| 1. |
- Allahyari, Ali, et al.
(author)
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Low-density lipoprotein-cholesterol target attainment according to the 2011 and 2016 ESC/EAS dyslipidaemia guidelines in patients with a recent myocardial infarction : nationwide cohort study, 2013–17
- 2021
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In: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 7:1, s. 59-67
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Journal article (peer-reviewed)abstract
- AIMS: To assess low-density lipoprotein cholesterol (LDL-C) treatment target attainment among myocardial infarction (MI) patients according to the ESC/EAS dyslipidaemia guidelines from 2011 (LDL-C <1.8 mmol/L or ≥ 50% LDL-C reduction) and 2016 (LDL-C <1.8 mmol/L and ≥50% LDL-C reduction).METHODS AND RESULTS: Using nationwide registers, we identified 44,890 patients aged 21-74 admitted for MI, 2013-2017. We included those attending follow-up visits at 6-10 weeks (n = 25,466) and 12-14 months (n = 17,117) after the event. Most patients received high-intensity statin monotherapy (84.3% [6-10 weeks] and 69.0% [12-14 months]) or statins with ezetimibe (2.7% and 10.2%). The proportion of patients attaining the 2011 LDL-C target was 63.8% (6-10 weeks) and 63.5% (12-14 months). The corresponding numbers for the 2016 LDL-C target was 31.6% (6-10 weeks) and 31.5% (12-14 months). At the 6-10-week follow-up, 37% of those not attaining the 2011 LDL-C target and 48% of those not attaining the 2016 target had an LDL-C level that was ≥0.5 mmol/L from the target. When comparing LDL-C measurements performed before vs. after the release of the 2016 guidelines, attainment of the 2016 LDL-C target increased from 30.2% to 35.0% (6-10 weeks) and from 27.6% to 37.6% (12-14 months).CONCLUSIONS: In a nationwide register, one out of three patients with a recent MI had not attained the LDL-C target of the 2011 ESC/EAS guidelines and two out of three patients had not attained the LDL-C target of the 2016 guidelines.
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| 2. |
- Ambrosi, Aurelie, et al.
(author)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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In: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Journal article (peer-reviewed)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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| 8. |
- Golovliov, Igor, 1958-, et al.
(author)
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Long-Term Survival of Virulent Tularemia Pathogens outside a Host in Conditions That Mimic Natural Aquatic Environments
- 2021
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In: Applied and Environmental Microbiology. - : Elsevier. - 0099-2240 .- 1098-5336. ; 87:6, s. 1-11
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Journal article (peer-reviewed)abstract
- Francisella tularensis, the causative agent of the zoonotic disease tularemia, can cause seasonal outbreaks of acute febrile illness in humans with disease peaks in late summer to autumn. Interestingly, its mechanisms for environmental persistence between outbreaks are poorly understood. One hypothesis is that F. tularensis forms biofilms in aquatic environments. We utilized two fully virulent wild-type strains: FSC200 (Francisella tularensis subsp. holarctica) and Schu S4 (Francisella tularensis subsp. tularensis) and three control strains, the attenuated live vaccine strain (LVS; F. tularensis subsp. holarctica), a Schu S4 DwbtI mutant that is documented to form biofilms, and the low-virulence strain U112 of the closely related species Francisella novicida. Strains were incubated in saline solution (0.9% NaCl) microcosms for 24 weeks at both 4°C and 20°C, whereupon viability and biofilm formation were measured. These temperatures were selected to approximate winter and summer temperatures of fresh water in Scandinavia, respectively. U112 and Schu S4 DwbtI formed biofilms, but F. tularensis strains FSC200 and Schu S4 and the LVS did not. All strains exhibited prolonged viability at 4°C compared to 20°C. U112 and FSC200 displayed remarkable long-term persistence at 4°C, with only 1- and 2-fold log reductions, respectively, of viable cells after 24weeks. Schu S4 exhibited lower survival, yielding no viable cells by week 20. At 24weeks, cells from FSC200, but not from Schu S4, were still fully virulent in mice. Taken together, these results demonstrate biofilm-independent, long-term survival of pathogenic F. tularensis subsp. holarctica in conditions that mimic overwinter survival in aquatic environments.
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| 9. |
- Jonsson, Emma, et al.
