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Sökning: WFRF:(Lehtonen H)

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  • Sliz, E., et al. (författare)
  • Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
  • 2023
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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  • Tabassum, R, et al. (författare)
  • Genetic architecture of human plasma lipidome and its link to cardiovascular disease
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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  • van der Plas, F., et al. (författare)
  • Continental mapping of forest ecosystem functions reveals a high but unrealised potential for forest multifunctionality
  • 2018
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 21:1, s. 31-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Humans require multiple services from ecosystems, but it is largely unknown whether trade-offs between ecosystem functions prevent the realisation of high ecosystem multifunctionality across spatial scales. Here, we combined a comprehensive dataset (28 ecosystem functions measured on 209 forest plots) with a forest inventory dataset (105,316 plots) to extrapolate and map relationships between various ecosystem multifunctionality measures across Europe. These multifunctionality measures reflected different management objectives, related to timber production, climate regulation and biodiversity conservation/recreation. We found that trade-offs among them were rare across Europe, at both local and continental scales. This suggests a high potential for win-win' forest management strategies, where overall multifunctionality is maximised. However, across sites, multifunctionality was on average 45.8-49.8% below maximum levels and not necessarily highest in protected areas. Therefore, using one of the most comprehensive assessments so far, our study suggests a high but largely unrealised potential for management to promote multifunctional forests.
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  • Kambach, S., et al. (författare)
  • How do trees respond to species mixing in experimental compared to observational studies?
  • 2019
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:19, s. 11254-11265
  • Tidskriftsartikel (refereegranskat)abstract
    • For decades, ecologists have investigated the effects of tree species diversity on tree productivity at different scales and with different approaches ranging from observational to experimental study designs. Using data from five European national forest inventories (16,773 plots), six tree species diversity experiments (584 plots), and six networks of comparative plots (169 plots), we tested whether tree species growth responses to species mixing are consistent and therefore transferrable between those different research approaches. Our results confirm the general positive effect of tree species mixing on species growth (16% on average) but we found no consistency in species-specific responses to mixing between any of the three approaches, even after restricting comparisons to only those plots that shared similar mixtures compositions and forest types. These findings highlight the necessity to consider results from different research approaches when selecting species mixtures that should maximize positive forest biodiversity and functioning relationships.
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  • Saarikangas, J, et al. (författare)
  • Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia
  • 2011
  • Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 124:8Pt 8, s. 1245-1255
  • Tidskriftsartikel (refereegranskat)abstract
    • MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
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  • Kujala, M, et al. (författare)
  • SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney
  • 2005
  • Ingår i: Nephron. Experimental nephrology. - : S. Karger AG. - 1660-2129. ; 101:2, s. E50-E58
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> The anion transporters SLC26A6 (PAT1) and SLC26A7, transporting at least chloride, oxalate, sulfate and bicarbonate, show a distinct expression and function in different mammalian species. They are expressed in kidney, but their exact localization in human kidney has not been studied. We therefore examined SLC26A6 and A7 expression in human kidneys. <i>Methods:</i> The localization of SLC26A6 and A7 in different segments of human nephrons was studied by RT-PCR and immunohistochemistry by comparing to the tubular markers PNRA, CD10, Tamm-Horsfall antigen, high molecular weight cytokeratin, CK7, AQP2 and H<sup>+</sup>V-ATPase. <i>Results:</i> In human kidney, SLC26A6 is expressed in distal segments of proximal tubules, parts of the thin and thick ascending limbs of Henle’s loops, macula densa, distal convoluted tubules and a subpopulation of intercalated cells of collecting ducts. SLC26A7 is expressed in extraglomerular mesangial cells and a subpopulation of intercalated cells of collecting ducts. <i>Conclusion:</i> Our results show that in human kidney SLC26A6 and A7 have a distinct, partially overlapping expression in distal segments of nephrons. The distribution partly differs from that found previously in rodent kidneys.
