Publications from Institute of Health and Society

• Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål; Moen, Stine Marit & Celius, Elisabeth Gulowsen (2021). No significant differences in absenteeism or academic achievements in a Norwegian multiple sclerosis case control study. Multiple Sclerosis and Related Disorders.  ISSN 2211-0348. . doi: 10.1016/j.msard.2021.103141 Show summary

  Background: The duration and features of the multiple sclerosis (MS) prodrome are not well defined. We aimed to ascertain whether people with a future MS diagnosis have more days of absence and perform worse in upper secondary school than age, gender and county-matched controls. Methods: Using registry data from the southeast of Norway, we identified people with MS born ≥1978. Statistics Norway provided information on grades and days of absence in cases and matched controls. We looked at absence in the three years of upper secondary school and grades in the compulsory subjects Norwegian, English, mathematics and physical education. Results: We identified 107 cases with disease onset one year or more after graduation and 626 controls. There were no significant differences in absence or grades achieved in the population as a whole or in those with disease onset within four years of diagnosis, and no association between time to disease onset and days of absence or grades. Conclusion: There was no difference in days of absence or grades achieved in upper secondary school in the four years leading up to disease onset in cases compared to controls. A potential prodrome may not affect cognition enough to impact school achievements.

• Fossmark, Reidar; Olaisen, Maya; Martinsen, Tom Christian & Melberg, Hans Olav (2021). Factors associated with the persistence of oral 5-aminosalicylic acid monotherapy in ulcerative colitis: a nationwide Norwegian cohort study. Therapeutic Advances in Gastroenterology.  ISSN 1756-283X.  14, s 1- 10 . doi: 10.1177/17562848211021760 Show summary

  Background: Oral 5-aminosalicylic acid (5-ASA) is the mainstay treatment of ulcerative colitis (UC) and therapy with oral 5-ASA is associated with beneficial outcomes. We have examined factors associated with the persistence of oral 5-ASA treatment in a national cohort of UC patients. Methods: Patients with newly diagnosed UC from 2010 to 2014 using oral 5-ASA monotherapy were identified by combining data from the Norwegian Patient Registry and the Norwegian Prescription Database. The median follow-up time was 1029 days. Drug persistence was defined as duration of oral 5-ASA preparation as monotherapy. Non-persistence of a oral 5-ASA preparation as monotherapy was defined as stopping oral 5-ASA, initiation of any further anti-inflammatory treatment including a course of glucocorticoids and a change to another oral 5-ASA preparation. Drug persistence was analyzed using the Kaplan–Meier method and influence of covariates on drug persistence was analyzed with the Cox proportional hazard model. Results: A total of 3421 patients were identified. The overall median 5-ASA drug persistence was 179 days. In univariate analyses, persistence was associated with preparation type and high-dose treatment, while oral glucocorticoid use or hospitalization around the start of oral 5-ASA were associated with shorter 5-ASA persistence. In multivariate analyses, oral glucocorticoids [HR 1.67 (1.54–1.80), p < 0.005] and hospitalization around start of 5-ASA [HR 1.23 (1.14–1.34), p < 0.005] were associated with non-persistence, whereas high dose (⩾3 g/day) 5-ASA was associated with longer persistence [HR 0.68 (0.65–0.71), p < 0.005]. Conclusion: High-dose treatment with oral 5-ASA was associated with longer persistence of oral 5-ASA monotherapy, whereas the presence of factors indicating more severe disease around initiation of 5-ASA monotherapy was associated with a shorter persistence.

• Mesarić, Jasna; Šimić, Diana; Deilkås, Ellen Catharina Tveter; Hofoss, Dag & Bondevik, Gunnar Tschudi (2021). Variation in perception of safety culture in out-of-hours family medicine service in Croatia Razlike v dojemanju kulture varnosti pri dežurnih ambulantah družinske medicine na Hrvaškem. Slovenian Journal of Public Health.  ISSN 0351-0026.  60(3), s 1- 6 . doi: 10.2478/sjph-2021-0022
• Haugmark, Trond; Hagen, Kåre Birger; Provan, Sella Aarrestad; Sexton, Joseph & Zangi, Heidi Andersen (2021). Trajectories of change in symptom severity in patients with fibromyalgia: exploratory analyses of a randomised controlled trial. Rheumatology International.  ISSN 0172-8172.  41(4), s 691- 697 . doi: 10.1007/s00296-021-04801-x
• Sverdrup, Karen; Bergh, Sverre; Selbæk, Geir; Saltyte Benth, Jurate; Husebø, Bettina Elisabeth Franziska; Røen, Irene Mari; Thingstad, Pernille & Tangen, Gro Gujord (2021). Exploring life-space in the nursing home. An observational longitudinal study. BMC Geriatrics.  ISSN 1471-2318.  21(396) . doi: 10.1186/s12877-021-02345-0 Full text in Research Archive.
• Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Broch, Line; Brunborg, Cathrine; Berg-Hansen, Pål; Moen, Stine Marit; Kersten, Hege & Celius, Elisabeth Gulowsen (2021). Maternal education has significant influence on progression in multiple sclerosis. Multiple Sclerosis and Related Disorders.  ISSN 2211-0348. . doi: 10.1016/j.msard.2021.103052 Show summary

