| 1. |
- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)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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| 2. |
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| 3. |
- Bourg, S., et al.
(author)
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ACSEPT-Partitioning technologies and actinide science: Towards pilot facilities in Europe
- 2011
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In: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493. ; 241:9, s. 3427-3435
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Journal article (peer-reviewed)abstract
- Actinide recycling by separation and transmutation is considered worldwide and particularly in several European countries as one of the most promising strategies to reduce the inventory of radioactive waste and to optimise the use of natural resources. With its multidisciplinary consortium of 34 partners from 12 European countries plus Australia and Japan, the European Research Project ACSEPT (Actinide recycling by SEParation and Transmutation) aims at contributing to the development of this strategy by studying both hydrometallurgical and pyrochemical partitioning routes. ACSEPT is organised into three technical domains: (i) Considering technically mature aqueous separation processes, ACSEPT works to optimise and select the most promising ones dedicated either to actinide partitioning (for the heterogeneous recycling of actinides in ADS target or specific actinide bearing blanket fuels in fast reactor) or to grouped actinide separation (for the homogeneous recycling of the actinides in fast reactor fuels). In addition, dissolution and conversion studies are underway taking into account the specific requirements of these specific fuels. (ii) Concerning pyrochemical separation processes. ACSEPT focuses on the enhancement of the two reference cores processes selected within FP6-EUROPART. R&D efforts are also devoted to key scientific and technical issues compulsory to set up a complete separation process (head-end steps, salt treatment for recycling and waste management). (iii) By integrating all the experimental results in engineering and system studies, both in hydro and pyro domains, ACSEPT will deliver relevant flowsheets and recommendations to prepare for future demonstrations at a pilot level. After more than two years of work, significant progress was achieved in process development with the demonstration of the SANEX and innovative SANEX flowsheets. Chemical systems were selected for GANEX and are under study. In addition, efforts were made to increase collaborations, mutualise and homogenise procedures and share good practices. Based on these assessments, it is now time to look at the future challenges to overcome. A training and education program is implemented to share the knowledge among the partitioning community, present and future generations of researchers. Specific attention is paid to the funding of post-doctorate fellowships, two having been appointed respectively at the end of 2008 and at the end of 2009. Through this training and education programme, the first ACSEPT International Workshop was organised last March in Lisbon, Portugal. It gave an emphasis to young researchers' contributions (two thirds of the contributions) and allowed young scientists to meet and exchange with international recognised experts.
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| 6. |
- Main, Chris J., et al.
(author)
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Implementation Science and Employer Disability Practices : Embedding Implementation Factors in Research Designs
- 2016
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In: Journal of occupational rehabilitation. - : Springer-Verlag New York. - 1053-0487 .- 1573-3688. ; 26:4, s. 448-464
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Journal article (peer-reviewed)abstract
- Purpose: For work disability research to have an impact on employer policies and practices it is important for such research to acknowledge and incorporate relevant aspects of the workplace. The goal of this article is to summarize recent theoretical and methodological advances in the field of Implementation Science, relate these to research of employer disability management practices, and recommend future research priorities.Methods: The authors participated in a year-long collaboration culminating in an invited 3-day conference, “Improving Research of Employer Practices to Prevent Disability”, held October 14–16, 2015, in Hopkinton, MA, USA. The collaboration included a topical review of the literature, group conference calls to identify key areas and challenges, drafting of initial documents, review of industry publications, and a conference presentation that included feedback from peer researchers and a question/answer session with a special panel of knowledge experts with direct employer experience.Results: A 4-phase implementation model including both outer and inner contexts was adopted as the most appropriate conceptual framework, and aligned well with the set of process evaluation factors described in both the work disability prevention literature and the grey literature. Innovative interventions involving disability risk screening and psychologically-based interventions have been slow to gain traction among employers and insurers. Research recommendations to address this are : (1) to assess organizational culture and readiness for change in addition to individual factors; (2) to conduct process evaluations alongside controlled trials; (3) to analyze decision-making factors among stakeholders; and (4) to solicit input from employers and insurers during early phases of study design.Conclusions: Future research interventions involving workplace support and involvement to prevent disability may be more feasible for implementation if organizational decision-making factors are imbedded in research designs and interventions are developed to take account of these influences.
