1. |
- Hilbert, Kevin, et al.
(författare)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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Ingår i: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
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Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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3. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Tidskriftsartikel (refereegranskat)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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4. |
- Schunkert, Heribert, et al.
(författare)
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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
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Tidskriftsartikel (refereegranskat)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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5. |
- Ahmed, Aisha S., et al.
(författare)
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Attenuation of Pain and Inflammation in Adjuvant-Induced Arthritis by the Proteasome Inhibitor MG132
- 2010
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:7, s. 2160-2169
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In rheumatoid arthritis (RA), pain and joint destruction are initiated and propagated by the production of proinflammatory mediators. Synthesis of these mediators is regulated by the transcription factor NF-kappa B, which is controlled by the ubiquitin proteasome system (UPS). The present study explored the effects of the proteasome inhibitor MG132 on inflammation, pain, joint destruction, and expression of sensory neuropeptides as markers of neuronal response in a rat model of arthritis. Methods. Arthritis was induced in rats by injection of heat-killed Mycobacterium butyricum. Arthritis severity was scored, and nociception was evaluated by mechanical pressure applied to the hind paw. Joint destruction was assessed by radiologic and histologic analyses. NF-kappa B DNA-binding activity was analyzed by electromobility shift assay, and changes in the expression of the p50 NF-kappa B subunit and the proinflammatory neuropeptides substance P (SP) and calcitonin generelated peptide (CGRP) were detected by immunohistochemistry. Results. Arthritic rats treated with MG132 demonstrated a marked reduction in inflammation, pain, and joint destruction. The elevated DNA-binding activity of the NF-kappa B/p50 homodimer and p50, as well as the neuronal expression of SP and CGRP, observed in the ankle joints of arthritic rats were normalized after treatment with MG132. Conclusion. In arthritic rats, inhibition of proteasome reduced the severity of arthritis and reversed the pain behavior associated with joint inflammation. These effects may be mediated through the inhibition of NF-kappa B activation and may possibly involve the peripheral nervous system. New generations of nontoxic proteasome inhibitors may represent a novel pharmacotherapy for RA.
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6. |
- Ahmed, Aisha Siddiqah, et al.
(author)
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Proteasome inhibitor MG132 modulates inflammatory pain by central mechanisms in adjuvant arthritis.
- 2017
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In: International journal of rheumatic diseases. - 1756-185X. ; 20:1, s. 25-32
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Journal article (peer-reviewed)abstract
- AIMS: In rheumatoid arthritis (RA), pain and inflammation are initial symptoms followed by various degrees of bone and cartilage destruction. Previously, we have shown that reversible proteasome inhibitor MG132 attenuates pain and joint inflammation in a rat model of adjuvant-arthritis. Our present study aims to study the effects of MG132 on molecular changes in the dorsal root ganglia (DRG) and in the spinal cord (SC) using the same animal model.METHODS: Arthritis was induced by heat-killed Mycobacterium butyricum in rats. The expression of substance P (SP) was analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in DRG and in the SC. The nuclear factor-κB (NF-κB) DNA-binding activity in the SC was analyzed by electromobility shift assay.RESULTS: Arthritic rats treated daily with MG132 demonstrated a marked reduction of SP gene expression in the DRG and number of SP-positive cells was reduced. In the spinal cord of arthritic rats elevated SP messenger RNA levels were normalized and NF-κB-DNA-binding activity was down-regulated in arthritic rats treated with MG132.CONCLUSION: Our results indicate that proteasome inhibitor MG132 attenuates pain in adjuvant arthritis by targeting the sensory neuropeptide substance P in the peripheral and central nervous systems. These effects may be mediated through the inhibition of NF-κB activation.
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7. |
- Ahmed, Aisha S, et al.
(author)
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Suppression of pain and joint destruction by inhibition of the proteasome system in experimental osteoarthritis
- 2012
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 153:1, s. 18-26
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Journal article (peer-reviewed)abstract
- Osteoarthritis is a degenerative joint disease with pain and loss of joint function as major pathological features. Recent studies show that proteasome inhibitors reduce pain in various pathological conditions. We evaluated the effects of MG132, a reversible proteasome inhibitor on pain and joint destruction in a rat model of osteoarthritis. Osteoarthritis was induced by intraarticular injection of monosodium iodoacetate into the rat knee. Knee joint stiffness was scored and nociception was evaluated by mechanical pressure applied to the respective hind paw. Knee joint destruction was assessed by radiological and histological analyses. Expression of matrix metalloproteinase-3 (MMP-3) was analyzed by quantitative reverse transcription polymerase chain reaction in the knee articular cartilage. Expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was studied in the dorsal root ganglia (L4–L6) by quantitative reverse transcription polymerase chain reaction and in the knee joints by immunohistochemistry. Our results indicate that daily treatment of osteoarthritic rats with MG132 significantly increases their mobility while the swelling, pain thresholds, and pathological features of the affected joints were reduced. Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the arthritic rats was normalized by MG132 administration. We conclude that the proteasome inhibitor MG132 reduces pain and joint destruction, probably by involving the peripheral nervous system, and that changes in SP and CGRP expression correlate with alterations in behavioural responses. Our findings suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy for osteoarthritis.
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8. |
- Andersson, Martin K, et al.
(author)
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Effects on osteoclast and osteoblast activities in cultured mouse calvarial bones by synovial fluids from patients with a loose joint prosthesis and from osteoarthritis patients.
- 2007
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In: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 9:1
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Journal article (peer-reviewed)abstract
- Aseptic loosening of a joint prosthesis is associated with remodelling of bone tissue in the vicinity of the prosthesis. In the present study, we investigated the effects of synovial fluid (SF) from patients with a loose prosthetic component and periprosthetic osteolysis on osteoclast and osteoblast activities in vitro and made comparisons with the effects of SF from patients with osteoarthritis (OA). Bone resorption was assessed by the release of calcium 45 (45Ca) from cultured calvariae. The mRNA expression in calvarial bones of molecules known to be involved in osteoclast and osteoblast differentiation was assessed using semi-quantitative reverse transcription-polymerase chain reaction (PCR) and real-time PCR. SFs from patients with a loose joint prosthesis and patients with OA, but not SFs from healthy subjects, significantly enhanced 45Ca release, effects associated with increased mRNA expression of calcitonin receptor and tartrate-resistant acid phosphatase. The mRNA expression of receptor activator of nuclear factor-kappa-B ligand (rankl) and osteoprotegerin (opg) was enhanced by SFs from both patient categories. The mRNA expressions of nfat2 (nuclear factor of activated T cells 2) and oscar (osteoclast-associated receptor) were enhanced only by SFs from patients with OA, whereas the mRNA expressions of dap12 (DNAX-activating protein 12) and fcrgamma (Fc receptor common gamma subunit) were not affected by either of the two SF types. Bone resorption induced by SFs was inhibited by addition of OPG. Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity. The mRNA expression of alkaline phosphatase and osteocalcin was increased by SFs from patients with OA, whereas only osteocalcin mRNA was increased by SFs from patients with a loose prosthesis. Our findings demonstrate the presence of a factor (or factors) stimulating both osteoclast and osteoblast activities in SFs from patients with a loose joint prosthesis and periprosthetic osteolysis as well as in SFs from patients with OA. SF-induced bone resorption was dependent on activation of the RANKL/RANK/OPG pathway. The bone-resorbing activity could not be attributed solely to any of the known pro-inflammatory cytokines, well known to stimulate bone resorption, or to RANKL or prostaglandin E2 in SFs. The data indicate that SFs from patients with a loose prosthesis or with OA stimulate bone resorption and that SFs from patients with OA are more prone to enhance bone formation.
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9. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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10. |
- Brodén, Cyrus, et al.
