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BACKGROUND: The salutogenic approach in workplace health promotion emphasizes resources to gain and maintain good health and wellbeing. One of these resources could be calling, but its relation to the salutogenic approach is unknown. OBJECTIVE: To explore the associations between salutogenic measures of health and occupational wellbeing and calling among workers from the care and educational sectors. METHODS: A cross-sectional survey was conducted in Autumn 2020 among Finnish public and private sector care workers. A total of 7925 workers responded. Descriptive analyses and analysis of variance were used for the data analysis. RESULTS: Salutogenic measures of health and occupational wellbeing correlated strongly mutually, and both correlated moderately with calling. Workers aged over 55 years, workers acting in the education sector, workers with superior positions and temporary workers had the highest scores on health, occupational wellbeing and calling. When comparing occupational wellbeing dimensions by profession, managers had the highest scores and nurses the lowest. CONCLUSIONS: This study provides knowledge of promotive factors and health and occupational wellbeing resources for workplace health promotion in the care sector. Perceived calling in work can be considered a salutogenic resource for overall health and wellbeing; however, these connections should be further studied.

The salutogenic approach in workplace health promotion emphasizes resources to gain and maintain good health and wellbeing. One of these resources could be calling, but its relation to the salutogenic approach is unknown.To explore the associations between salutogenic measures of health and occupational wellbeing and calling among workers from the care and educational sectors.A cross-sectional survey was conducted in Autumn 2020 among Finnish public and private sector care workers. A total of 7925 workers responded. Descriptive analyses and analysis of variance were used for the data analysis.Salutogenic measures of health and occupational wellbeing correlated strongly mutually, and both correlated moderately with calling. Workers aged over 55 years, workers acting in the education sector, workers with superior positions and temporary workers had the highest scores on health, occupational wellbeing and calling. When comparing occupational wellbeing dimensions by profession, managers had the highest scores and nurses the lowest.This study provides knowledge of promotive factors and health and occupational wellbeing resources for workplace health promotion in the care sector. Perceived calling in work can be considered a salutogenic resource for overall health and wellbeing; however, these connections should be further studied.

Objective: Novel, highly effective disease-modifying therapies have revolutionized multiple sclerosis (MS) care. However, evidence from large comparative studies on important safety outcomes, such as cancer, is still lacking. Methods: In this nationwide register-based cohort study, we linked data from the Swedish MS register to the Swedish Cancer Register and other national health care and census registers. We included 4,187 first-ever initiations of rituximab, 1,620 of fingolimod, and 1,670 of natalizumab in 6,136 MS patients matched for age, sex, and location to 37,801 non-MS general population subjects. Primary outcome was time to first invasive cancer. Results: We identified 78 invasive cancers among treated patients: rituximab 33 (incidence rate [IR] per 10,000 person-years = 34.4, 95% confidence interval [CI] = 23.7–48.3), fingolimod 28 (IR = 44.0, 95% CI = 29.2–63.5), and natalizumab 17 (IR = 26.0, 95% CI = 15.1–41.6). The general population IR was 31.0 (95% CI = 27.8–34.4). Adjusting for baseline characteristics, we found no difference in risk of invasive cancer between rituximab, natalizumab, and the general population but a possibly higher risk with fingolimod compared to the general population (hazard ratio [HR] = 1.53, 95% CI = 0.98–2.38) and rituximab (HR = 1.68, 95% CI = 1.00–2.84). Interpretation: In this first large comparative study of 3 highly effective MS disease-modifying therapies, no increased risk of invasive cancer was seen with rituximab and natalizumab, compared to the general population. However, there was a borderline-significant increased risk with fingolimod, compared to both the general population and rituximab. It was not possible to attribute this increased risk to any specific type of cancer, and further studies are warranted to validate these findings.