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| 7. |
- Sollerhed, A. -C, et al.
(author)
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Movement and physical activity in early childhood education and care policies of five nordic countries
- 2021
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:24
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Journal article (peer-reviewed)abstract
- The purpose of this study was to examine the values of movement and physical activity (MoPA) using government policy documents (e.g., laws and curricula) on early childhood education and care (ECEC) from Denmark, Finland, Iceland, Norway, and Sweden. This descriptive, comparative study was designed based on curriculum theory and used word count and content analyses to identify similarities and differences in the occurrence of MoPA in the ECEC policies of Nordic countries. Seven terms were identified as MoPA-related in Nordic policy documents. These terms occurred in various content contexts: development, environment, expression, health and well-being, learning and play, albeit sparsely. MoPA was referred to as both a goal in and of itself and as a means of achieving other goals (e.g., learning or development in another area). Formulations specifically dedicated to MoPA as a goal were present in the Danish and Finnish curricula and, to some extent, also in the Norwegian curriculum, while the Icelandic and Swedish curricula mentioned MoPA mostly as a means. Findings indicated that MoPA, which is important for children’s development, health, and well-being, is a low-priority value, to varying degrees, in the ECEC policies enacted by Nordic countries and the guidance provided to educators and stakeholders therein is inexplicit.
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| 8. |
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| 9. |
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| 10. |
- Sundman, E, et al.
(author)
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The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium
- 2000
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In: Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 1528-1175 .- 0003-3022. ; 92:4, s. 977-977
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Journal article (peer-reviewed)abstract
- BACKGROUND: Residual neuromuscular block caused by vecuronium alters pharyngeal function and impairs airway protection. The primary objectives of this investigation were to radiographically evaluate the swallowing act and to record the incidence of and the mechanism behind pharyngeal dysfunction during partial neuromuscular block. The secondary objective was to evaluate the effect of atracurium on pharyngeal function. METHODS: Twenty healthy volunteers were studied while awake during liquid-contrast bolus swallowing. The incidence of pharyngeal dysfunction was studied by fluoroscopy. The initiation of the swallowing process, the pharyngeal coordination, and the bolus transit time were evaluated. Simultaneous manometry was used to document pressure changes at the tongue base, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, an intravenous infusion of atracurium was administered to obtain train-of-four ratios (T4/T1) of 0.60, 0.70, and 0.80, followed by recovery to a train-of-four ratio of more than 0.90. RESULTS: The incidence of pharyngeal dysfunction was 6% during the control recordings and increased (P < 0.05) to 28%, 17%, and 20% at train-of-four ratios 0.60, 0.70, and 0.80, respectively. After recovery to a train-of-four ratio of more than 0.90, the incidence was 13%. Pharyngeal dysfunction occurred in 74 of 444 swallows, the majority (80%) resulting in laryngeal penetration. The initiation of the swallowing reflex was impaired during partial paralysis (P = 0.0081). The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 (P < 0.01). A marked reduction in the upper esophageal sphincter resting tone was found, as well as a reduced contraction force in the pharyngeal constrictor muscles. The bolus transit time did not change significantly. CONCLUSION: Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing. The mechanism behind the pharyngeal dysfunction is a delayed initiation of the swallowing reflex, impaired pharyngeal muscle function, and impaired coordination. The majority of misdirected swallows resulted in penetration of bolus to the larynx.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Boden, K., et al.
