| 1. |
- Grut, Viktor, et al.
(författare)
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Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis
- 2024
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 147:1, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.
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| 2. |
- Koppner, Jenny, et al.
(författare)
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Factors affecting self-perceived mental health in the general older population during the COVID-19 pandemic: a cross-sectional study
- 2024
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Ingår i: BMC Public Health. - : BMC. - 1471-2458. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Mental health problems among older people are large public health concerns but often go unrecognized and undertreated. During COVID - 19 several restrictions regarding social contacts were launched, primarily for the old. The objective of this study is to investigate which factors that had the main negative affect on mental health in the older population during the pandemic. Method A cross-sectional cohort study set in Swedish primary care during the pandemic years 2021-2022. The population constitutes of 70-80-years-old, N = 260. Instruments used are Geriatric depression scale 20 (GDS20); Hospital anxiety and depression scale (HADS), and Perceived stress scale 10 (PSS10). Sociodemography and risk factors are explored. Outcome measures are factors independently associated with decreased mental health. Analyses were performed for the group as a whole and with logistic regression models comparing individuals who stated they were mentally affected by the pandemic to individuals who stated they were not. Results Participants who stated they were mentally affected by the COVID - 19 pandemic reported significantly higher levels of anxiety (p < 0.001), depression (p < 0.001), and stress (p = 0.026) compared to those who stated they were not mentally affected. Explanatory regression models of up to 50% showed that following factors were prominent among individuals who reported a decline in their mental health due to the COVID - 19 pandemic (n = 24); impaired social life (OR 20.29, p < 0.001, CI 4.53-90.81), change in physical activity (OR 5.28, p = 0.01, CI 1.49-18.72), perceived family situation (OR 31.90, p = 0,007, CI 2,53-402.42), mild/moderate and high anxiety (OR 4.94, p = 0.034, CI 1.13-21.60, OR 7.96, p = 0.035, CI 1.16-54.53 respectively), and female gender (OR 6.52, p = 0.029, CI 1.22-34.92). Conclusion Anxiety, family situation, social life and change in physical activity were the main factors influencing the 70-80-years-old's self-perceived mental health during the COVID - 19 pandemic. Long-term effects of social restrictions on mental health in the older population need to be further investigated.
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| 3. |
- Andreae, Christina, 1969-, et al.
(författare)
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Does problem-based learning improve patient empowerment and cardiac risk factors in patients with coronary heart disease in a Swedish primary care setting? : A long-term prospective, randomised, parallel single randomised trial (COR-PRIM)
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate long-term effects of a 1-year problem-based learning (PBL) on self-management and cardiac risk factors in patients with coronary heart disease (CHD).Design: A prospective, randomised, parallel single centre trial.Settings: Primary care settings in Sweden.Participants: 157 patients with stable CHD completed the study. Subjects with reading and writing impairments, mental illness or expected survival less than 1 year were excluded.Intervention: Participants were randomised and assigned to receive either PBL (intervention) or home-sent patient information (control group). In this study, participants were followed up at baseline, 1, 3 and 5 years.Primary and secondary outcomes: Primary outcome was patient empowerment (Swedish Coronary Empowerment Scale, SWE-CES) and secondary outcomes General Self-Efficacy Scale (GSES), self-rated health status (EQ-VAS), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), weight and smoking. Outcomes were adjusted for sociodemographic factors.Results: The PBL intervention group resulted in a significant improved change in SWE-CES over the 5-year period (mean (M), 39.39; 95% CI 37.88 to 40.89) compared with the baseline (M 36.54; 95% CI 35.40 to 37.66). PBL intervention group increased HDL-C level (M 1.39; 95% CI 1.28 to 1.50) compared with baseline (M 1.24; 95% CI 1.15 to 1.33) and for EQ-VAS (M 77.33; 95% CI 73.21 to 81.45) compared with baseline (M 68.13; 95% CI 63.66 to 72.59) while these outcomes remained unchanged in the control group. There were no significant differences in BMI, weight or scores on GSES, neither between nor within groups over time. The overall proportion of smokers was significantly higher in the control group than in the experimental group.Conclusion: One-year PBL intervention had positive effect on patient empowerment, health status and HDL-C at a 5-year follow-up compared with the control group. PBL education aiming to improve patient empowerment in cardiac rehabilitation should account for sociodemographic factors.