Background Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE. Methods Seventy-two consecutive SLE out-patients and 26 healthy controls, all female, aged Results Plasma and CSF NfL concentrations correlated strongly (r = 0.72, p p = 0.003), non-NPSLE (0.83 (0.18), p = 0.005); SLICC B model: NPSLE (0.87 (0.14), p = 0.001), non-NPSLE (0.83 (0.18), p = 0.008); ACR model: NPSLE (0.86 (0.16), p p = 0.044)). Plasma and CSF NfL concentrations did not differ between NPSLE and non-NPSLE patients. Higher plasma NfL concentrations correlated with larger CSF volumes on MRI (r = 0.34, p = 0.005), and was associated with poorer cognitive performance in the domains of simple attention, psychomotor speed and verbal memory. SLICC/ACR-Damage Index ≥1 was independently associated with higher plasma NfL concentrations (β = 0.074, p = 0.038). Higher plasma creatinine concentrations, anti-dsDNA-positivity, low complement C3 levels, or a history of renal involvement were associated with higher plasma NfL concentrations (β = 0.003, p = 0.009; β = 0.072, p = 0.031; β = 0.077, p = 0.027; β = 0.069, p = 0.047, respectively). Conclusions Higher plasma NfL concentrations in NPSLE and non-NPSLE patients may indicate a higher degree of neuronal damage in SLE in general, corresponding to cognitive impairment and organ damage development. Furthermore, our results may indicate a higher degree of neuronal breakdown in patients with active SLE, also without overt clinical symptoms. NfL may serve as an indicator of neuronal damage in SLE in further studies.

Background: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.Methods: Using a repeated cross-sectional design, we included 2,165 persons with relapsing-remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.Results: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS >= 6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).Conclusion: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments. Funding Agencies|Patient-Centered Outcomes Research Institute (PCORI) Award [MS-1511-33196]; Swedish Research Council [2020-02700, TF 2016-01355]; Swedish Research Council for Health, Working Life, and Welfare [2020-0115]; NEURO Sweden

Additional file 1: Semi structured interview guide used in the focus groups.

Background Societal development and a competitive corporate climate have resulted in increased emphasis on performance management (PM) but also sustainability and health challenges in working life. Opportunities for employee well-being, development and performance are thus highly relevant for organisations and society. PM includes a manager-employee dialogue process and is identified as a complex challenge when combined with employee development and well-being. Managers have a key role in PM, and research in collaboration with practitioners in specific contexts is needed. An exploratory study, focusing on managers’ experience of dialogues between managers and employees in practice, was therefore conducted in collaboration with an inter-municipal corporation company in southern Sweden. Methods A qualitative study with an inductive design, supported by semi-structured focus group interviews, was chosen based on the exploratory character of the study. Thirty-five managers were approached in the company and 15, of varying age and managerial experience, agreed to participate. Staff Development Dialogues (SDD) were used in the company PM model to facilitate employee development, performance, and well-being. Data was analysed using conventional qualitative content analysis to obtain new insights without using pre-set classifications. Results The analysis resulted in three categories of SDD experiences: SDD in a business context; Managers in relation to SDD; and Employees in relation to SDD. The findings revealed varying SDD experiences as well as approaches, and analytical themes were considered in relation to the organisational context and the specific SDD content and process. The study showed the importance of SDD adaptation and a well-being perspective in the dialogues was related to relational aspects and the manager-employee approach to SDDs. Discussion The findings confirm the complexity and challenges of PM including development and well-being. Adaptation to specific departments as well as employees is important, and using the same PM strategy throughout an organisation can be questioned. The identified link between a relational approach and a well-being perspective indicates a missed opportunity for systematic workplace health promotion. Strengthening the well-being perspective can, thus, improve the quality of an SDD model, which in turn can facilitate the creation of sustainable workplaces and better fulfilment of employers’ health-related obligations for systematic work environment management.

The aim was to examine middle school-aged pupils’ participation in an action-oriented school health promotion project and investigate its effects on their health experience, learning and influence. A survey was sent eight times to middle school-aged pupils (n = 105). A descriptive analysis with group comparisons was followed by a regression analysis. Health differences were found between gender and age. Aspects of pupil influence and learning about health showed positive progression during the project. Satisfaction with school performance was most associated with health experience. Thus, health experience, gender, and age are factors to consider when planning similar health promotion projects in schools.

