| 1. |
- Camm, A John, et al.
(author)
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XANTUS : a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation.
- 2016
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 37:14, s. 1145-53
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Journal article (peer-reviewed)abstract
- AIMS: Although non-vitamin K antagonist oral anticoagulants are recommended for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) based on clinical trial results, there is a need for safety and efficacy data from unselected patients in everyday clinical practice. XANTUS investigated the safety and efficacy of the Factor Xa inhibitor rivaroxaban in routine clinical use in the NVAF setting.METHODS AND RESULTS: Consecutive consenting patients with NVAF newly started on rivaroxaban were eligible and were followed up at ∼3-month intervals for 1 year, or for at least 30 days after permanent discontinuation. All adverse events (AEs) were recorded as AEs or serious AEs; major outcomes (including major bleeding, symptomatic thromboembolic events [stroke, systemic embolism, transient ischaemic attack, and myocardial infarction], and all-cause death) were centrally adjudicated. There were 6784 patients treated with rivaroxaban at 311 centres in Europe, Israel, and Canada. Mean patient age was 71.5 years (range 19-99), 41% were female, and 9.4% had documented severe or moderate renal impairment (creatinine clearance <50 mL/min). The mean CHADS2 and CHA2DS2-VASc scores were 2.0 and 3.4, respectively; 859 (12.7%) patients had a CHA2DS2-VASc score of 0 or 1. The mean treatment duration was 329 days. Treatment-emergent major bleeding occurred in 128 patients (2.1 events per 100 patient-years), 118 (1.9 events per 100 patient-years) died, and 43 (0.7 events per 100 patient-years) suffered a stroke.CONCLUSION: XANTUS is the first international, prospective, observational study to describe the use of rivaroxaban in a broad NVAF patient population. Rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice.TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT01606995.
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| 2. |
- Cvijovic, Marija, 1977, et al.
(author)
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Strategies for structuring interdisciplinary education in systems biology: An European perspective
- 2016
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In: npj Systems Biology and Applications. - : Springer Science and Business Media LLC. - 2056-7189. ; 2
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Journal article (peer-reviewed)abstract
- Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master’s programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii) a description of possible career paths for students who undergo such an education, (iv) conditions that should improve the recruitment of students to such programmes and (v) mechanisms for collaboration and excellence spreading among education professionals. With the growing interest of industry in applying Systems Biology approaches in their fields, a concerted action between academia and industry is needed to build this expertise. Here we present a reflection of the European situation and expertise, where most of the challenges we discuss are universal, anticipating that our suggestions will be useful internationally. We believe that one of the overriding goals of any Systems Biology education should be a student’s ability to phrase and communicate research questions in such a manner that they can be solved by the integration of experiments and modelling, as well as to communicate and collaborate productively across different experimental and theoretical disciplines in research and development.
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| 3. |
- Hess Engström, Andrea, et al.
(author)
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Internet-based Treatment for Vulvodynia (EMBLA) – A Randomized Controlled Study
- 2022
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In: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 19:2, s. 319-330
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Journal article (peer-reviewed)abstract
- Background: Internet-based ACT (Acceptance and commitment therapy) treatment may improve accessibility and reduce stigma related to seeking health care, but there are a lack of studies investigating internet-based treatment using ACT principles for women with vulvodynia.Aim: The aim of this study was to investigate the effects of an internet-based treatment of pain during intercourse for women with provoked vulvodynia compared with no intervention during the waiting period before clinical treatment.Methods: A multicenter randomized controlled trial was conducted during 2016 to 2020, in which 99 participants were included. Participants were randomized to either a 6 week guided internet-based treatment using ACT principles or usual care. Data were collected at baseline, 6 weeks after baseline, and approximately 10 months after baseline.Outcomes: Pain-related (pain during intercourse, tampon test, impact of pain on sexual function) and pain behavior-related outcomes (attempts at intercourse, sexual activities besides intercourse, willingness to perform the tampon test, chronic pain acceptance questionnaire) were used as outcomes.Results: Treatment was efficacious in what concerns pain during intercourse and pain acceptance. Less pain during intercourse among women in the intervention group was observed at both post-treatment (primary endpoint, P = .01, Cohen's d = 1.4, 95% CI = 0.33, 2.4), and follow-up (P = .04). Absolut mean difference between groups for pain during intercourse at post-treatment was -2.84, 95 % CI = -4.91, -0.78), and -1.58 at follow-up, 95 % CI = -3.17, 0.02), where the intervention group rated less pain than controls. No differences between groups over time were found for tampon test measures or impact of pain on sexual function. There was a significant difference between groups at all timepoints indicating fewer attempts at intercourse among participants in the intervention group. At post-treatment, women who underwent internet-based treatment reported higher pain acceptance and a rise in activity engagement compared with the control group.Clinical Implications: There is an indication that internet-based treatment could be incorporated into clinical practice as a complement to clinical treatment.Strengths & Limitations: Study strengths included using several forms of recruitment and an intervention built by different professions with long experience of treating patients with vulvodynia. High dropout rate was a limitation of this study.Conclusion: Internet-based treatment may have an impact on pain during intercourse and positive effects on pain acceptance. However, conclusions must be drawn with caution due to the small sample size.