(author)
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High risk of early periprosthetic fractures after primary hip arthroplasty in elderly patients using a cemented, tapered, polished stem : an observational, prospective cohort study on 1,403 hips with 47 fractures after mean follow-up time of 4 years
- 2015
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 86:2, s. 169-174
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Journal article (peer-reviewed)abstract
- Background and purpose - Postoperative periprosthetic femoral fracture (PPF) after hip arthroplasty is associated with considerable morbidity and mortality. We assessed the incidence and characteristics of periprosthetic fractures in a consecutive cohort of elderly patients treated with a cemented, collarless, polished and tapered femoral stem (CPT). Patients and methods - In this single-center prospective cohort study, we included 1,403 hips in 1,357 patients (mean age 82 (range 52-102) years, 72% women) with primary osteoarthritis (OA) or a femoral neck fracture (FNF) as indication for surgery (367 hips and 1,036 hips, respectively). 64% of patients were ASA class 3 or 4. Hip-related complications and need for repeat surgery were assessed at a mean follow-up time of 4 (1-7) years. A Cox regression analysis was used to evaluate risk factors associated with PPF. Results - 47 hips (3.3%) sustained a periprosthetic fracture at median 7 (2-79) months postoperatively; 41 were comminute Vancouver B2 or complex C-type fractures. The fracture rate was 3.8% for FNF patients and 2.2% for OA patients (hazard ratio (HR) = 4; 95% CI: 1.3-12). Patients > 80 years of age also had a higher risk of fracture (HR = 2; 95% CI: 1.1-4.5). Interpretation - We found a high incidence of early PPF associated with the CPT stem in this old and frail patient group. A possible explanation may be that the polished tapered stem acts as a wedge, splitting the femur after a direct hip contusion. Our results should be confirmed in larger, registry-based studies, but we advise caution when using this stem for this particular patient group.
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11. |
- Calabrese, Claudia, et al.
(author)
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Genomic basis for RNA alterations in cancer
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
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Journal article (peer-reviewed)abstract
- Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
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12. |
- Chammout, Ghazi, et al.
(author)
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HOPE-Trial: Hemiarthroplasty Compared with Total Hip Arthroplasty for Displaced Femoral Neck Fractures in Octogenarians : A Randomized Controlled Trial
- 2019
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In: JB & JS open access. - : The Journal of Bone and Joint Surgery. - 2472-7245. ; 4:2
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Journal article (peer-reviewed)abstract
- Background: The choice of primary hemiarthroplasty or total hip arthroplasty in patients ≥80 years of age with a displaced femoral neck fracture has not been adequately studied. As the number of healthy, elderly patients ≥80 years of ageis continually increasing, optimizing treatments for improving outcomes and reducing the need for secondary surgery is an important consideration. The aim of the present study was to compare the results of hemiarthroplasty with those of totalhip arthroplasty in patients ≥80 years of age.Methods: This prospective, randomized, single-blinded trial included 120 patients with a mean age of 86 years (range, 80 to 94 years) who had sustained an acute displaced femoral neck fracture <36 hours previously. The patients were randomized to treatment with hemiarthroplasty (n = 60) or total hip arthroplasty (n = 60). The primary end points were hip function and health-related quality of life at 2 years. Secondary end points included hip-related complications and reoperations, mortality, pain in the involved hip, activities of daily living, surgical time, blood loss, and general complications.The patients were reviewed at 3 months and 1 and 2 years.Results: We found no differences between the groups in terms of hip function, health-related quality of life, hip-related complications and reoperations, activities of daily living, or pain in the involved hip. Hip function, activities of daily living,and pain in the involved hip deteriorated in both groups compared with pre-fracture values. The ability to regain previous walking function was similar in both groups.Conclusions: We found no difference in outcomes after treatment with either hemiarthroplasty or total hip arthroplasty inactive octogenarians and nonagenarians with a displaced femoral neck fracture up to 2 years after surgery. Hemiarthroplastyis a suitable procedure in the short term for this group of patients.Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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13. |
- Chammout, Ghazi Khalil, et al.
(author)
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Total hip replacement versus open reduction and internal fixation of displaced femoral neck fractures : a randomized long-term follow-up study
- 2012
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In: Journal of Bone and Joint Surgery. American volume. - : Journal of Bone and Joint Surgery. - 0021-9355 .- 1535-1386. ; 94:21, s. 1921-1928
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Journal article (peer-reviewed)abstract
- Background: Clinical trials with short and intermediate-term follow-up have demonstrated superior results for total hip replacement as compared with internal fixation with regard to hip function and the need for secondary surgery in elderly patients with a displaced intracapsular femoral neck fracture. The aim of the present study was to compare the results of total hip replacement with those of internal fixation over a long-term follow-up period of seventeen years.Methods: We enrolled 100 patients who had sustained a femoral neck fracture in a single-center, randomized controlled trial; all patients had had a healthy hip before the injury. The study group included seventy-nine women and twenty-one men with a mean age of seventy-eight years (range, sixty-five to ninety years). The subjects were randomly assigned to either total hip replacement (the arthroplasty group) (n = 43) or internal fixation (the control group) (n = 57). The primary end point was hip function, evaluated with use of the Harris hip score. Secondary end points included mortality, reoperations, gait speed, and activities of daily life. Follow-up evaluations were performed at threemonths and at one, two, four, eleven, and seventeen years.Results: The Harris hip score was higher in the total hip arthroplasty group, with a mean difference of 14.7 points (95% confidence interval, 9.2 to 20.1 points; p < 0.001 [analysis of covariance]) during the study period. We found no difference in mortality between the two groups. Four patients (9%) in the total hip replacement group and twenty-two patients (39%) in the internal fixation group had undergone a major reoperation (relative risk, 0.24; 95% confidence interval, 0.09 to 0.64). The overall reoperation rate was 23% (ten of forty-three) in the total hip replacement group and 53% (thirty of fifty-seven) in the internal fixation group (relative risk, 0.44; 95% confidence interval, 0.24 to 0.80). The results related to gait speed and activities of daily living favored the arthroplasty group during the first year.Conclusions: Over a period of seventeen years in a group of healthy, elderly patients with a displaced femoral neck fracture, total hip replacement provided better hip function and significantly fewer reoperations compared with internal fixation without increasing mortality.
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14. |
- Chammout, Ghazi, et al.
(author)
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Primary hemiarthroplasty for the elderly patient with cognitive dysfunction and a displaced femoral neck fracture : a prospective, observational cohort study
- 2021
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In: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 33:5, s. 1275-1283
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Journal article (peer-reviewed)abstract
- Background: At least one-third of hip fracture patients have some degree of impaired cognitive status, which may complicate their postoperative rehabilitation.Aim: We aimed to describe the outcome for elderly patients with cognitive dysfunction operated with hemiarthroplasty (HA) for a femoral neck fracture and to study the impact postoperative geriatric rehabilitation has on functional outcome up to 1 year after surgery.Methods: 98 patients with a displaced femoral neck fracture with a mean age of 86 years were included and followed up to 1 year. The outcomes were hip-related complications and reoperations, the capacity to return to previous walking ability, health-related quality of life, hip function and mortality.Results: The prevalence of hip complications leading to a major reoperation was 6% and the 1-year mortality rate was 31%. The lack of geriatric rehabilitation was correlated with poorer outcomes overall and those who receive geriatric rehabilitation were less likely to be confined to a wheelchair or bedridden at the 1-year follow-up.Conclusions: Hemiarthroplasty is an acceptable option for elderly patients with a displaced femoral neck fracture and cognitive dysfunction. A lack of structured rehabilitation is associated with a significant deterioration in walking ability despite a well-functioning hip. However, the causality of this could be due to selection bias of healthier patients being sent to geriatric rehabilitation.
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15. |
- Dahlstrand, Henrik, et al.
