| 1. |
- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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| 2. |
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| 3. |
- Schierbeck, S., et al.
(författare)
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Simulation and education National coverage of out-of-hospital cardiac arrests using automated external defibrillator-equipped drones-A geographical information system analysis
- 2021
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 163, s. 136-145
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early defibrillation is essential for increasing the chance of survival in out-of-hospital-cardiac-arrest (OHCA). Automated external defibrillator (AED)-equipped drones have a substantial potential to shorten times to defibrillation in OHCA patients. However, optimal locations for drone deployment are unknown. Our aims were to find areas of high incidence of OHCA on a national level for placement of AED-drones, and to quantify the number of drones needed to reach 50, 80, 90 and 100% of the target population within eight minutes. Methods: This is a retrospective observational study of OHCAs reported to the Swedish Registry for Cardiopulmonary Resuscitation between 2010-2018. Spatial analyses of optimal drone placement were performed using geographical information system (GIS)-analyses covering high-incidence areas (>100 OHCAs in 2010-2018) and response times. Results: 39,246 OHCAs were included. To reach all OHCAs in high-incidence areas with AEDs delivered by drone or ambulance within eight minutes, 61 drone systems would be needed, resulting in overall OHCA coverage of 58.2%, and median timesaving of 05:01 (min:sec) [IQR 03:22-06:19]. To reach 50% of the historically reported OHCAs in <8 min, 21 drone systems would be needed; for 80%, 366; for 90%, 784, and for 100%, 2408. Conclusions: At a national level, GIS-analyses can identify high incidence areas of OHCA and serve as tools to quantify the need of AED-equipped drones. Use of only a small number of drone systems can increase national coverage of OHCA substantially. Prospective real-life studies are needed to evaluate theoretically optimized suggestions for drone placement.
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| 4. |
- Alissa, S., et al.
(författare)
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Distribution of the adapted-NRTK correction data via VDES for the shipping navigation safety
- 2021
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Ingår i: Proceedings of the 34th International Technical Meeting of the Satellite Division of the Institute of Navigation, ION GNSS+ 2021. - : Institute of Navigation. - 9780936406299 ; , s. 521-534
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Konferensbidrag (refereegranskat)abstract
- In this study the maritime communication system VDES (VHF Data Exchange System) is proposed to distribute Network-RTK (NRTK) correction data to shipborne GNSS receivers in fairways, port areas, or inland water ways. The transport layer used for transmission of VDES messages (related to the standard IEC61162-450) is the UDP multicast protocol. This makes it possible to transmit the RTCM packages from the VDES transponder to the shipborne GNSS receivers as a UDP payload without any additional formatting. In order to minimize the impact on the overall VDES data capacity in a local service area, NRTK correction data shall at most occupy a single VDES slot with a net capacity of 650 bytes denoted Link ID 19. This is the fastest link in VDES. Update rates may vary but are preferably at 1Hz. However, depending on the number of visible satellites NRTK correction data size changes instantly and the data rate can therefore sometimes be in excess of 1000 byte/s per reference station to be distributed. In order to comply with the VDES requirements, the Lantmäteriet Adjustment Solution (LAS) for GNSS correction data adjustment was developed and is presented in this paper. The responsibility of this solution is to produce a correction data stream that complies with the bandwidth limitation of 650 bytes/s. To provide corrections for a potentially large number of users, dissemination is done by broadcasting corrections for a grid of VRSs. The proposed solution has therefore also the capability to combine several correction data streams from several Virtual Reference Stations (VRSs) into one single correction data stream. To reduce the required data rate, the LAS has the ability to filter streamed GNSS correction data in the RTCM3 MSM format constellation-wise, satellite-wise, and signal-wise. The objective is to achieve optimal performance in terms of accuracy for the ship's differential positioning solution, while at the same time adhering to constraints that might locally apply for individual transmitters. For this paper LAS was configured to interface with the SWEPOS to provide reference data to static and kinematic testing scenarios. The results presented here were obtained using RTK post-processing with RTKLib for a combination of GPS and Galileo multi-frequency observations. Results indicated that LAS solution can achieve robust positioning performance with decimeter-level accuracy which meet the requirements expected for the navigation safety at Sea. Adapted-NRTK correction data (LAS data) via VDES has the potential to be part of a world-wide standard VDES application for all vessels sailing under SOLAS and for ships that voluntarily uses VDES in the near future (inland, yachts, navies, leisure).