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  • Pulkka, OP, et al. (författare)
  • Anagrelide for Gastrointestinal Stromal Tumor
  • 2019
  • Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 25:5, s. 1676-1687
  • Tidskriftsartikel (refereegranskat)
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  • Turja, R., et al. (författare)
  • A multibiomarker approach to the assessment of pollution impacts in two Baltic Sea coastal areas in Sweden using caged mussels (Mytilus trossulus)
  • 2014
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 473, s. 398-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Blue mussels (Mytilus trossulus) were transplanted in cages for three months in two Swedish coastal areas in the Bothnian Sea (northern Baltic Sea) to investigate the interactions between analysed environmental chemicals and biological responses. A wide array of biological parameters (biomarkers) including antioxidant and biotransformation activity, geno-, cyto- and neurotoxic effects, phagocytosis, bioenergetic status and heart rate were measured to detect the possible effects of contaminants. Integrated Biomarker Response index and Principal Component Analysis performed on the individual biological response data were able to discriminate between the two study areas as well as the contaminated sites from their respective local reference sites. The two contaminated sites outside the cities of Sundsvall (station 51) and Gavle (station G1) were characterised by different biomarker response patterns. Mussels at station S1 showed a low condition index, increased heart rate recovery time and phagocytosis activity coinciding with the highest tissue concentrations of some trace metals, polycyclic aromatic hydrocarbons and organotins. At station G1 the highest organochlorine pesticide concentration was recorded as well as elevations in glutathione S-transferase activity, thiamine content and low lysosomal membrane stability. Significant variability in the geno- and cytotoxic responses and bioenergetic status was also observed at the different caging stations. The results obtained suggest that different chemical mixtures present in the study areas cause variable biological response patterns in organisms.
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  • Zhao, L, et al. (författare)
  • Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs
  • 2023
  • Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.
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  • Agustin, Melissa B., et al. (författare)
  • Enzymatic crosslinking of lignin nanoparticles and nanocellulose in cryogels improves adsorption of pharmaceutical pollutants
  • 2024
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 266
  • Tidskriftsartikel (refereegranskat)abstract
    • Pharmaceuticals, designed for treating diseases, ironically endanger humans and aquatic ecosystems as pollutants. Adsorption-based wastewater treatment could address this problem, however, creating efficient adsorbents remains a challenge. Recent efforts have shifted towards sustainable bio-based adsorbents. Here, cryogels from lignin-containing cellulose nanofibrils (LCNF) and lignin nanoparticles (LNPs) were explored as pharmaceuticals adsorbents. An enzyme-based approach using laccase was used for crosslinking instead of fossil-based chemical modification. The impact of laccase treatment on LNPs alone produced surface-crosslinked water-insoluble LNPs with preserved morphology and a hemicellulose-rich, water-soluble LNP fraction. The water-insoluble LNPs displayed a significant increase in adsorption capacity, up to 140 % and 400 % for neutral and cationic drugs, respectively. The crosslinked cryogel prepared by one-pot incubation of LNPs, LCNF and laccase showed significantly higher adsorption capacities for various pharmaceuticals in a multi-component system than pure LCNF or unmodified cryogels. The crosslinking minimized the leaching of LNPs in water, signifying enhanced binding between LNPs and LCNF. In real wastewater, the laccase-modified cryogel displayed 8–44 % removal for cationic pharmaceuticals. Overall, laccase treatment facilitated the production of bio-based adsorbents by improving the deposition of LNPs to LCNF. Finally, this work introduces a sustainable approach for engineering adsorbents, while aligning with global sustainability goals.
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  • Ahola, Virpi, et al. (författare)
  • The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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  • Artigas, J., et al. (författare)
  • Towards a renewed research agenda in ecotoxicology
  • 2012
  • Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 160, s. 201-206
  • Tidskriftsartikel (refereegranskat)abstract
    • New concerns about biodiversity, ecosystem services and human health triggered several new regulations increasing the need for sound ecotoxicological risk assessment. The PEER network aims to share its view on the research issues that this challenges. PEER scientists call for an improved biologically relevant exposure assessment. They promote comprehensive effect assessment at several biological levels. Biological traits should be used for Environmental risk assessment (ERA) as promising tools to better understand relationships between structure and functioning of ecosystems. The use of modern high throughput methods could also enhance the amount of data for a better risk assessment. Improved models coping with multiple stressors or biological levels are necessary to answer for a more scientifically based risk assessment. Those methods must be embedded within life cycle analysis or economical models for efficient regulations. Joint research programmes involving humanities with ecological sciences should be developed for a sound risk management. (C) 2011 Elsevier Ltd. All rights reserved.
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  • Huhtala, V, et al. (författare)
  • Low plasma cholecystokinin levels in colicky infants
  • 2003
  • Ingår i: Journal of pediatric gastroenterology and nutrition. - : Ovid Technologies (Wolters Kluwer Health). - 0277-2116. ; 37:1, s. 42-46
  • Tidskriftsartikel (refereegranskat)
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  • Jaaskelainen, T, et al. (författare)
  • A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants
  • 2018
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 14616-
  • Tidskriftsartikel (refereegranskat)abstract
    • Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.