(author)
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Swallowing and respiratory pattern in young healthy individuals recorded with high temporal resolution
- 2009
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:11, s. 1163-1163
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Journal article (peer-reviewed)abstract
- P>The coordination of swallowing and respiration is essential for a safe swallow. Swallowing consists of several subsecond events. To study this, it is important to use modalities with high temporal resolution. In this study, we have examined young healthy individuals with simultaneous videofluoroscopy, videomanometry and respiratory recording, all with high temporal resolution. The onset of 13 predetermined swallowing and respiratory events and the surrounding respiratory phase pattern were studied in different body positions and during different respiratory drives. An increased respiratory drive was induced by breathing 5% CO2. The results demonstrated a highly repeatable and fixed temporal coordination of the swallowing pattern despite body position and respiratory drive. Previous studies have demonstrated a period of centrally controlled apnoea during swallowing. This apnoea period has a variable length, varying from 1 to 5 s. During increased respiratory drive, we could demonstrate a significantly shorter period of apnoea during swallowing, mainly due to an earlier resumption of respiration. The high temporal recordings in this study have revealed that swallowing during expiration is present basically in all healthy individuals. This swallowing respiratory pattern seems to be appropriate for a safe swallow. This knowledge will be used as a reference for future studies on how swallowing and respiratory coordination might be altered due to ageing and diseases.
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| 18. |
- Bouamar, R., et al.
(author)
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Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
- 2013
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 13:5, s. 1253-1261
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Journal article (peer-reviewed)abstract
- Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac.
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| 19. |
- Brännström, Mats, 1958, et al.
(author)
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Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial.
- 2020
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In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:8
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Journal article (peer-reviewed)abstract
- Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017-2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5-6.6), 300 mL (150-600), 43.5 mL/min (20-125)/37.5 mL/min (10-98), and 6 days (5-9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure.
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| 20. |
- Cantarovich, M, et al.
(author)
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First global forum on education on organ donation and transplantation for schools.
- 2012
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In: Pediatric Transplantation. - : Wiley. - 1399-3046 .- 1397-3142.
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Journal article (peer-reviewed)abstract
- The Transplantation Society, in collaboration with the Canadian Society of Transplantation, organized a forum on education on ODT for schools. The forum included participants from around the world, school boards, and representatives from different religions. Participants presented on their countries' experience in the area of education on ODT. Working groups discussed about technologies for education, principles for sharing of resources globally, and relationships between education, and health authorities and non-governmental organizations. The forum concluded with a discussion about how to best help existing programs and those wishing to start educational programs on ODT.
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| 21. |
- Cedborg, A. I. Hardemark, et al.
(author)
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Breathing and swallowing in normal man - effects of changes in body position, bolus types, and respiratory drive
- 2010
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1201-1201
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Journal article (peer-reviewed)abstract
- Background Coordination of breathing and swallowing is essential for airway protection and dyscoordination may cause morbidity and mortality. Methods Using a recently developed technique for high accuracy respiratory measurements of airflow during swallowing, we investigated the effects of body position (upright vs left lateral), bolus type (spontaneously swallowed saliva vs water), and respiratory drive (normo- vs hypercapnia) on coordination of breathing and swallowing in 32 healthy volunteers. Key Results Swallows were in all cases (100%) proceded by expiration and 98% were also followed by expiration, regardless of body position, bolus type, or respiratory drive. While the endpoint of postswallow apnea correlated well to the endpoint of pharyngeal swallowing, duration of preswallow apnea was highly variable. In a small fraction of swallows followed by inspiration (3%), the expiratory phase before swallowing and duration of postswallow apnea was significantly longer. Body position and respiratory drive affected the increase in upper esophageal sphincter tone during inspiration. Increased respiratory drive also reduced swallowing frequency and shortened duration of preswallow apnea. Water swallows had longer duration of preswallow apnea. Conclusions & Inferences Swallowing occurs during the expiratory phase of respiration, and the fraction of swallows preceded and followed by expiration approach 100% in healthy humans. This integration between breathing and swallowing remains unchanged regardless of body position, bolus characteristics, or respiratory drive. Our results provide a platform for future studies aiming at understanding how this integration is changed by aging, diseases, and drugs.
