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- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 3. |
- Edfors, R., et al.
(författare)
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Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:5, s. 581-592
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min(-1)/1.73 m(2)were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.
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- Cabrera, C., et al.
(författare)
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Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle
- 2023
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 379, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake.Methods: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing.Results: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF phys-iology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 mu g/L). Analysing the correlation between various iron pa-rameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes.Conclusions: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs.
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| 43. |
- Cangiano, L, et al.
(författare)
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Role of apamin-sensitive k(ca) channels for reticulospinal synaptic transmission to motoneuron and for the afterhyperpolarization
- 2002
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 88:1, s. 289-299
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Tidskriftsartikel (refereegranskat)abstract
- Single motoneurons and pairs of a presynaptic reticulospinal axon and a postsynaptic motoneuron were recorded in the isolated lamprey spinal cord, to investigate the role of calcium-dependent K+ channels (KCa) during the afterhyperpolarization following the action potential (AHP), and glutamatergic synaptic transmission on the dendritic level. The AHP consists of a fast phase due to transient K+ channels (fAHP) and a slower phase lasting 100–200 ms (sAHP), being the main determinant of spike frequency regulation. We now present evidence that the sAHP has two components. The larger part, around 80%, is abolished by superfusion of Cd2+ (blocker of voltage-dependent Ca2+ channels), by intracellular injection of 1,2-bis-( 2-aminophenoxy)-ethane- N,N,N′,N′-tetraacetic acid (BAPTA; fast Ca2+ chelator), and by apamin (selective toxin for KCa channels of the SK subtype). While 80% of the sAHP is thus due to KCa channels, the remaining 20% is not mediated by Ca2+, either entering through voltage-dependent Ca2+ channels or released from intracellular Ca2+ stores. This Ca2+-independent sAHP component has a similar time course as the KCa portion and is not due to a Cl− conductance. It may be caused by Na+-activated K+ channels. Glutamatergic excitatory postsynaptic potentials (EPSPs) evoked by single reticulospinal axons give rise to a local Ca2+ increase in the postsynaptic dendrite, mediated in part by N-methyl-d-aspartate (NMDA) receptors. The Ca2+ levels remain elevated for several hundred milliseconds and could be expected to activate KCa channels. If so, this activation should cause a local conductance increase in the dendrite that would shunt EPSPs following the first EPSP in a spike train. We have tested this in reticulospinal/motoneuronal pairs, by stimulating the presynaptic axon with spike trains at different frequencies. We compared the first EPSP and the following EPSPs in the control and after blockade with apamin. No difference was observed in EPSP amplitude or shape before and after apamin, either in normal Ringer or in Mg2+-free Ringer removing the voltage-dependent block of NMDA receptors. In conclusion, the local Ca2+ entry during reticulospinal EPSPs does not cause an activation of KCa channels sufficient to affect the efficacy of synaptic transmission. Thus the integration of synaptic signals at the dendritic level in motoneurons appears simpler than would otherwise have been the case.
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| 45. |
- Chadwick, D., et al.
(författare)
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Digital inclusion and participation of people with intellectual disabilities during COVID-19 : A rapid review and international bricolage
- 2022
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Ingår i: Journal of Policy and Practice in Intellectual Disabilities. - : Wiley. - 1741-1122 .- 1741-1130. ; 19:3, s. 242-256
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has meant a rapid transfer of everyday activities to the online world. Information and communication technologies (ICTs) have become more embedded than ever in people's lives. This investigation addresses how this change has affected the lives of people with intellectual disabilities (ID). A two-step design was used. A rapid review was conducted on empirical studies published between January 2019 and June 2021. Search terms related to ID, ICT use and COVID-19. A qualitative international bricolage was also conducted corresponding to author nationalities. Data gathered from the review and bricolage were analysed separately using thematic analysis and relationally synthesised. Digital solutions to provide access to COVID-19 information and guidance seemed inadequate but were seldom empirically studied. Digital poverty, literacy and exclusion remain significant issues for people with ID internationally. People and their carers experienced reduced and removed service provision, loneliness and impoverished daily lives during the pandemic; amelioration of which was facilitated by digital solutions. One solution often used was videoconferencing. Prior experience of digital participation, adequate finances, connection, support and digital literacy mentoring for both people with ID and those providing services and support facilitated digital inclusion. Digital exclusion during COVID-19 was exacerbated by sociopolitical, structural, individual and support-related barriers. Although awareness of digital exclusion appears to have been raised, the extent to which this has led to action and change remains unclear. Despite digital exclusion and digital participation benefitting continuation of life, social and emotional well-being and autonomy, COVID-19 has not provided the impetus to eradicate digital poverty for people with ID. Governmental support, digital education, creativity and problem solving are required to enable people with ID the human right to be included in the digital world at this essential time and into the future.