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| 4. |
- Antera, Sofia, 1992-
(författare)
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Vocational Teachers’ Professional Competence at the Intersection of Two Regimes of Competence : The case of Sweden
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The high demand for vocational teachers in Vocational Education and Training (VET) in Sweden has led to their recruitment in the early stages of vocational teacher studies. Entering into this new community of practice, vocational teachers tend to bring in experience from their previous occupational practice. This dissertation explores vocational teachers’ competence through their own perceptions and through the school principals’ perspective, addressing important competence areas, as well as how professional competence is defined and understood by vocational teachers themselves.This dissertation is a compilation thesis of three Studies. Study I is a Conceptual Analysis Method (CAM) of the concept of professional competence of vocational teachers. Study I demonstrated that the main attributes of professional competence include the situated and developmental character of professional competence and its relationship with action. A distinct relationship between professional competence and professionalism, performance, and qualifications was identified as significant to the concept.Study II, a questionnaire of important and achieved competence, answered by 370 participants, showed that good communication with students and assessment of students’ knowledge, skills and abilities are the two most important and achieved competencies for vocational teachers. On the contrary, previous teaching experience and working experience with migrants were placed among the least important. Moreover, Study II presented results on vocational teachers’ challenges, with students that need extra support being the challenge affecting teachers the most.Study III, an interview study with 14 vocational teachers, outlined the regime of competence for vocational teachers. The regime of competence is a set of principles that recognise membership in a community. According to the findings, the regime of competence for vocational teachers includes up-to-date vocational competence, but also interpersonal competence, meaning communication skills and the construction of a teacher-student trust relationship. Part of this regime is also the teacher’s ability to match the student with the workplace, contributing to higher quality work-based training for the student. Finally, a continuous development attitude is included.The combined findings from the three Studies indicated that teaching competence has a high use value due to its relevance with the vocational teachers’ work, but low exchange value as it is not a formal requirement for teachers’ employment. On the contrary, vocational competence have high exchange value, as it is required for recruitment. The analysis of the combined findings concluded that different competence areas are prioritised based on relevance to the teaching practice, formality and individual preference. With these three aspects affecting teachers’ choices of what competence they would develop, there is a risk for unbalanced identities.In conclusion, understanding what is needed for the job of a vocational teacher can facilitate better preparation for vocational teachers. Supporting teachers aligning their previous competence with the regime of competence instructed by the practice of vocational teaching can be assisted through the recontextualisation of previous experiences to achieve relevance to the new tasks.
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| 5. |
- Böhmer, Jens, 1981, et al.
(författare)
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Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study.
- 2023
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874 .- 1432-2277. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14 days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.
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| 6. |
- Edén, Arvid, 1975, et al.
(författare)
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Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection
- 2023
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. Methods We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or >= 3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). Results In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4(+) T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or >= 3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4(+) T-cell strata after 1 or >= 3 (median, 6.6) years of ART. Conclusions In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.
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| 7. |
- Gudmundsdottir, J. A., et al.
(författare)
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Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis
- 2023
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T-and B-cell output at birth, in patients with early onset JIA.Methods: TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2-5 days after birth, in 156 children with early onset JIA and in 312 matched controls.Results: When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55-113) in JIA cases and 88 (IQR 57-117) copies/well in controls. The median KREC level was 51 (IQR 35-69) and 53 (IQR 35-74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs.Conclusion: T-and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls.
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| 8. |
- Hellgren, Mikko, 1972-, et al.