  Objective: The identification of potential risk factors for disease severity is of great importance in the treatment of multiple sclerosis. The influence of socioeconomic status on progression in multiple sclerosis (MS) is sparsely investigated. Our aim was to investigate how socioeconomic status in adolescence influences disease progression in later life. Methods: A total of 1598 patients with multiple sclerosis from a well-defined population in Norway were included. Detailed information on disease progression, measured by expanded disability status scale (EDSS) and multiple sclerosis severity score (MSSS), were combined with data on socioeconomic factors. We used residency and parental level of education at patients' age 16 and exposure to second-hand smoking as a measure of socioeconomic status in adolescence, adjusting for the same variables as well as use of disease modifying treatments at prevalence date 01.01.18. Results: High maternal level of education at patients' age 16 was significantly associated with less pronounced disease progression measured by MSSS (β-coefficient -0.58, p = 0.015), younger age and lower EDSS at disease onset, and shorter time from onset to diagnosis. No significant associations were found for paternal education level and MSSS. The use of any disease modifying treatment before prevalence date was significantly associated with disease progression (β-coefficient -0.49, p=0.004), while residence, current and second-hand smoking were not. Conclusion: This study on a population-based, real-world cohort shows that the parental level of education has a significant impact on a timely diagnosis of MS. In addition to disease modifying treatment, maternal level of education also had an impact on disease progression in later life.

• Aksnes, Mari; Aass, Hans Christian Dalsbotten; Tiiman, Ann; Edwin, Trine Holt; Terenius, Lars; Bogdanovic, Nenad; Vukojevic, Vladana & Knapskog, Anne Brita (2021). Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer's disease. Translational Neurodegeneration.  ISSN 2096-6466. . doi: 10.1186/s40035-021-00244-3 Full text in Research Archive. Show summary

  Background: The aggregation of amyloid β (Aβ) is central in the pathogenesis of Alzheimer's disease (AD). Recently it has been shown that specifically, larger, Thioflavin T-binding Aβ aggregates are associated with increased neuroinflammation and cytokine release. This study was aimed to quantify fibrillary amyloid aggregates, so-called nanoplaques, and investigate their relationship with cytokines in the cerebrospinal fluid (CSF). Methods: CSF was collected from 111 patients assessed for cognitive complaints at the Oslo University Hospital Memory Clinic. The patients were grouped based on their amyloid status. The CSF nanoplaque concentration was quantified with the Thioflavin T-fluorescence correlation spectroscopy (ThT-FCS) assay. The levels of nine cytokines (eotaxin-1, granulocyte stimulating factor, interleukin [IL]-6, IL-7, IL-8, monocyte chemoattractant protein-1, gamma-induced protein 10, macrophage inflammatory protein [MIP]-1α, and MIP-1β) were quantified with a magnetic bead-based multiplex assay and read on a Luminex IS 200 instrument. Results: There were 49 amyloid-negative and 62 amyloid-positive patients in the cohort; none of the cytokines differed significantly between the amyloid groups. The increased nanoplaque levels were associated with levels of MIP-1β below the lower limit of quantification, and with decreased levels of MIP-1α and IL-8. The associations remained significant when adjusted for age, sex, cognitive function, apolipoprotein ε4 status and CSF core biomarker levels. Conclusion: The cytokine levels were not associated with amyloid status in this cohort. The nanoplaque levels were negatively associated with MIP-1β, MIP-1α and IL-8, which is in line with recent findings suggesting that the upregulation of some cytokine markers has a protective role and is negatively associated with AD progression.