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| 4. |
- Hess Engström, Andrea, et al.
(author)
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Internet-based treatment for vulvodynia (EMBLA)-Study protocol for a randomised controlled study
- 2021
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In: Internet Interventions. - : Elsevier. - 2214-7829. ; 25
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Journal article (peer-reviewed)abstract
- Background: Vulvodynia is defined as vulvar pain for at least 3 months without a clear cause. To the best of our knowledge, there are no trials investigating the effects of internet treatment using CBT (Cognitive behavioural therapy) treatment with Acceptance and Commitment Therapy (ACT) components for women with vulvodynia. The aim of this study is to examine the effects of such a guided internet-based intervention on provoked vulvar pain during the waiting period before clinical treatment. Methods: We will randomise 52 patients to either guided internet-based intervention with CBT with (ACT) components or no intervention during the waiting period for treatment as usual. Online assessments are conducted at baseline, posttreatment, and at follow-up after 9 months. The primary outcome measure is provoked vulvar pain. Secondary outcomes are depression, anxiety, sexual function, and quality of life. Linear-mixed effect models will be used to assess the effect of the internet-based intervention on vulvar pain, pain acceptance, depression, anxiety, sexual function, and quality of life over time, by applying the intention-to-treat approach. Continuous data will be analysed with general linear models using intention-to-treat and also per protocol approaches to assess the effects of the intervention at different time points. Ordinal and binary data will be analysed with Mann Whitney's test, Fischer's exact test and multivariate logistic regression, respectively. Discussion: As a randomised controlled trial with short- and long-term follow-up points, the EMBLA study intends to provide a novel and better understanding regarding the treatment of vulvodynia and the role of internet-based treatment as a complement to standard care for women suffering from vulvodynia. The effects of vulvodynia on pain, sexual function, quality of life, depression, and anxiety are investigated. The study's results are expected to be of value in the planning of clinical care in the medical area. High dropout rates and technical difficulties associated with using the platform are common in similar studies. Trial registration number: NCT02809612
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| 5. |
- Kälsch, Hagen, et al.
(author)
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Are air pollution and traffic noise independently associated with atherosclerosis : the Heinz Nixdorf Recall Study
- 2014
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:13, s. 853-60
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Journal article (peer-reviewed)abstract
- AIMS: Living close to high traffic has been linked to subclinical atherosclerosis, however it is not clear, whether fine particulate matter (PM) air pollution or noise, two important traffic-related exposures, are responsible for the association. We investigate the independent associations of long-term exposure to fine PM and road traffic noise with thoracic aortic calcification (TAC), a reliable measure of subclinical atherosclerosis.METHODS AND RESULTS: We used baseline data (2000-2003) from the German Heinz Nixdorf Recall Study, a population-based cohort of 4814 randomly selected participants. We assessed residential long-term exposure to PM with a chemistry transport model, and to road traffic noise using façade levels from noise models as weighted 24 h mean noise (Lden) and night-time noise (Lnight). Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. We used multiple linear regression to estimate associations of environmental exposures with ln(TAC+1), adjusting for each other, individual, and neighbourhood characteristics. In 4238 participants (mean age 60 years, 49.9% male), PM2.5 (aerodynamic diameter ≤2.5 µm) and Lnight are both associated with an increasing TAC-burden of 18.1% (95% CI: 6.6; 30.9%) per 2.4 µg/m(3) PM2.5 and 3.9% (95% CI 0.0; 8.0%) per 5dB(A) Lnight, respectively, in the full model and after mutual adjustment. We did not observe effect measure modification of the PM2.5 association by Lnight or vice versa.CONCLUSION: Long-term exposure to fine PM and night-time traffic noise are both independently associated with subclinical atherosclerosis and may both contribute to the association of traffic proximity with atherosclerosis.
