| 1. |
- Baunwall, Simon Mark Dahl, et al.
(författare)
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The use of Faecal Microbiota Transplantation (FMT) in Europe : A Europe-wide survey
- 2021
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.Methods: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.Findings: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.Interpretation: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.Funding: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).
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| 2. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 3. |
- Bjurström, Martin F., et al.
(författare)
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Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study
- 2024
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Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRandomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels.MethodsIn this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables.ResultsIn total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results.ConclusionsImplementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.
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| 4. |
- Ernstsen, Siw L., et al.
(författare)
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Antenatal intravenous immunoglobulins in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia : comparison of neonatal outcome in treated and nontreated pregnancies
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378. ; 227:3, s. 1-506
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maternal alloantibodies to human platelet antigen-1a can cause severe intracranial hemorrhage in a fetus or newborn. Although never evaluated in placebo-controlled clinical trials, most Western countries use off-label weekly administration of high-dosage intravenous immunoglobulin in all pregnant women with an obstetrical history of fetal and neonatal alloimmune thrombocytopenia. In Norway, antenatal intravenous immunoglobulin is only recommended in pregnancies wherein a previous child had intracranial hemorrhage (high-risk) and is generally not given in other human platelet antigen-1a alloimmunized pregnancies (low-risk). Objective: To compare the frequency of anti-human platelet antigen-1a-induced intracranial hemorrhage in pregnancies at risk treated with intravenous immunoglobulin vs pregnancies not receiving this treatment as a part of a different management program. Study Design: This was a retrospective comparative study where the neonatal outcomes of 71 untreated human platelet antigen-1a-alloimmunized pregnancies in Norway during a 20-year period was compared with 403 intravenous-immunoglobulin-treated pregnancies identified through a recent systematic review. We stratified analyses on the basis of whether the mothers belonged to high- or low-risk pregnancies. Therefore, only women who previously had a child with fetal and neonatal alloimmune thrombocytopenia were included. Results: Two neonates with brain bleeds were identified from 313 treated low-risk pregnancies (0.6%; 95% confidence interval, 0.2–2.3). There were no neonates born with intracranial hemorrhage of 64 nontreated, low-risk mothers (0.0%; 95% confidence interval, 0.0–5.7). Thus, no significant difference was observed in the neonatal outcome between immunoglobulin-treated and untreated low-risk pregnancies. Among high-risk mothers, 5 of 90 neonates from treated pregnancies were diagnosed with intracranial hemorrhage (5.6%; 95% confidence interval, 2.4–12.4) compared with 2 of 7 neonates from nontreated pregnancies (29%; 95% confidence interval, 8.2–64.1; P=.08). Conclusion: The most reliable data hitherto for the evaluation of intravenous immunoglobulins treatment in low-risk pregnancies is shown herein. We did not find evidence that omitting antenatal intravenous immunoglobulin treatment in low-risk pregnancies increases the risk of neonatal intracranial hemorrhage.
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| 5. |
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| 6. |
- Fejrskov, Anja, et al.
(författare)
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Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease : protocol for the Nordic inception cohort study (NORDTREAT)
- 2024
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Ingår i: BMJ Open. - : BioMed Central (BMC). - 2044-6055. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.
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| 7. |
- Geisen, Christof, et al.
(författare)
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An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia : a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study
- 2023
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 21:4, s. 838-849
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT. Objectives: To investigate whether a single dose of anti–HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a–negative participants as compared with placebo. Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a– and HLA-A2–negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo. Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment–emergent adverse events were possibly related to treatment, both in RLYB211–treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks. Conclusion: These data support the hypothesis that anti–HPA-1a could be used as prophylaxis in women at risk of having an FNAIT–affected pregnancy.
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| 8. |
- Holm, Karin, et al.
(författare)
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Convalescence plasma treatment of COVID-19 : results from a prematurely terminated randomized controlled open-label study in Southern Sweden
- 2021
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Ingår i: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19.Results: Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups.
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| 9. |
- Ihlen, Øyvind, et al.
(författare)
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Transparency beyond information disclosure : strategies of the Scandinavian public health authorities during the COVID-19 pandemic
- 2022
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Ingår i: Journal of Risk Research. - : Taylor & Francis. - 1366-9877 .- 1466-4461. ; 25:10, s. 1176-1189
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Tidskriftsartikel (refereegranskat)abstract
- The concept of transparency has been problematized in risk research. This exploratory study contributes to the risk literature by considering an established three-dimensional transparency framework (information substantiality, accountability, and participation) and discussing the opportunities for and challenges to risk communication in relation to the framework. Furthermore, we examine the strategies of Scandinavian health authorities during the COVID-19 pandemic and the different levels of public trust in these authorities. In general, Norwegian authorities received higher levels of trust than their Swedish and Danish counterparts. We argue that this was partly due to differences in transparency management. Our findings support the importance of the three transparency dimensions and indicate that transparency regarding uncertainties positively impacts levels of trust.
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| 10. |
- Kjær, Kurt H., et al.
(författare)
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Glacier response to the Little Ice Age during the Neoglacial cooling in Greenland
- 2022
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Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 227
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Tidskriftsartikel (refereegranskat)abstract
- In the Northern Hemisphere, an insolation driven Early to Middle Holocene Thermal Maximum was followed by a Neoglacial cooling that culminated during the Little Ice Age (LIA). Here, we review the glacier response to this Neoglacial cooling in Greenland. Changes in the ice margins of outlet glaciers from the Greenland Ice Sheet as well as local glaciers and ice caps are synthesized Greenland-wide. In addition, we compare temperature reconstructions from ice cores, elevation changes of the ice sheet across Greenland and oceanographic reconstructions from marine sediment cores over the past 5,000 years. The data are derived from a comprehensive review of the literature supplemented with unpublished reports. Our review provides a synthesis of the sensitivity of the Greenland ice margins and their variability, which is critical to understanding how Neoglacial glacier activity was interrupted by the current anthropogenic warming. We have reconstructed three distinct periods of glacier expansion from our compilation: two older Neoglacial advances at 2,500 – 1,700 yrs. BP (Before Present = 1950 CE, Common Era) and 1,250 – 950 yrs. BP; followed by a general advance during the younger Neoglacial between 700-50 yrs. BP, which represents the LIA. There is still insufficient data to outline the detailed spatio-temporal relationships between these periods of glacier expansion. Many glaciers advanced early in the Neoglacial and persisted in close proximity to their present-day position until the end of the LIA. Thus, the LIA response to Northern Hemisphere cooling must be seen within the wider context of the entire Neoglacial period of the past 5,000 years. Ice expansion appears to be closely linked to changes in ice sheet elevation, accumulation, and temperature as well as surface-water cooling in the surrounding oceans. At least for the two youngest Neoglacial advances, volcanic forcing triggering a sea-ice /ocean feedback, could explain their initiation. There are probably several LIA glacier fluctuations since the first culmination close to 1250 CE (Common Era) and available data suggests ice culminations in the 1400s, early to mid-1700s and early to mid-1800s CE. The last LIA maxima lasted until the present deglaciation commenced around 50 yrs. BP (1900 CE). The constraints provided here on the timing and magnitude of LIA glacier fluctuations delivers a more realistic background validation for modelling future ice sheet stability.
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