(author)
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Comparison of metal ion concentrations and implant survival after total hip arthroplasty with metal-on-metal versus metal-on-polyethylene articulations : a 16-year follow-up of a prospective randomized study
- 2017
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:5, s. 490-495
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Journal article (peer-reviewed)abstract
- Background and purpose - Large metal-on-metal (MoM) articulations are associated with metal wear and corrosion, leading to increased metal ion concentrations and unacceptable revision rates. There are few comparative studies of 28-mm MoM articulations with conventional metal-on-polyethylene (MoP) couplings. We present a long-term follow-up of a randomized controlled trial comparing MoM versus MoP 28-mm articulations, focused on metal ions and implant survival. Patients and methods - 85 patients with a mean age of 65 years at surgery were randomized to a MoM (Metasul) or a MoP (Protasul) bearing. After 16 years, 38 patients had died and 4 had undergone revision surgery. 13 patients were unavailable for clinical follow-up, leaving 30 patients (n = 14 MoM and n = 16 MoP) for analysis of metal ion concentrations and clinical outcome. Results - 15-year implant survival was similar in both groups (MoM 96% [95% CI 88-100] versus MoP 97% [95% CI 91-100]). The mean serum cobalt concentration was 4-fold higher in the MoM (1.5 mu g/L) compared with the MoP cohort (0.4 mu g/L, p < 0.001) and the mean chromium concentration was double in the MoM (2.2 mu g/L) compared with the MoP cohort (1.0 mu g/L, p = 0.05). Mean creatinine levels were similar in both groups (MoM 93 mu mol/L versus MoP 92 mu mol/L). Harris hip scores differed only marginally between the MoM and MoP cohorts. Interpretation - This is the longest follow-up of a randomized trial on 28-mm MoM articulations, and although implant survival in the 2 groups was similar, metal ion concentrations remained elevated in the MoM cohort even in the long term.
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16. |
- Dahlstrand, Henrik, et al.
(author)
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Elevated serum concentrations of cobalt, chromium, nickel, and manganese after metal-on-metal alloarthroplasty of the hip : a prospective randomized study
- 2009
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In: The Journal of Arthroplasty. - : Elsevier BV. - 0883-5403 .- 1532-8406. ; 24:6, s. 837-845
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Journal article (peer-reviewed)abstract
- In this prospective randomized study, we investigate metal ion concentrations and clinical outcome 2 years after metal-on-metal (28 patients) or metal-on-polyethylene (26 patients) hip arthroplasty with 28-mm modular heads. Metal ion concentrations in patient serum were analyzed by high-resolution plasma mass spectrometry. The clinical outcome was almost identical in both groups with respect to the Harris hip score and the Medical Outcome Study Short Form-36; and on plain radiography, no signs of loosening occurred in any group. In the metal-on-metal group, concentrations of all investigated ions increased significantly when compared with preoperative values: cobalt, 15.3-fold (95% confidence interval [CI], 9.4-21.2); chromium, 5.2-fold (CI, 3.5-7.0); nickel, 2.1-fold (CI, 1.2-3.0); and manganese, 1.6-fold (CI, 1.3-2.0). In the metal-on-polyethylene group, a smaller but significant increase in the concentrations of cobalt and nickel occurred, whereas concentrations of the other ions did not change significantly.
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17. |
- Einhauser, Sebastian, et al.
(author)
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Time Trend in SARS-CoV-2 Seropositivity, Surveillance Detection- and Infection Fatality Ratio until Spring 2021 in the Tirschenreuth County-Results from a Population-Based Longitudinal Study in Germany
- 2022
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In: Viruses. - : MDPI AG. - 1999-4915. ; 14:6
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Journal article (peer-reviewed)abstract
- Herein, we provide results from a prospective population-based longitudinal follow-up (FU) SARS-CoV-2 serosurveillance study in Tirschenreuth, the county which was hit hardest in Germany in spring 2020 and early 2021. Of 4203 individuals aged 14 years or older enrolled at baseline (BL, June 2020), 3546 participated at FU1 (November 2020) and 3391 at FU2 (April 2021). Key metrics comprising standardized seroprevalence, surveillance detection ratio (SDR), infection fatality ratio (IFR) and success of the vaccination campaign were derived using the Roche N- and S-Elecsys anti-SARS-CoV-2 test together with a self-administered questionnaire. N-seropositivity at BL was 9.2% (1st wave). While we observed a low new seropositivity between BL and FU1 (0.9%), the combined 2nd and 3rd wave accounted for 6.1% new N-seropositives between FU1 and FU2 (ever seropositives at FU2: 15.4%). The SDR decreased from 5.4 (BL) to 1.1 (FU2) highlighting the success of massively increased testing in the population. The IFR based on a combination of serology and registration data resulted in 3.3% between November 2020 and April 2021 compared to 2.3% until June 2020. Although IFRs were consistently higher at FU2 compared to BL across age-groups, highest among individuals aged 70+ (18.3% versus 10.7%, respectively), observed differences were within statistical uncertainty bounds. While municipalities with senior care homes showed a higher IFR at BL (3.0% with senior care home vs. 0.7% w/o), this effect diminished at FU2 (3.4% vs. 2.9%). In April 2021 (FU2), vaccination rate in the elderly was high (>77.4%, age-group 80+).
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18. |
- Gordon, Max, et al.
(author)
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Age- and health-related quality of life after total hip replacement.
- 2014
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In: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 85:3, s. 244-249
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Journal article (peer-reviewed)abstract
- Background - While age is a common confounder, its impact on health-related quality of life (HRQoL) after total hip replacement is uncertain. This could be due to improper statistical modeling of age in previous studies, such as treating age as a linear variable or by using age categories. We hypothesized that there is a non-linear association between age and HRQoL. Methods - We selected a nationwide cohort from the Swedish Hip Arthroplasty Register of patients operated with total hip replacements due to primary osteoarthritis between 2008 and 2010. For estimating HRQoL, we used the generic health outcome questionnaire EQ-5D of the EuroQol group that consits or 2 parts: the EQ-5D index and the EQ VAS estimates. Using linear regression, we modeled the EQ-5D index and the EQ VAS against age 1 year after surgery. Instead of using a straight line for age, we applied a method called restricted cubic splines that allows the line to bend in a controlled manner. Confounding was controlled by adjusting for preoperative HRQoL, sex, previous contralateral hip surgery, pain, and Charnley classification. Results - Complete data on 27,245 patients were available for analysis. Both the EQ-5D index and EQ VAS showed a non-linear relationship with age. They were fairly unaffected by age until the patients were in their late sixties, after which age had a negative effect. Interpretation - There is a non-linear relationship between age and HRQoL, with improvement decreasing in the elderly.
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19. |
- Gordon, Max, et al.
(author)
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Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty: A Nationwide Cohort Study.
- 2016
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In: Medicine. - 1536-5964 .- 0025-7974. ; 95:6
-
Journal article (peer-reviewed)abstract
- Total hip arthroplasty is a common and important treatment for osteoarthritis patients. Long-term cardiovascular effects elicited by osteoarthritis or the implant itself remain unknown. The purpose of the present study was to determine if there is an increased risk of late cardiovascular mortality and morbidity after total hip arthroplasty surgery.A nationwide matched cohort study with data on 91,527 osteoarthritis patients operated on, obtained from the Swedish Hip Arthroplasty Register. A control cohort (n=270,688) from the general Swedish population was matched 1:3 to each case by sex, age, and residence. Mean follow-up time was 10 years (range, 7-21).The exposure was presence of a hip replacement for more than 5 years. The primary outcome was cardiovascular mortality after 5 years. Secondary outcomes were total mortality and re-admissions due to cardiovascular events.During the first 5 to 9 years, the arthroplasty cohort had a lower cardiovascular mortality risk compared with the control cohort. However, the risk in the arthroplasty cohort increased over time and was higher than in controls after 8.8 years (95% confidence interval [CI] 7.0-10.5). Between 9 and 13 years postoperatively, the hazard ratio was 1.11 (95% CI 1.05-1.17). Arthroplasty patients were also more frequently admitted to hospital for cardiovascular reasons compared with controls, with a rate ratio of 1.08 (95% CI 1.06-1.11).Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation when compared with controls.