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| 6. |
- Neely, G Gregory, et al.
(author)
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A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
- 2010
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In: Cell. - : Elsevier Science B.V., Amsterdam.. - 0092-8674 .- 1097-4172. ; 143:4, s. 628-638
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Journal article (peer-reviewed)abstract
- Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
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| 7. |
- Oefner, Carolin M., et al.
(author)
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Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs
- 2012
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 129:6, s. 1647-1647
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Journal article (peer-reviewed)abstract
- Background: Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T-and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. Objective: It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction. Methods: We administered chicken ovalbumin (OVA) with or without costimulus to mice and analyzed OVA-reactive IgG Fc glycosylation. The anti-inflammatory function of differentially glycosylated anti-OVA IgGs was further investigated in studies with dendritic cell cultures and in an in vivo model of allergic airway disease. Additionally, we analyzed the Fc glycosylation pattern of birch pollen-reactive serum IgGs after successful allergen-specific immunotherapy in patients. Results: Stimulation with TD antigens under inflammatory conditions induces plasma cells expressing low levels of alpha 2,6-sialyltransferase and producing desialylated IgGs. In contrast, plasma cells induced on tolerance induction did not downregulate alpha 2,6-sialyltransferase expression and secreted immunosuppressive sialylated IgGs that were sufficient to block antigen-specific T- and B-cell responses, dendritic cell maturation, and allergic airway inflammation. Importantly, successful specific immunotherapy in allergic patients also induced sialylated allergen-specific IgGs. Conclusions: Our data show a novel antigen-specific immunoregulatory mechanism mediated by anti-inflammatory sialylated IgGs that are formed on TD tolerance induction. These findings might help to develop novel antigen-specific therapies for the treatment of allergy and autoimmunity. (J Allergy Clin Immunol 2012;129:1647-55.)
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| 8. |
- Viirman, Frida, et al.
(author)
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Negative childbirth experience in relation to mode of birth and events during labour: a mixed method study
- 2023
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In: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier. - 0301-2115 .- 1872-7654. ; 282, s. 146-154
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Journal article (peer-reviewed)abstract
- Objective: To explore descriptions of negative childbirth experience in relation to mode of birth and events during labour.Design: A descriptive study using a convergent mixed methods design. Written responses to open-ended online questions regarding negative childbirth experience were explored using qualitative content analysis. Generated sub-themes were quantified, and stratified on mode of birth and events during labour.Participants and setting: 112 women with low ratings of overall childbirth experience, participating in a randomised controlled trial evaluating internet-based cognitive behavioural therapy in Sweden. Qualitative data were collected before randomisation, three months postpartum.Results: Four sub-themes emerged from the qualitative analysis: Experiencing fear-based emotions, Experiencing physical distress, Being affected by caregivers’ and partner’s behaviour and Being affected by bad facilities and poor organisation. Only small differences were found when stratifying sub-themes on mode of birth and events during labour. Regardless of mode of birth and events during labour, the childbirth experience was dominated by fear-based emotions.Key conclusions and implications for practice: Mixed-methods analyses demonstrate the challenges in understanding negative childbirth experience in relation to mode of birth and specific events during labour, with results clearly showing the multifaceted nature of this concept. The central role of fear in relation to negative childbirth experience should be considered when designing support during and after labour, to prevent adverse effects of the childbirth experience.
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