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  • Jarvilehto, J., et al. (författare)
  • Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy
  • 2022
  • Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo characterize serum biomarkers in mitochondrial CHCHD10-linked spinal muscular atrophy Jokela (SMAJ) type for disease monitoring and for the understanding of pathogenic mechanisms. MethodsWe collected serum samples from a cohort of 49 patients with SMAJ, all carriers of the heterozygous c.197G>T p.G66V variant in CHCHD10. As controls, we used age- and sex-matched serum samples obtained from Helsinki Biobank. Creatine kinase and creatinine were measured by standard methods. Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with single molecule array (Simoa), fibroblast growth factor 21 (FGF-21), and growth differentiation factor 15 (GDF-15) with an enzyme-linked immunosorbent assay. For non-targeted plasma metabolite profiling, samples were analyzed with liquid chromatography high-resolution mass spectrometry. Disease severity was evaluated retrospectively by calculating a symptom-based score. ResultsAxon degeneration marker, NfL, was unexpectedly not altered in the serum of patients with SMAJ, whereas astrocytic activation marker, GFAP, was slightly decreased. Creatine kinase was elevated in most patients, particularly men. We identified six metabolites that were significantly altered in serum of patients with SMAJ in comparison to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine, and succinate. Creatine correlated with disease severity. Altered pyruvate and succinate indicated a metabolic response to mitochondrial dysfunction; however, lactate or mitochondrial myopathy markers FGF-21 or GDF-15 was not changed. ConclusionsBiomarkers of muscle mass and damage are altered in SMAJ serum, indicating a role for skeletal muscle in disease pathogenesis in addition to neurogenic damage. Despite the minimal mitochondrial pathology in skeletal muscle, signs of a metabolic shift can be detected.
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  • Kaasinen, E, et al. (författare)
  • Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
  • Tidskriftsartikel (refereegranskat)abstract
    • Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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  • Kohlmann, Johannes, et al. (författare)
  • A quantum standard for sampled electrical measurements-Main goals and first results of the EMRP project Q-WAVE
  • 2014
  • Ingår i: 29th Conference on Precision Electromagnetic Measurements, CPEM 2014. ; , s. 522-523
  • Konferensbidrag (refereegranskat)abstract
    • Josephson voltage standards are well established for use at dc and low-frequency ac voltages. The increasing demand i) to provide traceability for arbitrary waveforms, ii) to extend the range of use to higher frequencies, and iii) to improve the accuracy is being addressed in the project Q-WAVE, which is jointly funded by the European Union and the participating countries within the European Metrology Research Programme (EMRP). Here, sampling measurements and procedures using binary-divided 1 V and 10 V arrays are investigated. In addition, a quantum-based analogue-to-digital converter for direct measurements of arbitrary waveforms is under development. It will contain several Josephson arrays in series biased by a pulse drive based on opto-electronics, in order to increase the output voltage.
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  • Kooij, J. J. S., et al. (författare)
  • Updated European Consensus Statement on diagnosis and treatment of adult ADHD
  • 2019
  • Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 56, s. 14-34
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAttention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.MethodsThe European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.ResultsBesides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?ConclusionsADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
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  • Lehtonen, S., et al. (författare)
  • Environmentally driven extinction and opportunistic origination explain fern diversification patterns
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Combining palaeontological and neontological data offers a unique opportunity to investigate the relative roles of biotic and abiotic controls of species diversification, and the importance of origination versus extinction in driving evolutionary dynamics. Ferns comprise a major terrestrial plant radiation with an extensive evolutionary history providing a wealth of modern and fossil data for modelling environmental drivers of diversification. Here we develop a novel Bayesian model to simultaneously estimate correlations between diversification dynamics and multiple environmental trajectories. We estimate the impact of different factors on fern diversification over the past 400 million years by analysing a comprehensive dataset of fossil occurrences and complement these findings by analysing a large molecular phylogeny. We show that origination and extinction rates are governed by fundamentally different processes: originations depend on within-group diversity but are largely unaffected by environmental changes, whereas extinctions are strongly affected by external factors such as climate and geology. Our results indicate that the prime driver of fern diversity dynamics is environmentally driven extinction, with origination being an opportunistic response to diminishing ecospace occupancy.