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| 22. |
- Che, K. F., et al.
(author)
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The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
- 2018
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In: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 132:9, s. 959-983
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Journal article (peer-reviewed)abstract
- Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor kappa B (NF-kappa B); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-kappa B and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
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| 23. |
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| 24. |
- Colom, Helena, et al.
(author)
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Pharmacokinetic modeling of enterohepatic circulation of mycophenolic acid in renal transplant recipients.
- 2014
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 85:6, s. 1434-1443
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Journal article (peer-reviewed)abstract
- Several factors contribute to mycophenolic acid (MPA) between-patient variability. Here we characterize the metabolic pathways of MPA and quantify the effect of combining genetic polymorphism of multidrug-resistant-associated protein-2, demographics, biochemical covariates, co-medication (cyclosporine (CsA) vs. macrolides), and renal function on MPA, 7-O-MPA-glucuronide (MPAG), and acyl-glucuronide (AcMPAG) disposition, in renal transplant recipients, after mycophenolate mofetil. Complete pharmacokinetic profiles from 56 patients (five occasions) were analyzed. Enterohepatic circulation was modeled by transport of MPAG to the absorption site. This transport significantly decreased with increasing CsA trough concentrations (CtroughCsA). MPAG and AcMPAG plasma clearances significantly decreased with renal function. No significant influence of multidrug-resistant-associated protein-2 C24T single-nucleotide polymorphism was found. The model adequately predicted the increase in MPAG/AcMPAG exposures in CsA and macrolide patients with decreased renal function. This resulted in higher MPA exposures in macrolide patients versus CsA patients, and increased MPA exposures with renal function from 25 to 10 ml/min, in macrolide patients, owing to enhanced MPAG enterohepatic circulation. Lower-percentage enterohepatic circulation occurred with higher CtroughCsA and renal function values. The lack of MPA protein-binding modeling did not permit evaluation of the impact of renal function and CtroughCsA on MPA exposures in CsA patients. Thus, dose tailoring of covariates is recommended for target MPA exposure.Kidney International advance online publication, 8 January 2014; doi:10.1038/ki.2013.517.
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| 25. |
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| 26. |
- Diab, R, et al.
(author)
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Effect of triple costimulation blockade on islet allograft survival in sensitized mice.
- 2010
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In: Transplantation proceedings. - : Elsevier BV. - 1873-2623 .- 0041-1345. ; 42:6, s. 2109-11
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Journal article (other academic/artistic)abstract
- BACKGROUND: Islet allograft rejection in sensitized recipients is difficult to control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T-cell activities. We examined the effects on islet allograft survival of triple costimulation blockade in presensitized recipient mice. METHODS: C57BL/6 mice were sensitized by transplantation under the kidney capsule or intraperitoneal injection of Balb/c islets. Four weeks after transplantation, sensitization was confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was induced by a single intravenous injection of streptozotocin. Recipients were transplanted with 200 Balb/c islets under the right kidney capsule. Graft function was assessed by daily blood glucose and body weight records. Transplanted animals were divided into 3 treatment groups: group 1, control antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154, CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second day from day -2 to day 8. RESULTS: Naïve mice rejected islet allografts between days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0 and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d; n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10). CONCLUSION: Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA-1 was not sufficient to improve islet allograft survival in sensitized recipients.
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| 27. |
- Edling, C., et al.