The aim was to explore the experiences of sexually abused individuals as dental patients. Purposively selected were 13 informants (11 women) aged 19-56. All had experienced sexual abuse as children or adults and memories of this abuse had been triggered and expressed during a dental appointment. They were encouraged to relate in their own words their experiences of the dental appointment. The interviews were recorded digitally, transcribed verbatim, and analysed according to Qualitative Content Analysis. The overall theme illustrating the latent content was The dental appointment - a volatile base requiring predictability and a secure working alliance. The first category covering the manifest content was The dental care provider "assumes responsibility," with two subcategories: (i) contradictory disclosure, and (ii) alliance formation - a levelling of power. The second category was The patient is "in focus," with two subcategories: (i) alertness to signs of discomfort, and (ii) attention to obvious but subtle expressions of needs. On an understanding that the patient has been sexually abused, an individually tailored, patient-centered approach to treatment is suggested. Dental care providers may also need to be aware of and reflect on their position of power, in relation to the patient and its possible chairside implications.

To investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms by examining functional connectivity changes correlating with results of cognitive testing. Structural MRI and resting state-fMRI (rs-fMRI) were performed in 61 female SLE patients (mean age: 36.8 years, range 18.2-52.0 years) and 20 healthy controls (HC) (mean age 36.2 years, range 23.3-52.2 years) in conjunction with clinical examination and cognitive testing. Alterations in core resting state networks, not found in our healthy controls sample, correlated with cognitive performance gauged by neuropsychological tests in non-neuropsychiatric SLE (nNP) as well as in neuropsychiatric SLE patients (NP). The observed pattern of increased functional connectivity in core resting state networks correlated with reduced cognitive performance on all cognitive domains tested and with a heavy focus on DM, CE, and DM-CE in the NP subgroup. Furthermore, we found that the observed alterations in memory and psychomotor speed correlated with disease duration. In SLE patients both with and without clinically overt neuropsychiatric manifestations, we found changes in the functional connectivity of core resting state networks essential to cognitive functions. These findings may represent a rewiring of functional architecture in response to neuronal damage and could indicate suboptimal compensatory mechanisms at play.

Background/Purpose Neuropsychiatric (NP) involvement and fatigue are both major problems in SLE. S100A8/A9 is a marker of inflammation, which responds to therapy in SLE patients. S100A8/A9 is expressed in the CNS. We investigated S100A8/A9 in relation to NPSLE and fatigue. Methods In this cross-sectional study we used ELISA (Bhulmann MRP8/14 ELISA kit, Switzerland) to measure the concentration of S100A8/A9 in serum in 72 SLE patients and 26 healthy controls and in cerebrospinal fluid (CSF) in 33 SLE patients. NP involvement was determined according to ACR case definitions for NPSLE. An MRI was performed in SLE patients and controls assessing white matter abnormalities and cerebral atrophy. Measurements of fatigue were performed using the Fatigue Severity Scale (FSS) and the Visual Analogue Scale (100 mm) (VAS). Statistical calculations were performed using non-parametric methods. Results In all, 72 female SLE patients (median age 38, range 18–52) and 26 female healthy controls (median age 40, range 23–52) were included in this study. Forty-four (61%) patients had NP involvement. NPSLE patients had higher serum S100A8/A9 concentrations (median 1.40 µg/ml) than the non-NPSLE patients (median 0.92 µg/ml; p=0.011) and the control group (median 0.79 µg/ml; p=0.004). Serum S100A8/A9 correlated with increased VAS fatigue in SLE patients (r=0.311; p=0.008), but not with FSS (r=0.184; p=0.124). Serum S100A8/A9 did not correlate with the extent of white matter lesions, atrophy of brain segments, or disease activity (SLEDAI-2K). S100A8/A9 was not detected in the CSF. Conclusions Higher serum S100A8/A9 concentrations in NPSLE patients and patients with fatigue may indicate that S100A8/A9 is involved in the pathogenesis of these manifestations, although further investigation is needed.

Workplace surveys are used in workplace health promotion as a basis for improvements at the workplace. But there is lack of psychometrically and qualitatively validated work-health related instruments with a salutogenic approach. The purpose of this study was, therefore, to evaluate the two instruments, the Salutogenic Health Indicator Scale and the Work Experience Measurement Scale, among staff of different professions in a healthcare setting. These instruments were evaluated with cognitive interviews conducted at a hospital in Sweden. The respondents were purposefully selected from various criteria such as profession, age, and sex (N = 14). The respondents read the items aloud and then spoke about how they experienced the items. A deductive (partly inductive) content analysis was done from Tourangeau’s four concepts of respondent actions: comprehension, retrieval, judgment, and response. Two main categories emerged: (1) interpreting and (2) responding, and an additional six subcategories: diffic...