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  • Lehtonen, T, et al. (författare)
  • SLEEP PROBLEMS IN EARLY RHEUMATOID ARTHRITIS
  • 2020
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 614-614
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • It is well known that patients with established RA suffer from problems with sleep quality[1]. There are however few, if any, studies on sleep quality among newly diagnosed patients.Objectives:To investigate the sleep quality among patients newly diagnosed with RA.Methods:We used the Swedish study Epidemiological Investigation of RA (EIRA) including patients at the time of diagnosis, based on the 1987 ACR criteria during 2008-2016. At 1 and 3 years after diagnosis, the patients were sent a questionnaire in which they were asked to rate their sleep quality on 10 different questions. We then calculated 6 different sleep components consisting of insomnia, non-restorative sleep, sleep problems, general quality of sleep, if poor sleep affected the health and if they were getting enough sleep[2].Sleep problems were defined as mostly or always having problems with either of the following: falling asleep, many awakenings with difficulties to go back to sleep, waking up early or having disturbed/restless sleep. Insomnia was defined as answering mostly or always on either problem with falling asleep, many awakenings with difficulties to go back to sleep or waking up early, in combination with mostly or always being tired during the day.Having problems with non-restorative sleep was defined as mostly or always having trouble waking up or not feeling well rested when waking up. We defined having problem with not getting enough sleep, sleep quality affecting the health and poor sleep quality as reporting any of the two highest scores on the corresponding questions.We then calculated the proportion of people experiencing no problems at 1 or 3 years after RA diagnosis, developing problems, improving or always having problems with their sleep.Results:We identified 1483 patients with data at either one or both time points. The mean age was 59 years (IQR 19), and 1063 (72%) were women. At 1 year, 36% of the patients reported having at least one type of sleep problem, after 3 years, this figure was 29%. Over 20% of the patients reported having “Rather big” or “Very big” problems with sleep after one year (Table 1) and 31% had problems at one or both time points (Table 2). Disturbed sleep was a problem for their health in 20% of the patients and 11% reported having “poor” or “very poor” sleep quality at both times. Insomnia was experienced by 118 (10%) patients at 1 year and 112 (11%) at 3 years.Table 1.Sleep problems at 1 and 3 years after diagnosis of RA.1 year3 yearsInsomnia118 (9%)112 (11%)Not getting enough sleep102 (8%)113 (11%)Problems with sleep in general270 (22%)231 (22%)Sleep quality affecting health238 (19%)197 (19%)Poor sleep quality218 (17%)209 (20%)Problem with non-restorative sleep218 (17%)154 (14%)Table 2.Individuals experiencing no problems, developing problems, improving or always having problems with their sleep at 1 and 3 years after diagnosis of RA.No problems at any time pointImprovedDeveloped problemsProblems at both 1 and 3 yearsInsomnia702 (85%)43 (5%)46 (6%)39 (5%)Not getting enough sleep719 (86%)36 (4%)47 (6%)34 (4%)Problems with sleep in general576 (69%)81 (10%)78 (9%)103 (12%)Sleep quality affecting health616 (74%)65 (8%)70 (8%)85 (10%)Poor sleep quality623 (74%)57 (7%)66 (8%)91 (11%)Problem with non-restorative sleep654 (78%)71 (8%)46 (5%)67 (8%)Conclusion:In a population-based early RA cohort receiving today’s standard care, 30% of the patients reported some type of sleep problem during the first 3 years. Although this is a lower rate than has been reported in established RA, this is a significant proportion of RA patients, and these findings warrant further studies to closer identify the course of sleep problems and the factors influencing it such as pain.References:[1]Bourguignon C et al PMID 14596374[2]Akerstedt T et al PMID 18484368Acknowledgments:The authors wish to acknowledge the EIRA study group and the EIRA data collectors.Disclosure of Interests:Tiina Lehtonen: None declared, Torbjörn Åkerstedr: None declared, Lauren Lyne: None declared, Lars Klareskog: None declared, Saedis Saevarsdottir Employee of: Part-time at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project, Lars Alfredsson: None declared, Helga Westerlind: None declared
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  • Lyne, L, et al. (författare)
  • Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study
  • 2022
  • Ingår i: RMD open. - : BMJ. - 2056-5933. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Most studies of rheumatoid arthritis (RA) and sleep have focused on established RA. We here investigate sleep quality and sleep duration in patients with newly diagnosed RA and during 1–12 years after diagnosis.MethodsData were collected on sleep 1–12 years after diagnosis from patients diagnosed 1998–2018 in the Swedish study Epidemiological Investigation of RA. Six sleep domains (sleep problems, non-restorative sleep, insomnia, insufficient sleep, sleep quality perceived as poor and sleep considered a health problem); a global sleep score and time spent in bed were estimated. Using logistic regression, ORs were calculated for each sleep outcome by disease duration. We explored whether pain (low (Visual Analogue Scale=0–20 mm, reference), intermediate=21–70, high=71–100) or functional impairment (Health Assessment Questionnaire>1.0) was associated with problems.ResultsWe had sleep data on 4131 observations (n=3265 individuals). Problems with ≥1 sleep domain (global sleep score) was reported in 1578 observations (38%) and increased with disease duration (OR 1.04, 95% CI 1.02 to 1.07). Median time in bed was 8 hours (Q1-Q3: 7.5–9.0). High-grade pain increased the likelihood of sleep problems ~3–9 fold, and increased functional impairment ~4–8 fold.ConclusionIn this cohort of newly diagnosed patients with RA with access to the current treatment from diagnosis, we did not find any major problems with sleep, and existing sleep problems related mainly to pain and reduced function. Treatment of sleep problems in RA should be guided towards treating the underlying problem causing the sleep disturbance.
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