(author)
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Long-term follow up of workers exposed to solvents
- 1990
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In: British journal of industrial medicine. - 0007-1072. ; 47:2, s. 75-82
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Journal article (peer-reviewed)abstract
- Long term occupational exposure to organic solvents may cause adverse effects to the central nervous system. This collaborative study between six Swedish departments of occupational medicine examines the overall prognosis in terms of working capacity, symptoms, and psychometric test performance for individuals occupationally exposed to organic solvents. After re-analyses of the data from an initial clinical investigation of 111 men, the subjects were divided into two subgroups: one group of 65 with symptoms but no impairment on the tests and one group of 46 with toxic encephalopathy (symptoms and test impairment). At least five years after the initial examination the subjects were asked to attend a re-examination that included a structured medical interview and a psychometric investigation. The results indicate that effects on the central nervous system persist even when exposure has ceased. In the group of 46 more men had stopped working and were receiving sickness or early retirement pensions. This group also had reduced activity levels with regard to everyday life, leisure activities, and education or training and more neuropsychiatric symptoms. There was no support for the view that a solvent induced toxic encephalopathy is a progressive disease comparable with presenile dementia such as Alzheimer's disease or Pick's disease. If a worker was removed from exposure when he presented symptoms without signs of impairment in intellectual function recovery was seen in most cases.
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| 28. |
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| 29. |
- Ekberg, Henrik, et al.
(author)
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Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation.
- 2009
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 9, s. 1876-1885
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Journal article (peer-reviewed)abstract
- The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low-doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow-up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow-up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow-up, renal function remained stable (mean change: -0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). The MMF and low-dose tacrolimus arm continued to have the highest GFR (68.6 +/- 23.8 ml/min vs. 65.9 +/- 26.2 ml/min in the standard-dose cyclosporine, 64.0 +/- 23.1 ml/min in the low-dose cyclosporine and 65.3 +/- 26.2 ml/min in the low-dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair-wise tests). The MMF and low-dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. In the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low-dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.
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| 30. |
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| 31. |
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| 32. |
- Ekberg, Jana, 1964, et al.
(author)
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A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-Risk Kidney Transplant Recipients
- 2022
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In: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:2, s. 259-269
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Journal article (peer-reviewed)abstract
- Introduction: Steroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft survival. In the SAILOR study, we investigated the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes on the current standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil (MMF). Methods: In this 2-year, multicenter, open-label trial, a total of 222 patients were randomized to receive either steroid avoidance protocol (tacrolimus/MMF/antithymocyte globulin [ATG] induction [n = 113]) or steroid maintenance protocol (tacrolimus/MMF/prednisolone/basiliximab-induction [n = 109]). Results: At 1 year, no significant differences were found between steroid avoidance and steroid maintenance arms in the incidence of PTDM, the primary end point (12.4% vs. 18.3%, respectively, P = 0.30, CI: 16.3–4.4), or in overall biopsy-proven rejections (15% vs. 13.8%, respectively, P = 0.85). At 2 years, the composite end point of freedom from acute rejection, graft loss, and death (81% vs. 85%, respectively, P = 0.4), kidney function, or adverse events was comparable between the 2 arms. Moreover, 63.9% of the patients in the steroid avoidance arm remained free from steroids at 2 years. Conclusion: The SAILOR study provides further evidence for the feasibility, safety, and efficacy of early steroid-free treatment at 2 years in immunologically low-risk kidney recipients with tacrolimus/MMF maintenance regimen. © 2021 International Society of Nephrology
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| 35. |
- Ekberg, N. R., et al.
(author)
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Smart Pen Exposes Missed Basal Insulin Injections and Reveals the Impact on Glycemic Control in Adults With Type 1 Diabetes
- 2024
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In: Journal of Diabetes Science and Technology. - : SAGE Publications. - 1932-2968. ; 18:1, s. 66-73
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Journal article (peer-reviewed)abstract
- Background: Adherence to basal insulin injections and the effects of missed basal insulin injections in adults with type 1 diabetes (T1D) were investigated using data from continuous glucose monitoring (CGM) and smart insulin pen devices in a real-world study. Methods: This was a post hoc analysis of a prospective, real-world study conducted in Sweden. Adults with T1D who were using CGM received a smart insulin pen device (NovoPen 6) for insulin injections. Missed basal insulin doses (≥40 hours between doses) were evaluated over 14-day periods, and the probability of missing basal insulin doses was estimated. Associations between missed basal insulin doses and glycemic outcomes were also explored. Results: Thirty-two patients with 4410 acceptable CGM days (315 14-day periods) were included. The number of missed basal insulin doses ranged from 0 to 4 over 315 14-day periods. The estimated probability of missing at least one basal insulin dose over any given 14-day period was 22% (95% confidence interval: 10%-40%). Missed basal insulin doses were significantly associated with higher mean glycemic levels, higher glucose management indicator, and lower time in range (70-180 mg/dL [3.9-10.0 mmol/L]). Similar results were observed when adjusted for missed bolus insulin doses; age and sex had no statistically significant effect on any glycemic parameter. Conclusions: This is the first study, based on accurate real-world injection data, to demonstrate the challenge of adherence to basal insulin injections in patients with T1D, and document that just one missed basal injection per week can result in clinically significant changes in glycemic control. © 2022 Diabetes Technology Society.