Background: The impact of positive social relationships on the health of municipal employees in the elder care sector in Sweden needs further examination. OBJECTIVE: To explore the association between health and relationships among elderly care employees using a salutogenic perspective. METHOD: Survey of all employees (n = 997) in special housing, home care and Disabled Support and Services in a Swedish municipality. The questionnaire, which had a salutogenic perspective, included information on self-rated health from the previously validated SHIS (Salutogenic Health Indicator Scale), psychosocial work environment and experiences, social climate, and health-promoting workplace relationships. RESULTS: The response rate was 69%. Results of a multivariable linear regression model showed four significant predictors of health: general work experiences, colleague belongingness and positive relationships with managers and care recipients. In another model, colleague belongingness was significantly related to satisfaction with care recipients, work, length of employment as well as general work experiences and relationships with managers. CONCLUSION: Strengthening of positive work relationships, not only between workmates but also with managers and care recipients, seems to be an essential area for employee health promotion. Colleague belongingness may be deepened by development of a positive work climate, including satisfactory work experiences, positive manager relationships and a stable work force. (Less)

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Background: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited. Objective: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden. Methods: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF ( n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF ( n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016. Results: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37–0.58, p Conclusion: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

Relationships among colleagues, managers, and care recipients are mutually important, and need to be highlighted in workplace health promotion. The aim was to explore prerequisites for flourishing workplace relationships in a municipal healthcare setting for old people. As part of this process, we explored the staff’s suggestions on how work relationships could be improved. The study had a salutogenic and participatory approach, examining staff perceptions of what was required for flourishing relationships to be created, and their suggestions for the relationships to be more promotive. Four multi-stage focus groups, which met three times each, were conducted with staff (n = 26) in old age healthcare settings. A deductive analysis was performed, based on components of the flourishing concept: challenge, connectivity, autonomy, and competence. Informal and formal meetings at work were shown to build positively perceived relationships. The study describes meetings and relationships connected to the four components of flourishing. Suggestions for improving work relationships are also presented. This study contributes to workplace health promotion, and has a salutogenic and participatory focus on how to explore workplace relationships as a resource. The flourishing concept shows how workplace relationships can be explored as prerequisites for workplace health promotion., This article belongs to the Special Issue Sustainable Healthy Working Life for All Ages—Work Environment, Age Management and Employability

Incomplete unemployment data is a fundamental problem when evaluating labour market policies in several countries. Many unemployment spells end for unknown reasons; in the Swedish Public Employment Service’s register as many as 20 percent. This leads to an ambiguity regarding destination states (employment, unemployment, retired, etc.). According to complete combined administrative data, the employment rate among dropouts was close to 50 for the years 1992 to 2006, but from 2007 the employment rate has dropped to 40 or less. This article explores an imputation approach. We investigate imputation models estimated both on survey data from 2005/2006 and on complete combined administrative data from 2005/2006 and 2011/2012. The models are evaluated in terms of their ability to make correct predictions. The models have relatively high predictive power.

Autoimmune limbic encephalitis is part of CASPR 2 antibody-associated disease. A man with this rare disorder and a very high antibody titre had a unique history of laboratory exposure to the antigen. Together with earlier observations this case calls for caution in laboratory handling of nerve tissue.

Aims and objectives: To explore municipal healthcare employees' experiences of relationships with care recipients and colleagues. The specific research questions were when do the relationships enhance well-being, and what prerequisites are needed for such relationships to occur? Background: Employees in health and social care for older people often depict their work in negative terms, and they often take a high number of sick leaves. Despite the heavy workload, other employees express well-being at work and highlight social relationships as one reason for this. However, a greater understanding of how these relationships can act as resources for workplace well-being is needed. Design: The design of the study was qualitative and exploratory. Methods: Qualitative interview studies were conducted with 23 healthcare employees in municipal health care. Thematic analysis was used to analyse the data. Results: Two themes were identified as resources for promoting relationships between employees and care recipients or colleagues: (a) Being personal-a close interpersonal relationship to a care recipient-and (b) Colleague belongingness-a sense of togetherness within the working group. Spending quality time together, providing long-term care and providing additional care were prerequisites for a close interpersonal relationship with care recipients. Trust, mutual responsibility and cooperation were prerequisites for a sense of togetherness within the working group. Conclusions: The findings provide an empirical base to raise awareness of relationships with care recipients and colleagues as health aspects. Relationships among employees in health care are vital resources that must be considered to create sustainable workplaces and consequently improve the quality of care. Relevance to clinical practice: The results of this study advocate health promotion efforts based on interpersonal relationships at the workplace. Dialogues in the working groups, based on the employees' experiences of positive daily situations, may be a promoting method for the work-related well-being of the employees. (Less)