(author)
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Swedish osteoporosis care
- 2015
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In: ARCHIVES OF OSTEOPOROSIS. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 10:1
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Journal article (peer-reviewed)abstract
- Mini-abstract The objective of this study was to review and describe the current state of Swedish osteoporosis care and to highlight ongoing challenges. This report encompasses quantitative health outcomes based on Swedish registry data as well as organizational and management aspects. Executive summary Swedish osteoporosis care is characterized by a significant burden of disease, difficulties in identifying high-risk patients, and fragmented pathways for patients in need of secondary fracture prevention. This report aimed to describe the current state, gaps, and challenges in Swedish osteoporosis care, using Swedish national databases, questionnaires, and interviews with healthcare representatives. A secondary aim was to develop quality and process measures to compare differences between counties and to use those measures to describe the interaction between quantitative health outcomes and aspects of care organization and management. In conjunction with fractures, a considerably smaller proportion of men are treated than women, and a smaller proportion of older women are treated compared to younger groups. Between 3 and 16 % of patients receive treatment after a fracture, and the treatment rate in this patient group can likely increase. In addition to an unsatisfactory treatment rate, a limited number of those treated continue treatment throughout the recommended treatment durations, leading to increased risk of fracture. With a substantial variation between counties, there is a clear difficulty to identify non-persistent patients and switch to an alternative treatment. Collaboration around the patient across specialties has been lacking, and systems for secondary prevention have been concentrated to a few counties. However, when this study was conducted, there was a general trend towards implementing regional care programs. This report suggests possible strategies for improving quality of care and, hopefully, it can provide a basis for future evaluations and regional improvement of osteoporosis care in Sweden and other countries.
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| 10. |
- Meisgen, Sabrina, et al.
(author)
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The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence
- 2014
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:6, s. 640-651
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases, and 95 unaffected siblings).RESULTS: A case-control comparison between index cases and population-based out-of-study controls (n=1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of p<2.59×10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more frequently transmitted to affected individuals (p<0.03 and p<0.05, respectively), while HLA-DRB1*13 and HLA-Cw*06 variants were significantly less often transmitted to affected children (p<0.04 and p<0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB1*04 transmission to affected offspring (p<0.02).CONCLUSIONS: HLA-DRB1*04 and HLA-Cw*05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, while DRB1*13 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.
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| 11. |
- Mohanty, Salini, et al.
(author)
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Increased risk of long-term disabilities following childhood bacterial meningitis in Sweden
- 2024
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In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:1
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Journal article (peer-reviewed)abstract
- IMPORTANCE: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort.OBJECTIVE: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden.DESIGN, SETTING, AND PARTICIPANTS: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023.EXPOSURE: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021.MAIN OUTCOMES AND MEASURES: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood.RESULTS: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median.CONCLUSIONS AND RELEVANCE: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.
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| 12. |
- Salomonsson, Stina, et al.
(author)
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Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block
- 2005
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 201:1, s. 11-17
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Journal article (peer-reviewed)abstract
- Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers. The condition is often fatal and the majority of live-born children require a pacemaker at an early age. The specific antibody that induces the heart block and the mechanism by which it mediates the pathogenic effect have not been elucidated. In this study, we define the cellular mechanism leading to the disease and show that maternal autoantibodies directed to a specific epitope within the leucine zipper amino acid sequence 200–239 (p200) of the Ro52 protein correlate with prolongation of fetal atrioventricular (AV) time and heart block. This finding was further confirmed experimentally in that pups born to rats immunized with p200 peptide developed AV block. p200-specific autoantibodies cloned from patients bound cultured cardiomyocytes and severely affected Ca2+ oscillations, leading to accumulating levels and overload of intracellular Ca2+ levels with subsequent loss of contractility and ultimately apoptosis. These findings suggest that passive transfer of maternal p200 autoantibodies causes congenital heart block by dysregulating Ca2+ homeostasis and inducing death in affected cells.