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20. |
- Gorski, Mathias, et al.
(author)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
-
Journal article (peer-reviewed)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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21. |
- Grondal, Lollo, et al.
(author)
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The foot : still the most important reason for walking incapacity in rheumatoid arthritis - Distribution of symptomatic joints in 1,000 RA patients
- 2008
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In: Acta Orthopaedica. - New York, USA : Informa Healthcare. - 1745-3674 .- 1745-3682. ; 79:2, s. 257-261
-
Journal article (peer-reviewed)abstract
- Background and purpose: Our knowledge of frequency of foot involvement in rheumatoid arthritis (RA) is still often based on a study from Finland in 1956. Great changes in the treatment of RA may have led to a different situation. We investigated the distribution of joint involvement in RA patients today, with special attention given to the feet and subjective walking ability.Methods: 1,000 RA patients answered a questionnaire concerning joints affected, joint surgery, foot problems, and subjectively experienced reasons for walking incapacity.Results: In 45% of the patients, the forefoot was involved at the start of the disease. In 17%, the hindfoot/ankle was involved at the start. Only hand symptoms were commoner. 80% of patients reported current foot problems, 86% in the forefoot and 52% in the hindfoot/ankle. Difficulty in walking due to the feet was reported by 71%. For 41% of patients, the foot was the most important part of the lower extremity causing reduced walking capacity, and for 32% it was the only part.Interpretation: After the hand, the foot was the most frequently symptomatic joint complex at the start of the disease, but also during active medical treatment. The foot caused walking disability in three-quarters of the cases and-4 times as often as the knee or the hip-it was the only joint to subjectively impair gait.
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22. |
- Hailer, Nils P., et al.
(author)
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Dual-mobility cups for revision due to instability are associated with a low rate of re-revisions due to dislocation.
- 2012
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In: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 83:6, s. 566-571
-
Journal article (peer-reviewed)abstract
- Background and purpose Revision total hip arthroplasty (THA) due to recurrent dislocations is associated with a high risk of persistent instability. We hypothesized that the use of dual-mobility cups would reduce the risk of re-revision due to dislocation after revision THA. Patients and methods 228 THA cup revisions (in 228 patients) performed due to recurrent dislocations and employing a specific dual-mobility cup (Avantage) were identified in the Swedish Hip Arthroplasty Register. Kaplan-Meier survival analysis was performed with re-revision due to dislocation as the primary endpoint and re-revision for any reason as the secondary endpoint. Cox regression models were fitted in order to calculate the influence of various covariates on the risk of re-revision. Results 58 patients (25%) had been revised at least once prior to the index cup revision. The surgical approach at the index cup revision was lateral in 99 cases (44%) and posterior in 124 cases (56%). Median follow-up was 2 (0-6) years after the index cup revision, and by then 18 patients (8%) had been re-revised for any reason. Of these, 4 patients (2%) had been re-revised due to dislocation. Survival after 2 years with the endpoint revision of any component due to dislocation was 99% (95% CI: 97-100), and it was 93% (CI: 90-97) with the endpoint revision of any component for any reason. Risk factors for subsequent re-revision for any reason were age between 50-59 years at the time of the index cup revision (risk ratio (RR) = 5 when compared with age > 75, CI: 1-23) and previous revision surgery to the relevant joint (RR = 1.7 per previous revision, CI: 1-3). Interpretation The risk of re-revision due to dislocation after insertion of dual-mobility cups during revision THA performed for recurrent dislocations appears to be low in the short term. Since most dislocations occur early after revision THA, we believe that this device adequately addresses the problem of recurrent instability. Younger age and prior hip revision surgery are risk factors for further revision surgery. However, problems such as potentially increased liner wear and subsequent aseptic loosening may be associated with the use of such devices in the long term.
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23. |
- Hailer, Nils P., et al.
(author)
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Elevation of circulating HLA DR+ CD8+ T-cells and correlation with chromium and cobalt concentrations 6 years after metal-on-metal hip arthroplasty : a randomized trial
- 2011
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 82:1, s. 6-12
-
Journal article (peer-reviewed)abstract
- Background and purpose Following metal-on-metal hip arthroplasty (THA), immunological reactions including changes in lymphocyte populations, aseptic loosening, and lymphocytic pseudotumors occur. We hypothesized that changes in lymphocyte subpopulations would be associated with elevated metal ion concentrations. Methods A randomized trial involving 85 patients matched for age and sex and randomized to receiving metal-on-metal (n = 41) or metal-on-polyethylene total hip arthroplasty (n = 44) was conducted. 36 patients were eligible for follow-up after mean 7 (6-8) years. Concentrations of chromium and cobalt were analyzed by high-resolution inductively coupled plasma mass spectrometry. Leukocyte subpopulations and immunoglobulins in patient blood were measured using standard laboratory methods. Results Patients with a metal-on-metal hip had higher serum concentrations of chromium (1.05 vs. 0.36 μg/L; p < 0.001) and cobalt (0.86 vs. 0.24 μg/L; p < 0.001) than those with metal-on-polyethylene. The percentage of HLA DR(+) CD8(+) T-cells was higher in the metal-on-metal group (10.6 vs. 6.7%; p = 0.03) and correlated positively with chromium and cobalt concentrations in patient blood (Pearson's correlation coefficient: 0.39, p = 0.02; 0.36, p = 0.03, respectively). The percentage of B-cells was lower in the metal-on-metal group (p = 0.01). The two groups were similar with respect to immunoglobulin concentrations and Harris hip scores, and there were no radiographic signs of loosening. Interpretation We conclude that immunological alterations appear to be associated with increased cobalt and chromium concentrations. It is tempting to speculate that HLA DR(+) CD8(+) T-cells are involved in the pathogenesis of allergic reactions, implant loosening, and lymphocytic pseudotumors.
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24. |
- Heid, Iris M, et al.
(author)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Journal article (peer-reviewed)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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25. |
- Jedenmalm, Anneli, et al.
(author)
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A new approach for assessment of wear in metal-backed acetabular cups using computed tomography : a phantom study with retrievals
- 2008
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 79:2, s. 218-224
-
Journal article (peer-reviewed)abstract
- Background and purpose Polyethylene wear is an important cause of aseptic loosening in hip arthroplasty. Detection of significant wear usually happens late on, since available diagnostic techniques are either not sensitive enough or too complicated and expensive for routine use. This study evaluates a new approach for measurement of linear wear of metal-backed acetabular cups using CT as the intended clinically feasible method. Material and methods 8 retrieved uncemented metal-backed acetabular cups were scanned twice ex vivo using CT. The linear penetration depth of the femoral head into the cup was measured in the CT volumes using dedicated software. Landmark points were placed on the CT images of cup and head, and also on a reference plane in order to calculate the wear vector magnitude and angle to one of the axes. A coordinate-measuring machine was used to test the accuracy of the proposed CT method. For this purpose, the head diameters were also measured by both methods. Results Accuracy of the CT method for linear wear measurements was 0.6 nm and wear vector angle was 27 degrees. No systematic difference was found between CT scans. Interpretation This study on explanted acetabular cups shows that CT is capable of reliable measurement of linear wear in acetabular cups at a clinically relevant level of accuracy. It was also possible to use the method for assessment of direction of wear.