• Sundin, Ulf Gunnar; Sundlisæter, Nina Beate Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Nordberg, Lena Kristine Bugge; Hammer, Hilde Berner; Heijde, Desirée van der; Kvien, Tore Kristian; Haavardsholm, Espen A. & Lillegraven, Siri (2021). Value of MRI and ultrasound for prediction of therapeutic response and erosive progression in patients with early rheumatoid arthritis managed by an aggressive treat-To-Target strategy. RMD Open.  ISSN 2056-5933.  7:e001525(1), s 1- 11 . doi: 10.1136/rmdopen-2020-001525
• Strandenæs, Margit Gausdal; Lund, Anne; Engedal, Knut; Kirkevold, Øyvind; Selbæk, Geir; Saltyte Benth, Jurate & Rokstad, Anne Marie Mork (2021). Self-reported quality of life in people with dementia attending a day-care programme in Norway : A 24-month quasi-experimental study. Health and Social Care in the community.  ISSN 0966-0410. . doi: 10.1111/hsc.13455 Show summary

  The objectives of the study were (a) to compare self-reported Quality of Life (QoL) in a 24-month follow-up of people with dementia attending day care designed for people with dementia (day-care group, DC) with people with dementia who did not attend day care (control group, CG) and (b) to explore factors associated with QoL. A quasi-experimental design with a 24-month follow-up period was used. The DC group included 181 participants recruited from 53 day-care services. The CG included 76 participants recruited from 19 municipalities with no available day care designed for people with dementia. The sample covered the four health regions of Norway and inclusion period lasted from December 2013 to July 2015. The Quality of Life in Alzheimer's Disease (QoL-AD) scale was used as the outcome measure. The differences in QoL between groups and the associations between participant characteristics and QoL, such as depressive symptoms and functional dependency, were examined using a linear mixed model. In the multiple model, the overall trend in QoL did not differ significantly between the DC and CG. However, the DC group exhibited significantly higher self-reported QoL than the CG at all time points (p < 0.001 at T0, p = 0.018 at T12, and p = 0.006 at T24). Participants with shallow or no awareness who attended day care had significantly higher scores on QoL-AD than persons with full awareness (p = 0.017). More depressive symptoms (p < 0.001) and higher functional dependency (p < 0.001) were associated with lower self-reported QoL. The study revealed higher scores of self-reported QoL among people attending day care compared with those who did not attend, showing that day care might have positive impact on the lives of people with dementia.

• Camassa, Laura Maria Azzurra; Ervik, Torunn Kringlen; Zegeye, Fikirte Debebe; Mdala, Ibrahimu; Valen, Håkon; Ansteinsson, Vibeke Elise & Zienolddiny, Shanbeh (2021). Characterization and toxicity evaluation of air-borne particles released by grinding from twodental resin composites in vitro. Dental Materials.  ISSN 0109-5641. . doi: 10.1016/j.dental.2021.03.011 Show summary

  Objective The project aims to evaluate whether inhalation of particles released upon grinding of dental composites may pose a health hazard to dentists. The main objective of the study was to characterize the dust from polymer-based dental composites ground with different grain sized burs and investigate particle uptake and the potential cytotoxic effects in human bronchial cells. Methods Polymerized blocks of two dental composites, Filtek™ Z250 and Filtek™ Z500 from 3M™ ESPE, were ground with super coarse (black) and fine (red) burs inside a glass chamber. Ultrafine airborne dust concentration and particle size distribution was measured real-time during grinding with a scanning mobility particle sizer (SMPS). Filter-collected airborne particles were characterized with dynamic light scattering (DLS) and scanning electron microscopy (SEM). Human bronchial epithelial cells (HBEC-3KT) were exposed to the dusts in dose-effect experiments. Toxicity was measured with lactate dehydrogenase (LDH) assay and cell counting kit-8 (CCK8). Cellular uptake was observed with transmission electron microscopy (TEM). Results Airborne ultrafine particles showed that most particles were in the size range 15−35 nm (SMPS). SEM analysis proved that more than 80% of the particles have a minimum Feret diameter less than 1 μm. In solution (DLS), the particles have larger diameters and tend to agglomerate. Cell toxicity (LDH, CCK8) is shown after 48 h and 72 h exposure times and at the highest doses. TEM showed presence of the particles within the cell cytoplasm.