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| 46. |
- Charchar, Fadi J., et al.
(författare)
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Lifestyle management of hypertension : International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension
- 2024
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Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 42:1, s. 23-49
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.
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| 47. |
- Cheng, X F, et al.
(författare)
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Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA.
- 1995
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Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 77:2, s. 149-64
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Tidskriftsartikel (refereegranskat)abstract
- The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.
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| 48. |
- Dagnegård, H.H., et al.
(författare)
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Survival after aortic root replacement with a stentless xenograft is determined by patient characteristics
- 2022
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Mosby Inc.; Elsevier Inc.. - 0022-5223 .- 1097-685X. ; 164:6, s. 1712-1724
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Our objective was to examine intermediate-term survival and reinterventions in unselected patients, stratified according to indication, who received a Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis as a full aortic root replacement. Methods: Data from medical records were retrospectively collected for patients who had aortic root replacement using Freestyle bioprostheses between 1999 and 2018 at 6 North-Atlantic centers. Survival status was extracted from national registries and results stratified according to indication for surgery. Results: We included 1030 implantations in 1008 patients with elective indications for surgery: aneurysm (39.8%), small root (8.3%), and other (13.8%), and urgent/emergent indications: endocarditis (26.7%) and Stanford type A aortic dissection (11.4%). Across indications, 46.3% were nonelective cases and 34.0% were reoperations. Median age was 66.0 (interquartile range, 58.0-71.8) years and median follow-up was 5.0 (interquartile range, 2.6-7.9) years. Thirty-day mortality varied from 2.9% to 27.4% depending on indication. Intermediate survival for 90-day survivors with elective indications were not different from the general population standardized for age and sex (P = .95, 83, and .16 for aneurysms, small roots, and other, respectively). In contrast, patients with endocarditis and type A dissection had excess mortality (P < .001). Freedom from valve reinterventions was 95.0% and 94.4% at 5 and 8 years, respectively. In all, 52 patients (5.2%) underwent reinterventions, most because of endocarditis. Conclusions: At intermediate term follow-up this retrospective study provides further support for the use of the Freestyle bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics. © 2021 The Authors
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| 49. |
- Dorrepaal, E, et al.
(författare)
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Are growth forms consistent predictors of leaf litter quality and decomposability across peatlands along a latitudinal gradient?
- 2005
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Ingår i: Journal of Ecology. - : Wiley. - 1365-2745 .- 0022-0477. ; 93:4, s. 817-828
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Tidskriftsartikel (refereegranskat)abstract
- Plant growth forms are widely used to predict the effects of environmental changes, such as climate warming and increased nitrogen deposition, on plant communities, and the consequences of species shifts for carbon and nutrient cycling. We investigated whether the relationship between growth forms and patterns in litter quality and decomposition are independent of environmental conditions and whether growth forms are as good as litter chemistry at predicting decomposability. We used a natural, latitudinal gradient in NW Europe as a spatial analogue for future increases in temperature and nitrogen availability. Our screening of 70 species typical of Sphagnum-dominated peatlands showed that leaf litters of Sphagnum mosses, evergreen and deciduous shrubs, graminoids and forbs differed significantly in litter chemistry and that the ranking of the growth forms was independent of the region for all litter chemistry variables. Differences among growth forms were usually larger than differences related to the environmental gradient. After 8 and 20 months incubation in outdoor, Sphagnum-based decomposition beds, growth forms generally differed in decomposability, but these patterns varied with latitude. Sphagnum litters decomposed slower than other litters in all regions, again explaining its high representation in organic deposits of peatlands. Forb litters generally decomposed fastest, while the differences among the other growth forms were small, particularly at higher latitudes. Multiple regression analyses showed that growth forms were better at predicting leaf litter decomposition than chemical variables in warm-temperate peatlands with a high N-load, but less so in the subarctic, low-N region. Our results indicate that environmental changes may be less important in determining ecosystem leaf litter chemistry directly than are their indirect effects through changes in the relative abundance of growth forms. However, climatic and nutritional constraints in high-latitude peatlands promote convergence towards nutrient-efficient plant traits, resulting in similar decomposition rates of vascular growth forms despite differences in litter chemistry. The usefulness of the growth-form concept in predicting plant community controls on ecosystem functioning is therefore somewhat limited.
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