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26. |
- Jedenmalm, Anneli, 1977-
(author)
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Computed Tomography of Acetabular Cup Wear and Effect of Surface Roughness on Wear and Oxidation of UHMWPE Hip Prostheses
- 2007
-
Doctoral thesis (other academic/artistic)abstract
- Aseptic loosening is the most common complication in total hip replacement (5- 10% at 10 years follow up). The magnitude of the problem is illustrated by the fact that about one million hip prostheses are implanted worldwide each year. Many parameters affect the longevity of the implant where aseptic loosening caused by wear debris and raised intraarticular pressure are the most common reasons for revisions. To monitor wear in vivo and also to predict the longevity of new materials for hip prostheses are therefore important issues. The main aims of this thesis are to validate a new non-invasive method for assessment of in vivo wear of acetabular cups in 3 dimensions using computed tomography (CT), and to investigate the influence of counterface surface roughness and γ-irradiation sterilisation in wear testing of ultra high molecular weight polyethylene (UHMWPE) for hip prostheses. A new low friction coating, Micronite was also investigated using a multidirectional pin-on-disk machine. The 3D-CT method was found to be easy to use and showed an accuracy and repeatability at a clinical relevant level for assessment of acetabular cup wear. The method should lend itself well to semi-automation. The Micronite coating showed potential for use in artificial joints due to its low friction and intact surface after wear testing compared to a stainless steel disk that showed wear tracks. However, the surface roughness of the stainless steel disks was increased by the coating. Therefore further investigations are needed. In the hip simulator study, it was found that a rougher counter surface increased the wear 2-fold. It was also found that sterilisation by γ-irradiation (in nitrogen) increased both fluid absorption and wear of the UHMWPE cups compared to the non-sterilised cups. A study with infrared spectroscopy and derivatisation techniques using NO, HCl, and SO2 showed that the increased wear and absorption were due to oxidation induced by γ-irradiation. The oxidation was found to be inhomogeneous with higher oxidation near the surfaces. The contribution of the roughened heads to the increased oxidation was only minor. Crystallinity changes upon wear testing of the sterilised cups were detected with Raman spectroscopy and differential scanning calorimetry. However, the changes were small and the influence on wear properties is therefore questionable.
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27. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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28. |
- Kelly-Pettersson, Paula, et al.
(author)
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The influence of depression on patient-reported outcomes for hip-fracture patients 1 year after surgery : a prospective cohort study.
- 2020
-
In: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:2, s. 247-255
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Depression is common in elderly hip-fracture patients and together with cognitive impairment is associated with increased risk of mortality.AIM: We aimed to examine the influence depression has on patient-reported outcome up to 1 year after acute hip fracture.METHODS: 162 hip-fracture patients participated in the prospective observational cohort study and were followed up at baseline, and 3 and 12 months using patient-reported outcome scores. Patients with cognitive impairment were excluded. Depression was defined as a score ≥ 8 on the depression subscale of the Hospital Anxiety Depression Scale (HADS D), having a diagnosis of depression or being treated with anti-depressant medication. Hip function was assessed using Harris Hip Score (HHS), EQ-5D was used to assess health status and Quality of life, and the Pain Numerical Rating Scale (PRNS) was used to assess pain levels. A linear regression model adjusted for group, age, sex, and ASA class was used to identify risk factors for functional outcome 12 months after fracture.RESULTS: 35 patients were included in the depression group versus 127 in the control group. No statistical differences were found in the demographic data (age, sex, ASA class, fracture type, operation method, living situation, activities of daily living ADL and clinical pathway) between the groups. In the regression model, we found no correlation between depression and the patient-reported outcome.CONCLUSION: In young elderly hip fracture patients without cognitive dysfunction, depression may not be of major importance for the rehabilitation of hip function in the short term.
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29. |
- Kelly-Pettersson, Paula, et al.
(author)
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Waiting time to surgery is correlated with an increased risk of serious adverse events during hospital stay in patients with hip-fracture : A cohort study.
- 2017
-
In: International Journal of Nursing Studies. - : Elsevier BV. - 0020-7489 .- 1873-491X. ; 69, s. 91-97
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Hip fractures are common in the elderly and are associated with a high adverse event and mortality rate. Time to surgery is one of the major modifiable risk factors influencing adverse outcomes in hip-fracture patients. National guidelines and recommendations have been introduced which advocate specific time frames in which surgery should be performed i.e. within 24-48h. These time constraints have been arbitrarily set without being modelled on the linear assumption i.e. that risk increases continually over time and not within specific cut-off times.OBJECTIVES: To investigate how waiting time to surgery influenced the risk of serious adverse events in hip-fracture patients during the hospital stay and to examine how the risk increased over time.DESIGN: An observational single cohort study Participants 576 patients (72.4% females, mean [SD] age 82 [10]) years, with a hip fracture were included in the cohort study.METHODS: The outcomes of the study were the occurrence of serious adverse events during hospital stay, length of stay and one-year mortality. A structured medical record review was carried out to identify outcomes and mortality data was obtained from the Swedish National Death Registry. Waiting time to surgery was used as the exposure variable and age, sex, type of fracture, comorbidities using the American Society of Anaesthesiologists classification score and the presence of cognitive dysfunction were identified as confounders. A logistic regression analysis was performed to identify risk factors influencing outcomes.RESULTS: A total of 119 patients (20.6%) suffered 397 (range 1-5) serious adverse events during hospital stay. Every 10h of waiting time to surgery increased the risk of serious adverse events by 12% (odds ratio 1.12 [95% confidence interval 1.02-1.23]). We found no optimal cut-off times for waiting time to surgery. For every 24h of waiting time, the length of stay from surgery was increased by 0.6days (95% CI 0.1-1.1). We found no correlation between waiting time to surgery and one-year mortality.CONCLUSIONS: A large proportion of patients suffered from at least one serious adverse event after hip-fracture surgery and there are no safe limits for waiting time to surgery for hip-fracture patients. As the risk increases with every hour of waiting time, patients with higher American Society of Anesthesiologists classification scores, males and those with subtrochanteric fractures should be prioritized for surgery.
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30. |
- Kim, Min Seo, et al.
(author)
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Global burden of peripheral artery disease and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2023
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In: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:10, s. E1553-E1565
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Journal article (peer-reviewed)abstract
- Background: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.Methods: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.Findings: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99 center dot 2-128 center dot 4), with a global prevalence of 1 center dot 52% (95% UI 1 center dot 33-1 center dot 72), of which 42 center dot 6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14 center dot 91% [12 center dot 41-17 center dot 87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69 center dot 4% (64 center dot 2-74 center dot 3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.Interpretation: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.
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31. |
- Lindberg, Johan, 1977-, et al.
(author)
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Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology
- 2006
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:2
-
Journal article (peer-reviewed)abstract
- In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative levels of intra-patient and inter-patient variation could be assessed. The biopsies were obtained from 13 different patients: 7 by orthopedic surgery and 6 by rheumatic arthroscopy. The data show that levels of heterogeneity varied substantially between the biopsies, because the number of genes found to be differentially expressed between pairs of biopsies from the same knee ranged from 6 to 2,133. Both arthroscopic and orthopedic biopsies were examined, allowing us to compare the two sampling methods. We found that the average number of differentially expressed genes between biopsies from the same patient was about three times larger in orthopedic than in arthroscopic biopsies. Using a parallel analysis of the tissues by immunohistochemistry, we also identified orthopedic biopsies that were unsuitable for gene expression analysis of synovial inflammation due to sampling of non-inflamed parts of the tissue. Removing these biopsies reduced the average number of differentially expressed genes between the orthopedic biopsies from 455 to 171, in comparison with 143 for the arthroscopic biopsies. Hierarchical clustering analysis showed that the remaining orthopedic and arthroscopic biopsies had gene expression signatures that were unique for each patient, apparently reflecting patient variation rather than tissue heterogeneity. Subsets of genes found to vary between biopsies were investigated for overrepresentation of biological processes by using gene ontology. This revealed representative 'themes' likely to vary between synovial biopsies affected by inflammatory disease.