• Broch, Line; Simonsen, Cecilia Smith; Flemmen, Heidi Øyen; Berg-Hansen, Pål; Skardhamar, Åshild; Ormstad, Heidi & Celius, Elisabeth Gulowsen (2021). High prevalence of fatigue in contemporary patients with multiple sclerosis. Multiple Sclerosis Journal, Experimental, Translational and Clinical.  ISSN 2055-2173.  7(1) . doi: 10.1177/2055217321999826 Show summary

  Objective: The prevalence of multiple sclerosis (MS)-related fatigue may have changed due to new diagnostic criteria and new disease modifying drugs. We aimed to assess the prevalence of fatigue in a contemporary MS cohort, and to explore associations between fatigue and clinical and demographic factors. Methods: This is a cross-sectional study of the MS population in three Norwegian counties. Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC). We also assessed self-reported anxiety, depression and daytime sleepiness. Results: The response rate was 64% (1599/2512). The mean age of the participants was 52 ± 13 years, median EDSS was 2.5 (IQR 1.5-3.0) and median disease duration from onset was 16 years (IQR 8-25). We found a prevalence of fatigue of 81%. Women had a higher prevalence of fatigue than men (83% vs 78%, p = 0.02). The prevalence increased with age (p < 0.001) and with increasing disease severity (p < 0.001), but in multivariate analyses, only sex and disease severity remained independent determinants of fatigue. Anxiety, depression, and daytime sleepiness were more prevalent in patients with fatigue than in those without fatigue (all p-values < 0.001). Conclusion: The prevalence of fatigue is high in contemporary patients with MS. Fatigue is associated with female sex and level of disability, as well as with anxiety, depression and excessive daytime sleepiness.

• Hedenstierna, Louise; Bellocco, Rino; Ye, Weimin; Adami, Hans Olov; Åkerstedt, Torbjørn; Trolle Lagerros, Ylva & Hedström, Anna Karin (2021). Effects of alcohol consumption and smoking on risk for RA: Results from a Swedish prospective cohort study. RMD Open.  ISSN 2056-5933.  7(1), s 1- 7 . doi: 10.1136/rmdopen-2020-001379
• Aksnes, Mari; Tiiman, Ann; Edwin, Trine Holt; Terenius, Lars; Bogdanovic, Nenad; Vukojevic, Vladana & Knapskog, Anne Brita (2021). Comparison of cerebrospinal fluid amyloidogenic nanoplaques with core biomarkers of Alzheimer's disease. Frontiers in Aging Neuroscience.  ISSN 1663-4365.  12:608628, s 1- 11 . doi: 10.3389/fnagi.2020.608628 Full text in Research Archive.
• Edwin, Trine Holt; Strand, Bjørn Heine; Persson, Karin Ester Torun; Engedal, Knut; Selbæk, Geir & Knapskog, Anne Brita (2021). Neuropsychiatric symptoms and comorbidity: Associations with dementia progression rate in a memory clinic cohort. International Journal of Geriatric Psychiatry.  ISSN 0885-6230. . doi: 10.1002/gps.5500 Full text in Research Archive. Show summary

  Objectives Neuropsychiatric symptoms (NPS) are associated with dementia severity and progression rate. NPS clusters have different neurobiological underpinnings; therefore, their effect on dementia progression may differ. Further, little is known about whether individual comorbidities affect progression rate. We investigated the effect of NPS clusters and individual comorbidities on dementia progression. Methods A memory clinic cohort with all‐cause dementia (N = 442), was followed for up to three years from diagnosis. Previously, we found trajectory groups of dementia progression in this cohort: one with slow progression and two with rapid progression. In the present study, using principal component analysis, three symptom clusters of NPS were on the Neuropsychiatric Inventory Questionnaire (NPI‐Q): agitation, affective, and psychosis symptom clusters. Data regarding comorbidity were collected by linkage to the Norwegian patient registry. Multinomial logistic regression was applied to explore the association between NPS clusters and comorbidity with trajectory‐group membership. Results Adjusted for demographics, dementia aetiology, comorbidity, and cognition, we found that, at the time of dementia diagnosis, for every point within the psychosis symptom cluster of the NPI‐Q, the risk of rapid progression increased by 53%; for every point within the affective symptom cluster, the risk of rapid progression increased by 29%. A previous diagnosis of mental and behavioural disorders (excluding dementia) decreased the risk of rapid dementia progression by 65%. Conclusions Psychosis and affective symptom clusters at the time of diagnosis were associated with rapid progression of dementia. Previous diagnoses of mental and behavioural disorders (excluding dementia) were associated with slow progression.