(författare)
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Hypertension management in primary health care : a survey in eight regions of Sweden
- 2023
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis. - 0281-3432 .- 1502-7724. ; 41:3, s. 343-350
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore hypertension management in primary healthcare (PHC).Design: Structured interviews of randomly selected PHC centres (PHCCs) from December 2019 to January 2021.Setting: Seventy-six PHCCs in eight regions of Sweden.Main outcome measures: Staffing and organization of hypertension care. Methods of measuring blood pressure (BP), laboratory tests, registration of co-morbidities and lifestyle advice at diagnosis and follow-up.Results: The management of hypertension varied among PHCCs. At diagnosis, most PHCCs (75%) used the sitting position at measurements, and only 13% routinely measured standing BP. One in three (33%) PHCCs never used home BP measurements and 25% only used manual measurements. The frequencies of laboratory analyses at diagnosis were similar in the PHCCs. At follow-up, fewer analyses were performed and the tests of lipids and microalbuminuria decreased from 95% to 45% (p < 0.001) and 61% to 43% (p = 0.001), respectively. Only one out of 76 PHCCs did not measure kidney function at routine follow-ups. Lifestyle, physical activity, food habits, smoking and alcohol use were assessed in & GE;96% of patients at diagnosis. At follow-up, however, there were fewer assessments. Half of the PHCCs reported dedicated teams for hypertension, 82% of which were managed by nurses. There was a great inequality in the number of patients per tenured GP in the PHCCs (median 2500; range 1300-11300) patients.Conclusions: The management of hypertension varies in many respects between PHCCs in Sweden. This might lead to inequity in the care of patients with hypertension.
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| 9. |
- Jons, Daniel, et al.
(författare)
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Epstein-Barr virus seroreactivity, putative autoimmunity and axonal injury in pre-symptomatic multiple sclerosis
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 39-40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Multiple sclerosis (MS) and presymptomatic axonal injury appears to develop only after an Epstein-Barr virus (EBV) infection. Anoctamin2 (ANO2), a chloride channel expressed in glial cells and neurons, was identified as a possible MS autoantigen. We here examine serum neurofilament (sNfL), a comprehensive EBV seroreactivity and antibodies against ANO2 in pre-symptomatic MS.Objectives/Aims: To study whether the appearance of EBV seroreactivity in the pre-symptomatic phase of MS precedes cumulating MS-induced neuroaxonal damage and whether it is associated with an incipient autoreactivity against a reported MS autoantigen (ANO2).Methods: We performed a case-control study with presymptomatic serum samples identified through cross-linkage of the Swedish MS register and Swedish biobanks. We assayed serum antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18 (VCAp18), EBV glycoprotein 350 (gp350), anoctamin 2 (ANO2), and serum neurofilament light (sNfL) in 669 pre-MS cases and matched controls.Results: EBNA1 seroreactivity increased in the pre-MS group from 20–15 years before MS onset, followed by gp350 seroreactivity (p=0.001–0.002, 15–10 years before onset). This appeared before the elevation of sNfL in EBV seropositive pre-MS cases (p=8⋅10-5, 10–5 years before onset). No significant sNfL increase was observed in the EBV seronegative group (p=0.95). Pre-MS cases with the highest sNfL levels cumulated in the EBV seropositive group (p=0.038). ANO2 seropositivity appeared virtually only in the EBNA1 seropositive group, in 16.7 % of EBNA1 seropositive pre-MS samples and in 10.0 % of corresponding controls (p=0.001). Combined EBNA1 and ANO2 seropositivity showed a higher association with subsequent MS than EBNA1 independent of ANO2 (p=0.002–0.028). In the EBNA1 seropositive stratum, ANO2 seropositivity was associated with 26% higher sNfL.Conclusion: In presymptomatic MS an antibody response against EBV, associated with ANO2 autoimmunity, was detectable before elevated sNfL, which cumulated in the EBV seropositive group. ANO2 seropositivity was associated with higher sNfL. An increase in ANO2 seroreactivity did not appear until after EBV seroconversion, limited to a subgroup of the EBV seropositive stratum. Thus, this specific cross-reaction could contribute to MS pathogenesis in a subgroup. This further implicates EBV in the pathogenesis of MS.
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| 10. |
- Jons, Daniel, et al.
(författare)
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Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
- 2023
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 1468-330X .- 0022-3050.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
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