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32. |
- Lindblad-Toh, Kerstin, et al.
(author)
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A high-resolution map of human evolutionary constraint using 29 mammals
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
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Journal article (peer-reviewed)abstract
- The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
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33. |
- Olczak, Jakub, et al.
(author)
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Artificial intelligence for analyzing orthopedic trauma radiographs Deep learning algorithms-are they on par with humans for diagnosing fractures?
- 2017
-
In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:6, s. 581-586
-
Journal article (peer-reviewed)abstract
- Background and purpose - Recent advances in artificial intelligence (deep learning) have shown remarkable performance in classifying non-medical images, and the technology is believed to be the next technological revolution. So far it has never been applied in an orthopedic setting, and in this study we sought to determine the feasibility of using deep learning for skeletal radiographs. Methods - We extracted 256,000 wrist, hand, and ankle radiographs from Danderyd's Hospital and identified 4 classes: fracture, laterality, body part, and exam view. We then selected 5 openly available deep learning networks that were adapted for these images. The most accurate network was benchmarked against a gold standard for fractures. We furthermore compared the network's performance with 2 senior orthopedic surgeons who reviewed images at the same resolution as the network. Results - All networks exhibited an accuracy of at least 90% when identifying laterality, body part, and exam view. The final accuracy for fractures was estimated at 83% for the best performing network. The network performed similarly to senior orthopedic surgeons when presented with images at the same resolution as the network. The 2 reviewer Cohen's kappa under these conditions was 0.76. Interpretation - This study supports the use for orthopedic radiographs of artificial intelligence, which can perform at a human level. While current implementation lacks important features that surgeons require, e.g. risk of dislocation, classifications, measurements, and combining multiple exam views, these problems have technical solutions that are waiting to be implemented for orthopedics.
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34. |
- Otten, Volker T C, 1973-
(author)
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The Uncemented Cup in Total Hip Arthroplasty : stability, Wear and Osteolysis
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Background: Artificial hip joint replacement has undergone tremendous development in the past 100 years. In the beginning, complications, such as infection and early loosening, were the rule rather than the exception. Today, complications of any sort are rare during the first decade after the operation. Artificial hip joint replacement has been chosen as the "Operation of the Century" and has dramatically improved the quality of life of millions of patients. Unfortunately, in the long-term, prosthesis loosening due to pathological bone resorption (osteolysis) around the prosthesis is still common. Traditionally, the prosthesis is anchored in the bone with bone cement (Plexiglas). However, since this cementation method was suspected to cause late loosening, alternative methods, such as the implantation of so-called uncemented prostheses, have been developed and are being increasingly applied. Because the early movement of a prosthesis (migration) increases the risk of loosening, uncemented cups are often augmented with additional screws. The mechanisms regulating the early and late loosening of uncemented cups are not fully established. Wear particles from the artificial joint and intermittent fluid pressure on the bone appear to accelerate or even cause bone loss and can eventually lead to loosening of the prosthesis. Therefore, screw holes in the uncemented cup have been suspected to be a risk factor.Aims: We have studied whether the additional augmentation of modern uncemented cups with screws, pegs or hydroxyapatite increases the long-term stability, affects the wear rate, influences the development of osteolysis, or has any impact on the risk of cup revision. Furthermore, we investigated whether computed tomography (CT), which is needed to detect osteolysis around the prosthesis, could also be used in the follow-up of migration studies without losing significant precision compared to radiostereometry (RSA), which is the gold standard for these measurements.Patients and Methods: In studies I-III, we evaluated 48 hips (45 patients) randomized to receive cups with or without augmentation. As part of the 14-year follow-up with conventional radiographs of the pelvis, two pairs of stereo radiographs and a CT scan were obtained. Migration and wear were measured by RSA. The volume and type of osteolysis were determined on CT. Furthermore, we calculated the precision and limit of agreement of RSA and CT to compare these two modalities as tools for migration measurements.In study IV, we compared the risk of cup revision between 10,371 uncemented cups with and 12,354 without screw holes, using data from the Swedish Hip Arthroplasty Register.Results: Study I: Cup stability was equally good regardless of cup augmentation. The mean wear rate of the cup liner was high, at 0.21 mm/year, with no significant difference between the groups.Study II: The limit of agreement between CT and RSA was 1.15°, 1.51°, and 0.70° for rotation and 0.46, 0.43, and 0.52 mm for translation. These results were within the described normal 99% confidence limits for precision in RSA: 0.3° to 2° for rotation and 0.15 to 0.6 mm for translation.Study III: Osteolysis of some degree was visible in all 48 hips on CT. We found three different types of osteolytic lesions: type 1A, absent trabecular bone and a sclerotic border around the lesion; type 1B, absent trabecular bone and no sclerotic border; and type 2, reduced radiodensity and reduced trabecular number. Cups with screw holes were surrounded with larger osteolytic lesions, and osteolysis around these cups was more likely to be a type 1A lesion.Study IV: Cups without screw holes showed a decreased risk of cup revision (implant exchange or removal) due to any reason at both 2 years (adjusted hazard ratio, HR: 0.6, confidence interval, CI: 0.5-0.8) and 10 years (HR: 0.7, CI: 0.5- 0.9). However, for aseptic loosening, there was no significant difference between cups with and without screw holes, with an implant survival rate of 99.9% (CI: 99.8-99.9) at 2 years and 99.1% (CI: 98.6-99.7) at 10 years.Conclusion: Uncemented cups augmented with screws, pegs, or hydroxyapatite do not have improved long-term stability compared with cups with press-fit only. Unsealed screw holes in uncemented cups appear to be a risk factor for the development of larger osteolytic lesions. CT showed three different types of osteolytic lesions. The risk of aseptic loosening for modern uncemented cup designs is very low, and cups without additional augmentation do not have an increased revision rate. In contrast, the risk of cup revision for any reason was higher for cups with screw holes. CT can be used for migration studies for the longitudinal evaluation of patients with tantalum markers with precision comparable to that of RSA.
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35. |
- Sisask, Gregor, 1951-
(author)
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Bone Development and the Nervous System
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Innervation of bone influence bone modeling, growth and remodeling. Pro-inflammatory cytokines released after tissue trauma are recognized as neurotrophic factors as well as factors influencing bone formation. The Wnt signaling pathway, essential for cell migration during embryogenesis is found to influence bone formation during fracture healing. Alterations in growth and bone formation are seen in denervating disorders and in manipulated Wnt signaling. The aim of the present thesis was to study; sensory and autonomic innervation in the developing skeleton in rats and mice, a possible influence on bone formation in IL-4 and IL-13 depleted mice, and fracture healing in altered Wnt signaling by glycogen synthase-3β inhibition in rats.Bone innervation with sensory and autonomic nerves in modeling and growth follows a predictable and reproducible pattern both in the rat and in the mouse with sensory nerves occurring prior to autonomic nerves in areas with high chondrogenic and osteogenic activity. The time lag in occurrence between sensory and autonomic nerves indicates the importance of developmental timing between different nerve qualities in skeletal ontogeny. These findings give substantial morphologic support for important regulatory effects by the nervous system on bone development.Depletion of the anti-inflammatory cytokines IL-4 and IL-13 production in mice resulted in an inhibited autonomic innervation and lack of implant capillary ingrowth, studied by DXBM implants. In fracture healing no differences between IL-4/13 knockout mice and wild type mice were found concerning fracture callus parameters, biomechanical properties or histology except that sensory and autonomic nerves were found in the bone marrow in knockout mice but not in wild type mice.An altered canonical Wnt signaling was achieved by the GSK-3β inhibitor AR28. The increase in cytoplasmic β-catenin, due to inhibited degradation, resulted in a remarkable anabolic effect both on the fractured bone and on fracture healing. The histological analysis showed that the fractures healed without the usual formation of fibro-cartilage callus. This finding suggests that inhibition of GSK-3β inhibits the differentiation of chondrocytes and instead promotes the differentiation of mesenchymal progenitor cells into osteogenic cells.
