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| 2. |
- 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. |
- Pilgaard, K., et al.
(författare)
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The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men
- 2009
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:7, s. 1298-1307
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Tidskriftsartikel (refereegranskat)abstract
- We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene. We undertook genotyping of 81 healthy young Danish men for rs7903146 of TCF7L2 and carried out various beta cell tests including: 24 h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic and peripheral insulin action. Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p < 0.05) and reduced insulin secretion relative to glucose during a mixed meal test (beta index: p < 0.003), but not during an IVGTT. This was further supported by reduced late-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p < 0.02) suggesting altered alpha cell function. Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2.
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| 4. |
- Böhlen, Till Tobias, et al.
(författare)
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Investigating the robustness of ion beam therapy treatment plans to uncertainties in biological treatment parameters
- 2012
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 57:23, s. 7983-8004
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Tidskriftsartikel (refereegranskat)abstract
- Uncertainties in determining clinically-used relative biological effectiveness (RBE) values for ion beam therapy carry the risk of absolute and relative misestimations of RBE-weighted doses for clinical scenarios. The present study assesses the consequences of hypothetical misestimations of input parameters to the RBE modelling for carbon ion treatment plans by a variational approach. The impact of the variations on resulting cell survival and RBE values is evaluated as a function of the remaining ion range. In addition, the sensitivity to misestimations in RBE modelling is compared for single fields and two opposed fields using differing optimization criteria. It is demonstrated for single treatment fields that moderate variations (up to ±50%) of representative nominal input parameters for four tumours result mainly in a misestimation of the RBE-weighted dose in the planning target volume (PTV) by a constant factor and only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation quality in the PTV eases the clinical importance of uncertainties in the radiobiological treatment parameters as for such a condition uncertainties tend to result only in a systematic misestimation of RBE-weighted dose in the PTV by a constant factor. Two opposed carbon ion fields with a constant RBE in the PTV are found to result in rather robust conditions. Treatments using two ion species may be used to achieve a constant RBE in the PTV irrespective of the size and depth of the spread-out Bragg peak.
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| 5. |
- Eckhardt, CL, et al.
(författare)
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Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:11, s. 1954-1962
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients. These findings are highly relevant for clinical practice, as they facilitate identification of high-risk patients based on F8 genotype.
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| 6. |
- Jacobsen, S. C., et al.
(författare)
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Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:12, s. 3341-3349
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Tidskriftsartikel (refereegranskat)abstract
- Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle. Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR. HFO introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a maximum methylation change of 13.0 percentage points. The HFO-induced methylation changes were only partly and non-significantly reversed after 6-8 weeks. Alterations in DNA methylation levels primarily affected genes involved in inflammation, the reproductive system and cancer. Few gene expression changes were observed and these had poor correlation to DNA methylation. The genome-wide DNA methylation changes induced by the short-term HFO diet could have implications for our understanding of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases. The slow reversibility suggests a methylation build-up with HFO, which over time may influence gene expression levels.
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| 7. |
- Luttik, M. L. A., et al.
(författare)
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Design and methodology of the COACH-2 (Comparative study on guideline adherence and patient compliance in heart failure patients) study: HF clinics versus primary care in stable patients on optimal therapy
- 2012
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Ingår i: NETHERLANDS HEART JOURNAL. - : Springer Verlag (Germany). - 1568-5888 .- 1876-6250. ; 20:7-8, s. 307-312
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Tidskriftsartikel (refereegranskat)abstract
- Since the number of heart failure (HF) patients is still growing and long-term treatment of HF patients is necessary, it is important to initiate effective ways for structural involvement of primary care services in HF management programs. However, evidence on whether and when patients can be referred back to be managed in primary care is lacking. To determine whether long-term patient management in primary care, after initial optimisation of pharmacological and non-pharmacological treatment in a specialised HF clinic, is equally effective as long-term management in a specialised HF clinic in terms of guideline adherence and patient compliance. The study is designed as a randomised, controlled, non-inferiority trial. Two-hundred patients will be randomly assigned to be managed and followed in primary care or in a HFclinic. Patients are eligible to participate if they are (1) clinically stable, (2) optimally up-titrated on medication (according to ESC guidelines) and, (3) have received optimal education and counselling on pre-specified issues regarding HF and its treatment. Furthermore, close cooperation between secondary and primary care in terms of back referral to or consultation of the HF clinic will be provided.The primary outcome will be prescriber adherence and patient compliance with medication after 12 months. Secondary outcomes measures will be readmission rate, mortality, quality of life and patient compliance with other lifestyle changes. The results of the study will add to the understanding of the role of primary care and HF clinics in the long-term follow-up of HF patients.
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| 8. |
- Luttik, Marie Louise A., et al.