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| 13. |
- Salomonsson, Stina
(author)
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The role of Ro52 autoantibodies in congenital heart block
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The presence of B cells producing autoantibodies is a common feature of many autoimmune conditions. The pathogenic role of the autoantibodies is often unclear, but they often serve as diagnostic markers and may be used as prognostic tools in some diseases. This thesis addresses the production of anti-Ro52 antibodies in patients with Sjögren's syndrome, and their pathogenic effect in the fetus after transplacental transport during pregnancy. The autoimmune inflammation in Sjögren's syndrome targets exocrine organs. Lymphocytic infiltrates develop in the salivary glands, and within these infiltrates germinal center-like structures may develop. In the initial studies of this thesis the molecular requirements for lymphocyte recruitment to the salivary glands, as well as morphological and functional properties of the germinal center-like structures were investigated. Chronically inflamed salivary glands exhibited an increased expression of adhesion molecules (VCAM- 1, VLA-4, ICAM-1 and LFA- 1), detected on endothelium an infiltrating mononuclear cells. In addition, B and T cell-attracting chemokines (CXCL1 3, CCL21 and CXCL12) were expressed by epithelial cells in the glands, and the chemokine receptor (CXCR5) was detected on infiltrating lymphocytes. Networks of follicular dendritic cells were demonstrated throughout the large infiltrates, while autoantibody-producing plasma cells and apoptotic cells were mainly localized to the margins of these infiltrates. The presented studies provide a molecular basis for lymphocyte-recruitment to the target organ and demonstrate functional ectopic germinal centers with local autoantibody production in the target organ. These structures might actively promote chronic inflammation, and differences in the microenvironment and structure compared to ordinary germinal centers might contribute to a disturbance in the selection process allowing autoreactive clones to develop more frequently. During pregnancy Ro52 antibodies are tranfered to the fetus, which may lead to development of congenital heart block. Although rare, the condition is often fatal and the majority of live borns require a pacemaker at an early age. To elucidate the pathogenic importance of anti-Ro52 antibodies in the course of congenital heart block, their role was investigated in vivo in pregnant women and in a murine model for the disease, as well as in vitro in primary rat cardiomyocyte cultures. Seropositive pregnant women were prospectively followed and fetal progression monitored using Doppler echocardiography. One-third of the fetuses developed a transcient AV block 1, demonstrating that fetal affection is far more common than previously appreciated. The study also revealed congenital heart block develops gradually, a finding essential for therapeutic decisions and understanding of the underlying pathogenic mechanism. Thorough epitope mapping of the humoral response in pregnant women with anti-Ro52 antibodies revealed a specific serologic marker associated with fetal heart block, a finding enabling risk assessment and increasing the chances for early detection of block and successful fetal outcome. The specific antibodies associated with block were cloned and demonstrated to bind to the cell surface of neonatal cardionryocytes in vitro, dysregulating Ca 21 homeostasis, leading to accumulating intracellular levels of Ca 2+ and eventually inducing apoptosis. The pathogenic effect of the antibodies was verified in a murine model for congenital heart block. In conclusion, our results have led to the proposal of a mechanism for development of congenital heart block in which specific maternal anti-Ro52 antibodies have a central pathogenic role through interaction with fetal cardiomyocytes, affecting their function and resulting in a permanent cardiac insult.
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| 14. |
- Wagenius, Gunnar, et al.
(author)
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First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden : A Population-based Real-world Study with Focus on Immunotherapy
- 2024
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 63, s. 198-205
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. MATERIALS AND METHODS: Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. RESULTS: A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. INTERPRETATION: The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.
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| 15. |
- Wimo, Anders, et al.
(author)
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Quantifying and Describing the Natural History and Costs of Alzheimer's Disease and Effects of Hypothetical Interventions
- 2020
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In: Journal of Alzheimer's Disease. - : IOS PRESS. - 1387-2877 .- 1875-8908. ; 75:3, s. 891-902
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Journal article (peer-reviewed)abstract
- Background: A long-term horizon is necessary when the socioeconomic consequences and the potential effects of interventions in Alzheimer's disease (AD) are estimated. Objectives: To illustrate the potential societal costs of AD across the disease continuum and to illustrate the potential cost-effectiveness of a hypothetical intervention with disease modifying treatment (DMT). Methods: Based on the Swedish dementia registry, a Markov model was used to simulate a virtual cohort of 100,000 people with mild cognitive impairment (MCI) due to AD (AD-MCI) in Sweden for 40 years starting at the age of 60. A simulated hypothetical intervention assumed a 25% reduction in progression rate during AD-MCI and mild AD-dementia. A comprehensive set of sensitivity analyses was included. Results: The cumulative risk to develop dementia was 96%. The mean simulated survival was 19.0 years. The net present value for a person year with dementia was 252,843 SEK (about 29,500 US$). The cost effectiveness model illustrated how the hypothetical scenario of a 25% reduction in progression to AD-dementia would require 41 AD-MCI patients to be treated to prevent one case of AD-dementia (2,447 avoided AD-dementia cases of 100,000 with AD-MCI). Most scenarios illustrated hypothetical cost effectiveness (based on a willingness to pay level of 600,000 SEK (70,000 US$) per gained QALY), but not cost savings. Discussion: Lifetime societal costs of AD are substantial. A future DMT may be potentially cost-effective given assumed treatment effects and costs, but cost savings are unlikely.
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