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| 36. |
- Ekberg, Olle, et al.
(author)
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An In Vitro Model for Studying Neuromuscular Transmission in the Mouse Pharynx.
- 2009
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In: Dysphagia. - : Springer Science and Business Media LLC. - 1432-0460 .- 0179-051X. ; 24, s. 32-39
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Journal article (peer-reviewed)abstract
- The muscles of the pharynx are controlled by networks of neurons under the control of specific regions in the brain stem, which have been fairly well studied. However, the transmission between these neurons and the pharyngeal muscles, at the motor end plates, is less well understood. Therefore, an in vitro model for the study of neuromuscular transmission in the pharyngeal muscle of the mouse was developed. Ring preparations from the inferior constrictor and the cricopharyngeus muscles were isolated and mounted for isometric force recording at physiologic temperature. Preparations from the diaphragm and the soleus muscles were examined in parallel. The muscles were stimulated at supramaximal voltage with short tetani at 100 Hz. Following direct stimulation of the muscle fibers, using a longer pulse duration, the rate of force development of the pharyngeal muscles was similar to that of the diaphragm and faster than that of the soleus muscle. By varying the duration of the stimulation pulses, conditions where the nerve-mediated activation contributed to a major extent of the contractile responses were identified. Gallamine completely inhibited the nerve-mediated responses. In separate experiments the dose dependence of gallamine inhibition was examined, showing similar sensitivity in the inferior pharyngeal constrictor compared to the diaphragm and soleus muscles. We conclude that reproducible contractile responses with an identifiable nerve-induced component can be obtained from the mouse inferior pharyngeal constrictor. The pharyngeal muscles have contractile characteristics similar to those of the faster diaphragm. The sensitivity to the neuromuscular blocking agent gallamine of the inferior pharyngeal constrictor was in the same concentration range as that of the diaphragm and soleus muscles.
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| 37. |
- Ekberg, Olle, et al.
(author)
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Dysphagia secondary to systemic diseases
- 2012
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In: Principles of Deglutition : A multidisciplinary Text for Swallowing and its Disorders - A multidisciplinary Text for Swallowing and its Disorders. - 9781461437932 ; , s. 485-492
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Book chapter (peer-reviewed)
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| 38. |
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| 39. |
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| 40. |
- Geist, A., et al.
(author)
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An overview of solvent extraction processes developed in Europe for advanced nuclear fuel recycling, part 1 - heterogeneous recycling
- 2021
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In: Separation Science and Technology. - : Informa UK Limited. - 1520-5754 .- 0149-6395. ; 56:11, s. 1866-1881
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Journal article (peer-reviewed)abstract
- The hydrometallurgical separation concepts for the heterogeneous recycling of irradiated nuclear fuel developed in Europe are presented and discussed. Most of these concepts were developed within European collaborative projects and involve solvent extraction processes separating trivalent minor actinides (with a focus on americium) from the raffinate solution from processes such as PUREX (Plutonium Uranium Reduction Extraction) or an evolution of PUREX. Depending on the process chemistry applied, process schemes each consisting of one, two or three solvent extraction cycles are required to obtain a pure americium product. The various solvent extraction processes are briefly introduced. The most suitable choices are selected, and the process schemes are compared to one another.