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

Background The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms. Methods Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2–52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3–51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE). Results Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p

IMPORTANCE: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden. OBJECTIVE: To examine the risk of serious infections associated with disease-modifying treatments for MS. DESIGN, SETTING, AND PARTICIPANTS: This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included. EXPOSURES: Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA. MAIN OUTCOMES AND MEASURES: Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions. RESULTS: A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]). CONCLUSIONS AND RELEVANCE: Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.

BACKGROUND: The resource use and health-related quality of life (HRQoL) of patients with multiple sclerosis (MS) spasticity are not well known. The purpose of this study was to obtain estimates of resource utilization, costs, and HRQoL, for patients with different levels of MS spasticity in southern Sweden. MATERIAL AND METHODS: Cross-sectional data on spasticity severity (using a Numerical Rating Scale, NRS), resource use and HRQoL (using EQ-5D) were collected using a patient questionnaire and chart review. Patients were recruited through a clinic in southern Sweden. The study reviews direct medical, direct non-medical and indirect costs. RESULTS: Total costs were estimated to €114,293 per patient and year. Direct medical costs (€7898) accounted for 7% of total costs. Direct non-medical costs (€68,509) accounted for 60% of total costs. Total costs increased with severity of spasticity: for patients with severe spasticity, the total cost was 2.4 times greater than those for patients with mild spasticity. HRQoL decreased as spasticity increases. CONCLUSION: The results of this study show that MS spasticity is associated with a substantial burden on society in terms of costs and HRQoL.

PurposeIn workplace health promotion, enhancing resources are less explored than risk factors. The aim of this paper is to explore the usability of the sense of coherence (SOC) theory to identify considerable and positively perceived work‐related factors and processes.Design/methodology/approachThe study had a salutogenic approach to workplace health promotion. A total of 13 focus group interviews were conducted with hospital employees in Sweden. A deductive analysis was made with the SOC theory as a framework.FindingsWork‐related specific enhancing resources (SER) were identified and analysed into the three components of SOC: comprehensibility, manageability, and meaningfulness. SER's implication in daily performance is explained by employee expressions. Through increased understanding and awareness, SER could contribute to savoring positive experiences, and enhance SOC among employees. Antonovsky's concept Generalized Resistance Resources is suggested to be enlarged based on the expressed significance of concrete daily positive work occurrences to increase one's SOC.Research limitations/implicationsNot all hospital professions were represented in the study. Further studies are required to involve physicians, paramedics, managers, as well as other settings, to compare and complement with additional experiences of workplace resources.Practical implicationsThe study presents an opportunity to explore, understand, and foster workplace resources through assistance from the SOC theory. The SER presented in this study may serve as initial examples in workplace discussions about work‐related resources contributing to a sense of coherence.Originality/valueThis study contributes to public health research and workplace health promotion with a salutogenic focus on how to explore enhancing work‐related resources with the assistance of the practical SOC theory.

Background In workplace health promotion, a questionnaire could be of great use. Unfortunately, fatigue regarding answering questionnaires has recently become greater than before. An action resear ...

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing–remitting MS patients ( n = 901), mean Expanded Disability Status Scale (EDSS, −10.7%), Multiple Sclerosis Severity Scale (MSSS, −20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical −9.9%, psychological −13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

Udgivelsesdato: 2009-May BACKGROUND: Tumefactive demyelinating disease (TDD) is a rare primary demyelinating disease with diagnostic and therapeutic challenges. METHODS AND RESULTS: We report a 50-year old woman with TDD successfully treated with decompressive craniectomy and corticosteroids. The patient presented with seizures, subacute progressive hemispheric syndrome, and a tumourlike abnormality on MRI. Demyelinating disease was initially considered unlikely. Due to a rapidly evolving herniation syndrome hemicraniectomy was performed. Outcome was favourable with only very mild neurological deficits 6 weeks later. CONCLUSION: TDD should be considered as a differential diagnosis in tumour-like presentations, and appears to have distinctive neuroimaging features. In the advent of treatement failure from high dose corticosteroids and plasmapheresis and development of severe mass effect, decompressive hemicraniectomy is an important treatment option.

