| 1. |
- van Velzen, Alice S., et al.
(författare)
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Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients : Results of the INSIGHT case-control study
- 2017
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 15:7, s. 1422-1429
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Tidskriftsartikel (refereegranskat)abstract
- Essentials: Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Summary: Background: Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives: We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods: We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results: Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg-1/ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions: Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically.
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| 2. |
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| 3. |
- von Salzen, Knut, et al.
(författare)
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Clean air policies are key for successfully mitigating Arctic warming
- 2022
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- A tighter integration of modeling frameworks for climate and air quality is urgently needed to assess the impacts of clean air policies on future Arctic and global climate. We combined a new model emulator and comprehensive emissions scenarios for air pollutants and greenhouse gases to assess climate and human health co-benefits of emissions reductions. Fossil fuel use is projected to rapidly decline in an increasingly sustainable world, resulting in far-reaching air quality benefits. Despite human health benefits, reductions in sulfur emissions in a more sustainable world could enhance Arctic warming by 0.8 °C in 2050 relative to the 1995–2014, thereby offsetting climate benefits of greenhouse gas reductions. Targeted and technically feasible emissions reduction opportunities exist for achieving simultaneous climate and human health co-benefits. It would be particularly beneficial to unlock a newly identified mitigation potential for carbon particulate matter, yielding Arctic climate benefits equivalent to those from carbon dioxide reductions by 2050.
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| 4. |
- Eckhardt, C. L., et al.
(författare)
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The Fc gamma receptor IIa R131H polymorphism is associated with inhibitor development in severe hemophilia A
- 2014
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:8, s. 1294-1301
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of factor (F) VIII neutralizing alloantibodies (inhibitors) is a major complication of treatment with FVIII concentrates in hemophilia A and the etiology is still poorly understood. The low-affinity Fc gamma receptors (Fc gamma R), which are expressed on immune cells, provide an important link between cellular and humoral immunity by interacting with IgG subtypes. Genetic variations of the genes encoding Fc gamma Rs (FCGR genes) have been associated with susceptibility to infectious and autoimmune diseases. Objectives: The aim of this study was to investigate the association between genetic variation of FCGR and inhibitor development in severe hemophilia A. Patients/Methods: In this case-control study samples of 85 severe hemophilia A patients (siblings from 44 families) were included. Single nucleotide polymorphisms and copy number variation of the FCGR2 and FCGR3 gene cluster were studied in an FCGR-specific multiplex ligation-dependent probe amplification assay. Frequencies were compared in a generalized estimating equation regression model. Results: Thirty-six patients (42%) had a positive history of inhibitor development. The polymorphism 131R > H in the FCGR2A gene was associated with an increased risk of inhibitor development (odds ratio [OR] per H-allele, 1.8; 95% confidence interval [CI], 1.1-2.9). This association persisted in 29 patients with high titer inhibitors (OR per H-allele, 1.9; 95% CI, 1.2-3.2) and in 44 patients with the F8 intron 22 inversion (OR per H-allele, 2.6; 95% CI, 1.1-6.6). Conclusions: Hemophilia A patients with the HH genotype of the FCGR2A polymorphism 131R > H have a more than 3-fold increased risk of inhibitor development compared with patients with the RR genotype.
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| 5. |
- Elliott, J. A., et al.
(författare)
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Changes in gut hormones, glycaemic response and symptoms after oesophagectomy
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:6, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. Methods: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. Results: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s. e. m.) 17.1(3.2) per cent, P < 0.001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0.014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0.003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0.022). Mean(s. e. m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621.5(71.7) pg/ml; 10 days: 415.1(59.80) pg/ml; 6weeks: 309.0(42.0) pg/ml; 12weeks: 415.8(52.1) pg/ml; 52weeks: 547.4(83.2) pg/ml; P< 0.001) and did not predict weight loss (P = 0.198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52weeks (mean(s. e. m.) insulin AUC0-30 min: fold change 1.7(0.4), 2.0(0.4), 3.5(0.7) and 4.0(0.8) respectively; P = 0.001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0.001), with a 3.3(1.8)-fold increase at 1 year (P < 0.001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0.041) and symptomatic neuroglycopenia (Sigstad score, P = 0.017, R2 = 0.45). GLP-1 AUC predicted loss of weight (P = 0.008, R2 = 0.52) and fat mass (P = 0.010, R2 = 0.64) at 1 year. Conclusion: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.
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| 6. |
- Winiger, Patrik, et al.
(författare)
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Source apportionment of circum-Arctic atmospheric black carbon from isotopes and modeling
- 2019
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Black carbon (BC) contributes to Arctic climate warming, yet source attributions are inaccurate due to lacking observational constraints and uncertainties in emission inventories. Year-round, isotope-constrained observations reveal strong seasonal variations in BC sources with a consistent and synchronous pattern at all Arctic sites. These sources were dominated by emissions from fossil fuel combustion in the winter and by biomass burning in the summer. The annual mean source of BC to the circum-Arctic was 39 +/- 10% from biomass burning. Comparison of transport-model predictions with the observations showed good agreement for BC concentrations, with larger discrepancies for (fossil/biomass burning) sources. The accuracy of simulated BC concentration, but not of origin, points to misallocations of emissions in the emission inventories. The consistency in seasonal source contributions of BC throughout the Arctic provides strong justification for targeted emission reductions to limit the impact of BC on climate warming in the Arctic and beyond.
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