(författare)
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Long-term follow-up in optimally treated and stable heart failure patients: primary care vs. heart failure clinic. Results of the COACH-2 study
- 2014
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Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B / Wiley: 12 months. - 1388-9842 .- 1879-0844. ; 16:11, s. 1241-1248
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Tidskriftsartikel (refereegranskat)abstract
- AimsIt has been suggested that home-based heart failure (HF) management in primary care may be an alternative to clinic-based management in HF patients. However, little is known about adherence to HF guidelines and adherence to the medication regimen in these home-based programmes. The aim of the current study was to determine whether long-term follow-up and treatment in primary care is equally effective as follow-up at a specialized HF clinic in terms of guideline adherence and patient adherence, in HF patients initially managed and up-titrated to optimal treatment at a specialized HF clinic. Methods and resultsWe conducted a multicentre, randomized, controlled study in 189 HF patients (62% male, age 72 11 years), who were assigned to follow-up either in primary care (n = 97) or in a HF clinic (n = 92). After 12 months, no differences between guideline adherence, as estimated by the Guideline Adherence Indicator (GAI-3), and patient adherence, in terms of the medication possession ratio (MPR), were found between treatment groups. There was no difference in the number of deaths (n = 12 in primary care and n = 8 in the HF clinic; P = 0.48), and hospital readmissions for cardiovascular (CV) reasons were also similar. The total number of unplanned non-CV hospital readmissions, however, tended to be higher in the primary care group (n = 22) than in the HF clinic group (n = 10; P = 0.05). Conclusionsless thanp id="ejhf173-para-0003"greater thanPatients discharged after initial management in a specialized HF clinic can be discharged to primary care for long-term follow-up with regard to maintaining guideline adherence and patient adherence. However, the complexity of the HF syndrome and its associated co-morbidities requires continuous monitoring. Close collaboration between healthcare providers will be crucial in order to provide HF patients with optimal, integrated care.
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| 9. |
- Mairani, A., et al.
(författare)
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A Monte Carlo-based treatment planning tool for proton therapy
- 2013
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 58:8, s. 2471-2490
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Tidskriftsartikel (refereegranskat)abstract
- In the field of radiotherapy, Monte Carlo (MC) particle transport calculations are recognized for their superior accuracy in predicting dose and fluence distributions in patient geometries compared to analytical algorithms which are generally used for treatment planning due to their shorter execution times. In this work, a newly developed MC-based treatment planning (MCTP) tool for proton therapy is proposed to support treatment planning studies and research applications. It allows for single-field and simultaneous multiple-field optimization in realistic treatment scenarios and is based on the MC code FLUKA. Relative biological effectiveness (RBE)-weighted dose is optimized either with the common approach using a constant RBE of 1.1 or using a variable RBE according to radiobiological input tables. A validated reimplementation of the local effect model was used in this work to generate radiobiological input tables. Examples of treatment plans in water phantoms and in patient-CT geometries together with an experimental dosimetric validation of the plans are presented for clinical treatment parameters as used at the Italian National Center for Oncological Hadron Therapy. To conclude, a versatile MCTP tool for proton therapy was developed and validated for realistic patient treatment scenarios against dosimetric measurements and commercial analytical TP calculations. It is aimed to be used in future for research and to support treatment planning at state-of-the-art ion beam therapy facilities.
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| 12. |
- Gillberg, Linn, et al.
(författare)
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Adipose tissue transcriptomics and epigenomics in low birthweight men and controls : role of high-fat overfeeding
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:4, s. 799-812
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Individuals who had a low birthweight (LBW) are at an increased risk of insulin resistance and type 2 diabetes when exposed to high-fat overfeeding (HFO). We studied genome-wide mRNA expression and DNA methylation in subcutaneous adipose tissue (SAT) after 5 days of HFO and after a control diet in 40 young men, of whom 16 had LBW. Methods mRNA expression was analysed using Affymetrix Human Gene 1.0 ST arrays and DNA methylation using Illumina 450K BeadChip arrays. Results We found differential DNA methylation at 53 sites in SAT from LBW vs normal birthweight (NBW) men (false discovery rate < 5%), including sites in the FADS2 and CPLX1 genes previously associated with type 2 diabetes. When we used reference-free cell mixture adjustments to potentially adjust for cell composition, 4,323 sites had differential methylation in LBW vs NBW men. However, no differences in SAT gene expression levels were identified between LBW and NBW men. In the combined group of all 40 participants, 3,276 genes (16.5%) were differentially expressed in SAT after HFO (false discovery rate < 5%) and there was no difference between LBW men and controls. The most strongly upregulated genes were ELOVL6, FADS2 and NNAT; in contrast, INSR, IRS2 and the SLC27A2 fatty acid transporter showed decreased expression after HFO. Interestingly, SLC27A2 expression correlated negatively with diabetes- and obesity-related traits in a replication cohort of 142 individuals. DNA methylation at 652 CpG sites (including in CDK5, IGFBP5 and SLC2A4) was altered in SAT after overfeeding in this and in another cohort. Conclusions/interpretation Young men who had a LBW exhibit epigenetic alterations in their adipose tissue that potentially influence insulin resistance and risk of type 2 diabetes. Short-term overfeeding influences gene transcription and, to some extent, DNA methylation in adipose tissue; there was no major difference in this response between LBW and control participants.
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