The clinical applicability of the revised McDonald diagnostic criteria of primary progressive multiple sclerosis (PPMS) was assessed in 17 patients with a longstanding PPMS diagnosis (mean 15 years). All patients were re-evaluated with clinical examinations, magnetic resonance imaging (MRI) of the brain and the spinal cord, extensive laboratory tests, and 12 patients underwent cerebrospinal fluid (CSF) examination. No diagnosis more likely than PPMS was disclosed. All patients had brain and spinal cord lesions on MRI. In 15 patients the brain lesions and in 14 the spinal cord lesions fulfilled the revised McDonald criteria for positive scans. No contrast-enhancing lesion was observed despite administration of triple doses of gadolinium. In total, 12 patients fulfilled the revised McDonald MRI criteria for PPMS. Of the remaining five patients who incompletely fulfilled the revised MRI criteria, all had CSF findings supporting the diagnosis PPMS. Thus, CSF analysis was required in addition to MRI in about one-third of the patients to establish the diagnosis of PPMS. Udgivelsesdato: 2007-Nov

Background Multiple sclerosis ( MS) is a common disease with considerable risk for disability. Optic neuritis ( ON) is a common first symptom of MS but it can also remain an isolated episode. Therefore, predicting the outcome of ON has gained in importance, particularly in light of current discussions of early disease modifying treatments in individuals at risk of developing MS. We reported previously on our cohort of 86 patients with acute monosymptomatic unilateral ON of whom 33 had progressed to MS after up to 18 years. Three patients had died. The present study extends the observation period to 31 years. Methods Patients were followed for up to 31 years or until a diagnosis of MS was made. Cerebrospinal fluid (CSF) was examined at onset. HLA class I and II antigens were determined. Magnetic Resonance Imaging (MRI) was performed during follow up. Findings Only one of 50 patients at risk developed clinical manifestations of MS during the extended follow up period. The estimated 15-year-risk of MS was 40% ( confidence interval [CI] 31% - 52%). Most cases, 20 of 34 or 60%, occurred within three years. Among factors present at onset, CSF with mononuclear pleocytosis and/or oligoclonal Ig increased the risk for subsequent MS significantly, 49% (CI 38% - 65%) compared with 23% ( CI 12% - 44%) for those with normal CSF, p= 0.02. Younger patients and those with winter onset also had greater risk. Recurrence of ON similarly elevated the risk significantly, p< 0.001. After 19 - 31 years MRI lesions suggestive of demyelinating disease were detected in 20 of 30 individuals although no clinical manifestations of MS had occurred. Conclusion The risk of MS in this large population-based prospective ON patient series was 40% and significantly higher in those with inflammatory CSF abnormalities at onset. Clinically silent MRI lesions suggestive of MS were detected in a majority of those with "ON-only". This finding should be taken into account when discussing prognosis and early intervention in patients with clinically isolated ON. (Less)

Background Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS. Methods Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months. Results At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%). Conclusions HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

[Abstract] The intestinal lamina propria contains a dense network of T cells, dendritic cells (DCs) and macrophages, which play an important role in local innate and adaptive immune responses. We have recently identified distinct subsets of DCs (Persson et al., 2013) and macrophages (Bain et al., 2013) in the human intestine. In addition, we have studied T cells in healthy and diseased intestine. Here, we describe two methods for isolating these cell populations: 1) enzymatic treatment and 2) migration based isolation. The enzymatic method can be used to isolate T cells, DC and macrophages, whereas the migration based ‘walk-out’ protocol is suitable for DC isolation, as these cells migrate out from the tissues.