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| 41. |
- Geist, A., et al.
(author)
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The SACSESS Hydrometallurgy - Domain an Overview
- 2016
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In: Atalante 2016 International Conference on Nuclear Chemistry for Sustainable Fuel Cycles. - : Elsevier BV. - 1876-6196. ; 21, s. 218-222
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Conference paper (peer-reviewed)abstract
- The EURATOM FP7 project SACSESS (Safety of Actinide Separation Processes) is in continuity of a long line of preceding EURATOM projects. SACSESS is organised along four domains, one of them related to the development of hydrometallurgical (i.e. solvent extraction based) actinide separations processes. Within this domain, the most promising processes developed in previous projects are further developed, improving their technology readiness level (TRL) towards the point at which safe industrial implementation will be achievable.
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| 42. |
- Grinyo, Josep M., et al.
(author)
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The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony pharmacokinetic substudy
- 2009
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 24:7, s. 2269-2276
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Journal article (peer-reviewed)abstract
- Methods. A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal transplant patients received standard-dose cyclosporine, MMF 2 g/day and corticosteroids, or daclizumab induction, MMF 2 g/day and corticosteroids plus low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus. The area under the concentration-time curve (AUC(0-12)) of MPA and its metabolites between treatment groups was compared. Pharmacokinetic sampling was performed before MMF administration and at 20, 40, 75 min; 2, 3, 6, 8, 10 and 12 h post-dose on Day 7 and Months 1 and 3. Results. Compared with standard-dose cyclosporine, patients receiving low-dose tacrolimus or low-dose sirolimus had significantly higher AUC(0-12) values for MPA at Day 7 and Month 1 and for free MPA at Day 7, and significantly lower AUC(0-12) values for 7-O-MPA-glucuronide (MPAG) at Month 1 and for acyl-glucuronide at Months 1 and 3 (P < 0.05). AUC(0-12) of MPA and free MPA was significantly greater with low-dose tacrolimus and low-dose sirolimus than with low-dose cyclosporine in the first month (P < 0.05). The ratio of MPA to MPAG exposure was significantly higher in the three low-dose groups than in the standard-dose cyclosporine group (P < 0.05). Conclusions. Standard- and low-dose cyclosporine reduces the exposure of MPA and free MPA compared to low-dose tacrolimus or low-dose sirolimus in patients given the same dose of MMF.
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| 43. |
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| 44. |
- Hariz, Marwan I, et al.
(author)
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Multicentre European study of thalamic stimulation for parkinsonian tremor : a 6 year follow-up
- 2008
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In: Journal of neurology, neurosurgery and psychiatry. - : BMJ Group. - 1468-330X .- 0022-3050. ; 79:6, s. 694-699
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Journal article (peer-reviewed)abstract
- AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery.METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation.RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group.CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.
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| 45. |
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| 46. |
- Karlsson Sundbaum, Johanna, et al.
(author)
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Severe COVID-19 among patients with asthma and COPD: a report from the Swedish National Airway Register
- 2021
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In: Therapeutic Advances in Respiratory Disease. - : SAGE Publications. - 1753-4658 .- 1753-4666. ; 15
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Journal article (peer-reviewed)abstract
- Background: Patients with obstructive lung diseases may be at risk of hospitalization and/or death due to COVID-19. Aim: To estimate the frequency of severe COVID-19, and COVID-19-related mortality in a well-defined large population of patients with asthma and chronic inflammatory lung disease (COPD). Further to assess the frequency of asthma and COPD as registered comorbidities at discharge from hospital, and in death certificates. Methods: At the start of the pandemic, the Swedish National Airway Register (SNAR) included 271,404 patients with a physician diagnosis of asthma and/or COPD. In September 2020, after the first COVID-19 wave in Sweden, the database was linked with the National Patient Register (NPR), the Swedish Intensive Care Register and the Swedish Cause of Death Register, which all provide data about COVID-19 based on International Classification of Diseases (ICD-10) codes. Severe COVID-19 was defined as hospitalization and/or intensive care or death due to COVID-19. Results: Among patients in SNAR, 0.5% with asthma, and 1.2% with COPD were identified with severe COVID-19. Among patients < 18 years with asthma, only 0.02% were severely infected. Of hospitalized adults, 14% with asthma and 29% with COPD died. Further, of patients in SNAR, 56% with asthma and 81% with COPD were also registered in the NPR, while on death certificates the agreement was lower (asthma 24% and COPD 71%). Conclusion: The frequency of severe COVID-19 in asthma and COPD was relative low. Mortality for those hospitalized was double as high in COPD compared to asthma. Comorbid asthma and COPD were not always identified among patients with severe COVID-19.