• Gjøra, Linda; Strand, Bjørn Heine; Bergh, Sverre; Borza, Tom; Brækhus, Anne; Engedal, Knut Arne; Johannessen, Aud; Kvello-Alme, Marte; Krokstad, Steinar; Livingston, Gill; Matthews, Fiona E; Myrstad, Christian; Skjellegrind, Håvard; Thingstad, Pernille; Aakhus, Eivind; Aam, Stina & Selbæk, Geir (2021). Current and Future Prevalence Estimates of Mild Cognitive Impairment, Dementia, and Its Subtypes in a Population-Based Sample of People 70 Years and Older in Norway: The HUNT Study. Journal of Alzheimer's Disease.  ISSN 1387-2877. . doi: 10.3233/JAD-201275 Full text in Research Archive. Show summary

  Background: Having accurate, up-to-date information on the epidemiology of mild cognitive impairment (MCI) and dementia is imperative. Objective: To determine the prevalence of MCI and dementia in Norway using data from a large population-based study. Methods: All people 70 + years of age, n = 19,403, in the fourth wave of the Trøndelag Health Study (HUNT4) were invited to participate in the study HUNT4 70 + . Trained health personnel assessed participants using cognitive tests at a field station, at homes, or at their nursing home. Interviewers also completed a structured carer questionnaire in regard to participants suspected of having dementia. Clinical experts made diagnoses according to DSM-5 criteria. We calculated prevalence weighing the data to ensure population representativeness. Results: A total of 9,930 (51.2%) of the possible 19,403 people participated, and 9,663 of these had sufficient information for analysis. Standardized prevalence of dementia and MCI was 14.6% (95% confidence interval (CI) 13.9-15.4) and 35.3% (95% CI 34.3-36.4), respectively. Dementia was more prevalent in women and MCI more prevalent in men. The most prevalent dementia subtype was Alzheimer's disease (57%). By adding data collected from a study of persons < 70 years in the same region, we estimate that there are 101,118 persons with dementia in Norway in 2020, and this is projected to increase to 236,789 and 380,134 in 2050 and 2100, respectively. Conclusion: We found a higher prevalence of dementia and MCI than most previous studies. The present prevalence and future projections are vital for preparing for future challenges to the healthcare system and the entire society. Keywords: Alzheimer’s disease; dementia; epidemiology; population study; prevalence.

• Herber, Oliver Rudolf; Bradbury-Jones, Caroline; Böling, Susanna; Combes, Sarah; Hirt, Julian; Koop, Yvonne; Nyhagen, Ragnhild; Veldhuizen, Jessica D. & Taylor, Julie (2020). What feedback do reviewers give when reviewing qualitative manuscripts? A focused mapping review and synthesis. BMC Medical Research Methodology.  ISSN 1471-2288.  20(1) . doi: 10.1186/s12874-020-01005-y
• Borgen, Ida Maria Henriksen; Løvstad, Marianne; Røe, Cecilie; Forslund, Marit Vindal; Hauger, Solveig; Sigurdardottir, Solrun; Winter, Larraine & Kleffelgård, Ingerid (2020). Needs and treatment options in chronic traumatic brain injury: A feasibility trial of a community-based intervention. Cogent Medicine.  ISSN 2331-205X.  7(1) . doi: 10.1080/2331205X.2020.1731222
• Alves, Daniele Evelin; Nilsen, Wendy; Fure, Silje Christine Reistad; Enehaug, Heidi; Howe, Emilie Isager; Løvstad, Marianne; Fink, Louisa; Andelic, Nada & Spjelkavik, Øystein (2020). What characterizes work and workplaces that retain their employees following acquired brain injury? Systematic review. Annals of Occupational and Environmental Medicine (AOEM).  ISSN 2052-4374.  77, s 122- 130 . doi: http://dx.doi.org/10.1136/oemed-2019-106102

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• Andries, Aristomo; Van Walsem, Marleen Regina; Ørstavik, Kristin & Frich, Jan C (2021). Funksjonsevne og fysisk aktivitet hos personer med limb-girdle muskeldystrofi og Charcot-Marie-Tooth i Norge.
• Hagen, Terje P. & Hofmann, Bjørn (2020). Norway’s Response to the Coronavirus Pandemic.

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