging, scoring of disability and lumbar puncture were performed at inclusion in 153 patients, and also at median 12 months follow-up in 87 patients. For analyses of serum 25(OH)D levels and CSF-NFL, enzyme-linked immunosorbent assays were used. Results: There was an inverse association between serum 25(OH)D and CSF-NFL levels in categorical (dichotomized at 75 or 100 nmol/l) analyses. A dose-response effect for 25(OH)D levels on CSF-NFL levels (p for trend=0.034) was also present. Serum 25(OH)D levels above 100 nmol/l were associated with lower CSF-NFL levels independently of ongoing MS treatment. Conclusion: High 25(OH)D levels are associated with decreased axonal injury in MS.

  • 34.
    Sundstrom, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vitamin D and multiple sclerosis from epidemiology to prevention2015Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, nr Supplement 199, s. 56-61Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In the present review, we discuss observational and experimental data suggesting a protective effect from sun exposure and/or vitamin D in multiple sclerosis (MS). These data include geographic variations in MS occurrence, temporal trends, genetics, biobank, and questionnaire data. We look more closely at the differentiation between general effects from UV exposure, and those of vitamin D per se, including plausible mechanisms of action. Finally, primary prevention is touched upon, and we suggest actions to be taken while awaiting the results from ongoing randomized controlled trials with vitamin D in MS.

  • 35.
    Sundström, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vitamin D and multiple sclerosis: timing of sampling, treatment and prevention2013Ingår i: Biomarkers in Medicine, ISSN 1752-0363, Vol. 7, nr 2, s. 193-195Artikel i tidskrift (Övrigt vetenskapligt)
  • 36.
    Svenningsson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Lund University, Lund, Sweden.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vågberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Increasing prevalence of multiple sclerosis in Vasterbotten County of Sweden2015Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, nr 6, s. 389-394Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives To update the incidence and prevalence of multiple sclerosis (MS) in Vasterbotten County, Sweden, and to compare this to previous investigations in the same area. Background Northern Sweden is a high-risk area for developing MS. Vasterbotten County has previously been surveyed in detail regarding the occurrence of MS. In several countries, increases in MS prevalence and incidence as well as a change in the sex ratio have been reported. Materials and methods Multiple sources were used to identify MS cases in Vasterbotten that either had their onset of the disease from 1998 to 2010 and/or lived in Vasterbotten, the two dates chosen for prevalence calculation: the 31st of December 2005 and 2010. Results The mean yearly incidence of MS in Vasterbotten during the entire period 1998-2010 was 6.0/100,000. The female to male ratio was 2.1. The prevalence of MS in Vasterbotten was 188/100,000 on 31st of December 2005 and 215/100,000 on 31st of December 2010. The MS prevalence increased over time from 1990 to 2010. Conclusions The prevalence of MS in Vasterbotten County has increased between 1990 and 2010, while no statistically significant increase in incidence was seen.

  • 37.
    Svenningsson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vågberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study2014Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 83, nr 22, s. 2099-2100Artikel i tidskrift (Refereegranskat)
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