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| 47. |
- Karlsson Sundbaum, Johanna, et al.
(author)
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Uncontrolled asthma predicts severe COVID-19: a report from the Swedish National Airway Register.
- 2022
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In: Therapeutic advances in respiratory disease. - : SAGE Publications. - 1753-4666 .- 1753-4658. ; 16
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Journal article (peer-reviewed)abstract
- Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19.A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19.Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR=1.04, 95% CI=1.03-1.04), male sex (1.42, 1.25-1.61), overweight (1.56, 1.27-1.91), obesity (2.12, 1.73-2.60), high-dose inhaled corticosteroids in combination with long-acting β-agonists (1.40, 1.22-1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25-1.75), uncontrolled asthma (1.64, 1.35-2.00), cardiovascular disease (1.20, 1.03-1.40), depression (1.47, 1.28-1.68), and diabetes (1.52, 1.29-1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47-0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death.Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.
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| 48. |
- Kasiske, Bertram L., et al.
(author)
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KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary
- 2010
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 77:4, s. 299-311
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Journal article (peer-reviewed)abstract
- The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere. Kidney International (2010) 77, 299-311; doi: 10.1038/ki.2009.377; published online 21 October 2009
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| 49. |
- Khalaf, K., et al.
(author)
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Geographical and sociodemographic differences in discontinuation of medication for Chronic Obstructive Pulmonary Disease - A Cross-Classified Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA)
- 2020
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In: Clinical Epidemiology. - 1179-1349. ; 12, s. 783-796
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Journal article (peer-reviewed)abstract
- Background: While discontinuation of COPD maintenance medication is a known problem, the proportion of patients with discontinuation and its geographical and sociodemographic distribution are so far unknown in Sweden. Therefore, we analyse this question by applying an innovative approach called multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). Patients and Methods: We analysed 49,019 patients categorized into 18 sociodemographic contexts and 21 counties of residence. All patients had a hospital COPD diagnosis and had been on inhaled maintenance medication during the 5 years before the study baseline in 2010. We defined "discontinuation" as the absolute lack of retrieval from a pharmacy of any inhaled maintenance medication during 2011. We performed a cross-classified MAIHDA and obtained the average proportion of discontinuation, as well as county and sociodemographic absolute risks, and compared them with a proposed benchmark value of 10%. We calculated the variance partition coefficient (VPC) and the area under the receiver operating characteristics curve (AUC) to quantify county and sociodemographic differences. To summarize the results, we used a framework with 15 scenarios defined by the size of the differences and the level of achievement in relation to the benchmark value. Results: Around 18% of COPD patients in Sweden discontinued maintenance medication, so the benchmark value was not achieved. There were very small county differences (VPC=0.35%, AUC=0.54). The sociodemographic differences were small (VPC=4.98%, AUC=0.57). Conclusion: Continuity of maintenance medication among COPD patients in Sweden could be improved by reducing the unjustifiably high prevalence of discontinuation. The very small county and small sociodemographic differences should motivate universal interventions across all counties and sociodemographic groups. Geographical analyses should be combined with sociodemographic analyses, and the cross-classified MAIHDA is an appropriate tool to assess health-care quality.
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| 50. |
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