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36. |
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37. |
- Sterner, Eila
(author)
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Pressure ulcers - role of the nurse to improve patient safety : prevalence, risk factors, classification and documentation in patients undergoing hip surgery
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Pressure ulcer is a common complication in hip fracture surgery and convalescence. Earlier prevalence studies have demonstrated a lower prevalence in Southern Europe than in Northern Europe. In patients with hip fractures, specific risk factors for developing pressure ulcers, apart from those included in standardised risk assessment are not fully understood. Correct classification of Category I pressure ulcers is a prerequisite for planning preventive measures. It is also mandatory for the reliability of prevalence studies. Until now subjective tests such as finger-press test and visual assessment have been utilised in clinical practice. An objective method has hitherto been lacking. Planning and delivering good nursing care to patients who are at risk of, or already have, manifest pressure ulcers should be built on proper documentation. Degree of documentation of pressure ulcer prevalence and risk factors in patients with hip fractures versus elective hip replacement surgery has hitherto not been investigated. Scrutiny of medical records for these diagnoses and identification of potential differences should therefore be of interest.Aim: - To investigate prevalence and incidence of pressure ulcers upon arrival and at discharge from hospital, and to identify potential intrinsic and extrinsic risk factors for the development of pressure ulcers in patients admitted for hip fracture surgery. To establish the inter-rater reliability between blanching and non-blanching erythema, assessed by two independent assessors. The secondary purpose was to investigate potential correlations between risk factors and pressure ulcers. - To explore if a non-invasive objective method could differentiate between blanching/nonblanching erythema in the sacral area of patients undergoing hip fracture surgery. - To investigate the degree of documentation regarding risk assessment, preventive measures taken, prevalence and severity of pressure ulcers, in patients undergoing surgery for hip fractures or elective hip replacements at admission and during hospital care at an orthopaedic unit.Results: The prevalence of pressure ulcers in Southern Europe was lower compared to Northern Europe. Specific risk factors such as dehydration (p=.005), moist skin (p=.004), pulmonary disease (p=.006) and diabetes (p=.005) were identified. The finger-press test and visual assessment of Category I pressure ulcers were both unreliable methods with low interrater reliability. The proportion of patients with persistent discoloration differed significantly between the assessors from Day 1 to Day 5 (p = .013). Reflectance spectrophotometer used was proven to deliver high precision regarding classification of non-blanchable erythema (Category I pressure ulcers). Documentation of pressure ulcers, risk assessment, body mass index and prevention at admittance was unsatisfactory in patients undergoing hip surgery.
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38. |
- Svedmark, Per, et al.
(author)
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Broken wings : common with the Hardinger plug
- 2002
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In: Acta Orthopaedica Scandinavica. - Oslo, Norway : Taylor & Francis. - 0001-6470. ; 73:4, s. 407-408
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Journal article (peer-reviewed)abstract
- We used the Hardinger occluder plug in 51 consecutive total hip arthroplasties. In 34 hips, 1 or more of the 12 polyethylene wings fractured and could be washed out from the canal. As many as 7 wings were loose in 2 arthroplasties. Although numerous wings were broken, no failure occurred in occlusion. The placement of loose wings in the femoral canal was studied by cementing a Charnley prosthesis in a saw-bone prepared with loose wings. The model was cut into slices. We found that the plastic wings could come into contact with both the bone and prosthesis.
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39. |
- Swedenhammar, E., et al.
(author)
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Reliability and validity of surface EMG assessments combined with isometric muscle strength testing in patients with abdominal rectus diastasis and asymptomatic controls
- 2024
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In: Hernia. - : Springer Nature. - 1265-4906 .- 1248-9204. ; 28:4, s. 1413-1426
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Journal article (peer-reviewed)abstract
- Purpose: Patients with abdominal rectus diastasis (ARD) may have muscular functional impairments, but clinics lack appropriate objective assessment tools. The aim was to establish the relative and absolute reliability, and convergent validity, of muscular activity using Surface Electromyography (SEMG) during isometric abdominal muscle strength testing in patients with ARD and controls without ARD.Methods: Twenty-six patients with ARD were matched for age, sex and BMI with controls without ARD. Participants were tested twice during isometric muscular contractions using SEMG located on six abdominal sites. Mean amplitude, fatigue, and recruitment order were analyzed. Relative reliability was evaluated with Intraclass Correlation Coefficients (ICC), while absolute reliability was estimated by calculating the Standard Error of Measurement and Minimal Detectable Change. Convergent validity was addressed in relation to participant characteristics, functional ability, and symptoms.Results: Mean SEMG amplitude for all abdominal wall muscle contractions showed moderate to excellent relative test–retest reliability, with ICC values ranging from 0.46 to 0.97. In contrast, fatigue and recruitment order displayed poor to moderate relative reliability in both groups. Absolute reliability measures were generally high. A moderate to high convergent validity (ARD: rho-value 0.41–0.70; Controls: rho-value 0.41–0.75) was observed for mean amplitude in relation to a functional sit-to-stand test, abdominal circumference, BMI, back pain, and quality-of-life.Conclusions: The results of applying SEMG during isometric abdominal muscle support practicing the method in clinics, although additional development is needed with further standardization and more functional testing. Furthermore, the method demonstrates construct validity in patients with ARD and in age- and sex-matched controls.
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40. |
- Tsai, Jon A., et al.
(author)
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Albumin-bound lipids induce free cytoplasmic calcium oscillations in human osteoblast-like cells
- 2007
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In: Cell Biochemistry and Function. - : Wiley. - 0263-6484 .- 1099-0844. ; 25:3, s. 245-249
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Journal article (peer-reviewed)abstract
- [Ca2+](i) oscillations were found in human osteoblast-like cells (hOB cells) exposed to high-lipid bovine serum albumin (BSA), but not when exposed to low-lipid BSA. These [Ca2+](i) oscillations were inhibited by heptanol and suramin, which implies that gap junctions and purinergic signalling may be important for these [Ca2+](i) oscillations. The high-lipid BSA preparation that was used contains arachidonic acid. [Ca2+](i) oscillations could be induced by low lipid albumin with arachidonic acid added. The albumin-bound lipids were also important for osteoblast growth since DNA synthesis and the total cell protein content was higher in hOB cells exposed to high-lipid BSA. The effect of arachidonic acid on hOB cell proliferation was bone-donor dependent; both stimulatory and inhibitory effects were observed. The physiological importance of albumin-bound lipids is unclear; given that albumin has only minimal contact with osteoblasts under normal conditions. Only when bone capillaries are disrupted, e.g. during a fracture, would significant amounts of albumin reach osteoblasts. Albumin-bound lipids could therefore contribute to stimulation of osteoblast proliferation during fracture healing.
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41. |
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42. |
- Weiss, Rüdiger J., et al.