In workplace health promotion, a questionnaire could be of great use. Unfortunately, fatigue regarding answering questionnaires has recently become greater than before. An action research approach could be a possible way of increasing employee participation.This study reports an attempt to explore key aspects for participation in, and commitment to, a workplace health promotion questionnaire process.The study was conducted at two wards in a Swedish hospital. Data was collected during an action research process. Data were analysed with regard to a framework of questions.The three key aspects for participation in, and commitment to, a workplace health promotion questionnaire process were: an applicable questionnaire, a meaningful questionnaire process and a continuous and sustainable questionnaire process. A structure is presented as practical advice to managers, describing how such a process could be established to be applicable, meaningful and sustainable.This study has identified key aspects and prerequisites for questionnaire processes. The prerequisites - share decision-making, involve a core group and follow a structure - are discussed and proposed for managers and workgroups to consider in further workplace health promotion questionnaire processes.The key aspects and prerequisites presented could provide a stimulating standpoint or advice, useful for planning and accomplishing workplace questionnaire processes.

Objective Cognitive dysfunction is common in multiple sclerosis (MS), but long-term data on cognition in patients with clinically isolated syndromes are sparse. Methods We determined cognitive functions in 22 patients 44–75 years old diagnosed with optic neuritis 24–31 years earlier but had no further clinical bouts and had not progressed clinically to MS. We used a neuropsychological test battery covering nine cognitive domains. Magnetic resonance imaging (MRI) of the brain had been performed earlier and was normal in six patients and showed two or more white matter abnormalities compatible with demyelinating lesions in 16 patients. Results On neuropsychological testing, one patient was within normal range on all tests, six subjects showed borderline results, and 15 patients (68%) showed significantly impaired performance in at least one cognitive domain. Seven patients showed significant impairment in two or more domains. Executive function, visuo-spatial ability, and information processing speed were the most frequently affected domains. There was no apparent correlation between MRI findings and cognitive function. Conclusions We conclude that cognitive dysfunction is common in patients many years after clinically isolated optic neuritis. Cognitive dysfunction was found even in patients who had no apparent demyelinating lesions on follow-up MRI.

10-Formyltetrahydrofolate dehydrogenase is a ubiquitously expressed enzyme in the human body. It catalyses the formation of tetrahydrofolate and carbon dioxide from 10-­formyltetrahydrofolate, thereby playing an important role in the human metabolism of one-carbon units. It is a two-domain protein in which the N-terminal domain hydrolyses 10-formyltetrahydrofolate into formate and tetrahydrofolate. The high-resolution crystal structure of the hydrolase domain from human 10-formyltetrahydrofolate dehydrogenase has been determined in the presence and absence of a substrate analogue. The structures reveal conformational changes of two loops upon ligand binding, while key active-site residues appear to be pre-organized for catalysis prior to substrate binding. Two water molecules in the structures mark the positions of key oxygen moieties in the catalytic reaction and reaction geometries are proposed based on the structural data.

Transient global amnesia (TGA) occurs mostly in middle-aged and elderly individuals, and is generally believed to be very rare in individuals less than 40 years of age. We present three cases of TGA in young persons (16-22 years). They all had a medical history and presented symptoms fulfilling the criteria for TGA. Physical examinations and investigations were all normal. All three presented their symptoms while playing football. Reviewing the literature the suggested causes are partly different for TGA in old and young people, respectively. The present report confirms that TGA may also occur in younger individuals. We propose that single TGA is a benign condition also in younger persons and that the investigation should be similar to that of TGA in older age groups.

Creutzfeldt-Jakob disease (CJD) is a prion disease characterized by rapid neurodegeneration that leads to the death of the patient within months to a few years. Since the disease is transmissible, there is an obligation in Sweden to report possible CJD cases to the Swedish Institute for Infectious Disease Control. To make a diagnosis of CJD is difficult, especially early in the course of the disease when the clinical features may be very vague and heterogeneous. Hence, accurate biological markers both for confirming and excluding CJD would be of great value. The currently recommended investigation of a patient with possible CJD comprises clinical evaluation. electroencephalography, computed tomography or magnetic resonance imaging of the brain and test for 14-3-3 protein in the cerebrospinal fluid (CSF). Recent studies suggest that analysis of total tau (T-tau) and phospho-tau (P-tau) in CSF is a valuable complement to this set of investigations. Here, we review how CSF T-tau and P-tau may aid in the diagnosis of CJD and illustrate this by presenting cases from routine clinical practice.