(author)
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Decreasing incidence of tibial shaft fractures between 1998 and 2004 : information based on 10,627 Swedish inpatients
- 2008
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In: Acta Orthopaedica. - Lund : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 79:4, s. 526-533
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Journal article (peer-reviewed)abstract
- Background and purpose There is a lack of national epidemiological data on the characteristics of patients with tibial shaft fractures. We therefore analyzed data on Swedish patients with tibial shaft fractures in this nationwide population study based on data from 1998 through 2004. Methods Data on all patients with tibial shaft fractures were extracted from the Swedish National Hospital Discharge Register. Results We identified 10,627 hospital admissions for tibial shaft fractures, corresponding to an annual incidence rate of 17 per 100,000 person-years (pyr). The number of hospital admissions decreased by 12% during the period 1998-2004, mostly from a reduction in male incidence. The median (SD) age at admission was 28 (22) years for men and 51 (26) years for women. The two major mechanisms of injury were falls on the same level (48%) and transport accidents (21%). Surgical procedures were dominated by osteosynthesis with nail (48%), followed by closed reduction and plaster cast (27%), and external fixation (12%). 12% of all tibial shaft fractures were classified as open, corresponding to an incidence rate of 2.3 per 100,000 pyr, which declined during 1998-2004. Interpretation This nationwide study of tibial shaft fractures shows a falling off of fracture incidence, a finding that can be used to advantage by healthcare providers. In a recent review, the annual incidence of tibial shaft fractures was reported to be 22 per 100,000 inhabitants (Court-Brown and Caesar 2006). To date, rather few epidemiological studies have been undertaken to examine the incidence of this injury (Knowelden et al. 1964, Bengner et al. 1990, Donaldson et al. 1990, Court-Brown and McBirnie 1995, Emami et al. 1996, Singer et al. 1998, van Staa et al. 2001), and with varying results. Most of the earlier epidemiological studies were retrospective or case series from single hospitals, and prior to the present study no analyses on a nationwide basis had been undertaken.Basic epidemiological data on frequency and distribution, mechanisms of injury, surgical procedures, and on temporal variations are of importance in assisting the planning and delivery of healthcare. The purpose of this investigation was to provide an update on incidence, admissions, causes of fracture, and operation of these fractures on a nationwide basis in Sweden during the period 1998-2004.
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43. |
- Weiss, Rüdiger J., et al.
(author)
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Gait pattern in rheumatoid arthritis
- 2008
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In: Gait & Posture. - Clare, Ireland : Elsevier. - 0966-6362 .- 1879-2219. ; 28:2, s. 229-234
-
Journal article (peer-reviewed)abstract
- The purpose of this study was to analyse kinematic and kinetic gait changes in rheumatoid arthritis (RA) patients in comparison to healthy controls and to examine whether levels of functional disability (Health Assessment Questionnaire (HAQ)-scores) were associated with gait parameters. Using a three-dimensional motion analysis system, kinematic and kinetic gait parameters were measured in 50 RA patients and 37 healthy controls. There was a significant reduction in joint motions, joint moments and work in the RA cohort compared with healthy controls. The following joint motions were decreased: hip flexion-extension range (Delta6 degrees ), hip abduction (Delta4 degrees ), knee flexion-extension range (Delta8 degrees ) and ankle plantarflexion (Delta10 degrees ). The following joint moments were reduced: hip extensor (Delta0.30Nm/kg) and flexor (Delta0.20Nm/kg), knee extensor (Delta0.11Nm/kg) and flexor (Delta0.13Nm/kg), and ankle plantarflexor (Delta0.44Nm/kg). Work was lower in hip positive work (Delta0.07J/kg), knee negative work (Delta0.08J/kg) and ankle positive work (Delta0.15J/kg). Correlations were fair although significant between HAQ and hip flexion-extension range, hip abduction, knee flexion-extension range, hip abductor moment, stride length, step length and single support (r=-0.30 to -0.38, p<0.05). Our findings suggest that RA patients have overall less joint movement and specifically restricted joint moments and work across the large joints of the lower limbs during walking than healthy controls. There were only fair associations between levels of functional disability and gait parameters. The findings of this study help to improve the understanding how RA affects gait changes in the lower limbs.
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44. |
- Weiss, Rudiger J., et al.
(author)
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Survival of uncemented acetabular monoblock cups Evaluation of 210 hips in the Swedish Hip Arthroplasty Register
- 2012
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 83:3, s. 214-219
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Journal article (peer-reviewed)abstract
- Background and purpose Monoblock acetabular cups represent a subtype of uncemented cups with the polyethylene liner molded into a metal shell, thus eliminating-or at least minimizing-potential backside wear. We hypothesized that the use of mono block cups could reduce the incidence of osteolysis and aseptic loosening, and thus improve survival compared to modular designs. Patients and methods We identified all 210 primary total hip arthroplasty (THA) procedures in the Swedish Hip Arthroplasty Register that used uncemented monoblock cups during the period 1999-2010. Kaplan-Meier and Cox regression analyses with adjustment for age, sex, and other variables were used to calculate survival rates and adjusted hazard ratios (HRs) of the revision risk for any reason. 1,130 modular cups, inserted during the same time period, were used as a control group. Results There was a nearly equal sex distribution in both groups. Median age at the index operation was 47 years in the monoblock group and 56 years in the control group (p < 0.001). The cumulative 5-year survival with any revision as the endpoint was 95% (95% CI: 91-98) for monoblock cups and 97% (CI: 96-98) for modular cups (p = 0.6). The adjusted HR for revision of monoblock cups compared to modular cups was 2 (CI: 0.8-6; p = 0.1). The use of 28-mm prosthesis heads rather than 22-mm heads reduced the risk of cup revision (HR = 0.2, CI: 0.1-0.5; p = 0.001). Interpretation Both cups showed good medium-term survival rates. There was no statistically significant difference in revision risk between the cup designs. Further review of the current patient population is warranted to determine the long-term durability and risk of revision of monoblock cup designs.
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45. |
- Wild, Philipp S., et al.
(author)
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A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease
- 2011
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In: Circulation: Cardiovascular Genetics. - : American Heart Association/Lippincott, Williams & Wilkins. - 1942-325X .- 1942-3268. ; 4:4, s. 203-403
-
Journal article (peer-reviewed)abstract
- Background-eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). Methods and Results-In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7 x 10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3 x 10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4 x 10(-3)). Conclusions-The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD. (Circ Cardiovasc Genet. 2011;4:403-412.)
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46. |
- Wretenberg, Per, 1963-, et al.
(author)
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Radial head prosthesis after fracture of radial head with associated elbow instability
- 2006
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In: Archives of Orthopaedic and Trauma Surgery. - New York, USA : Springer. - 0936-8051 .- 1434-3916. ; 126:3, s. 145-149
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Journal article (peer-reviewed)abstract
- Introduction: Fractures of the radial head and associated elbow instability can be treated with operation with radial head prosthesis. In this study, we evaluate function 1-7 years after implantation and also function after removal of five prostheses.Material and methods: Eighteen patients with radial head fracture and associated elbow instability were evaluated 3.7 years (1-7) after implantation of a radial head prosthesis. Pain at rest and during activity was measured with a visual analogue scale (VAS). Test of stability and neurological examination was done manually as well as measurement of the range of motion, using a goniometer. Activity of daily living (ADL) was estimated using five questions where the answers were graded between 1 and 3. The patients were asked to grade their general satisfaction according to the following scale; very satisfied, satisfied, not satisfied, disappointed. Plain X-rays were taken and 14 patients agreed to have their elbow strength evaluated using the validated BTE work simulator.Results: Five prostheses had been extracted due to poor range of motion. All these patients improved after extraction. All elbows were stable. No patient with extracted prosthesis had VAS score >2. The mean extension defect for this group was 15 degrees (5-25) compared to the mean extension defect for the 13 patients with the prosthesis still in place 15 degrees (0-40). The highest VAS score for the patients with prosthesis was five but the mean as low as 0.8. In the whole group, 13 patients were pain free. ADL function was good in general. The X-rays of the prostheses, still in place, showed radiolucent lines in 7 of the 13 patients. In the whole group, there was a significant decrease in supination, flexion and extension strength (P<0.01, P<0.01, P<0.05).Discussion: Radial head prosthesis works as a spacer after fracture of the radial head and associated instability. If range of motion is much restricted post-operatively, the prosthesis can be removed with improved function as result.
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47. |
- Yang, Jian, et al.
(author)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
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Journal article (peer-reviewed)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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