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| 5. |
- Behrendt, Lars, et al.
(författare)
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Life in the dark : far-red absorbing cyanobacteria extend photic zones deep into terrestrial caves
- 2020
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Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 22:3, s. 952-963
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Tidskriftsartikel (refereegranskat)abstract
- Chlorophyll (Chl) f and d are the most recently discovered chlorophylls, enabling cyanobacteria to harvest near-infrared radiation (NIR) at 700-780 nm for oxygenic photosynthesis. Little is known about the occurrence of these pigments in terrestrial habitats. Here, we provide first details on spectral photon irradiance within the photic zones of four terrestrial cave systems in concert with a detailed investigation of photopigmentation, light reflectance and microbial community composition. We frequently found Chl f and d along the photic zones of caves characterized by low light enriched in NIR and inhabited by cyanobacteria producing NIR-absorbing pigments. Surprisingly, deeper parts of caves still contained NIR, an effect likely attributable to the reflectance of specific wavelengths by the surface materials of cave walls. We argue that the stratification of microbial communities across the photic zones of cave entrances resembles the light-driven species distributions in forests and aquatic environments.
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| 7. |
- Claesson, A., et al.
(författare)
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Incidence and characteristics of drowning in Sweden during a 15-year period
- 2021
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Ingår i: Resuscitation. - : ELSEVIER IRELAND LTD. - 0300-9572 .- 1873-1570. ; 162, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Drowning is a global health problem and deeper knowledge about the extent and causes is of utmost importance for implementing preventative actions. The aim of this study was to describe the incidence and characteristics of drowning in Sweden over time, including both non-fatal and fatal cases. Methods: All cases identified as drowning (ICD-10 coding) at a national level in Sweden between 2003-2017 were collected. Three sources of data from the Swedish National Board of Health and Welfare were extracted via the Cause of Death Register and the National Patient Register. Results: Over 15 years, a total of 6609 cases occurred, resulting in an annual incidence of 4.66 per 100 000. The median age was 49 years (IQR 23-67) and 67% were males. Non-fatal drownings represented 51% (n = 3363), with an overall non-fatal to fatal ratio of 1:1, this being 8:1 for children (0-17 years of age). Non-fatal cases were more often female (36% vs. 30%; p < 0.001), younger 30 (IQR 10-56) vs. 60 (IQR: 45-72) (p < 0.001) and of unintentional nature (81% vs. 55%; p < 0.001). The overall incidence decreased over time from 5.6 to 4.1 per 100 000 (p < 0.001). The highest rate of 30-day survival was found in females 0-17 years (94%, 95% CI 91.1-95.5) and the lowest in males >66 years (28.7%, 95% CI 26.2-31.2). Although the incidence in children 0-4 years increased from 7.4 to 8.1 per 100 000 (p < 0.001), they demonstrated the highest non-fatal to fatal ratio (13:1). Conclusion: Drowning is declining but remains a consistent and underestimated public-health problem. Non-fatal drowning cases represent about half of the burden and characteristics differ from fatal drowning cases, being younger, more often female and of unintentional nature. Keywords: Drowning, Non-fatal, OHCA
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| 8. |
- Dutta, Uttama, et al.
(författare)
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Satellite selection in the context of network RTK for limited bandwidth applications
- 2021
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Ingår i: Proceedings of the 34th International Technical Meeting of the Satellite Division of the Institute of Navigation, ION GNSS+ 2021. - : Institute of Navigation. - 2331-5954. - 9780936406299 ; , s. 2474-2492
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Konferensbidrag (refereegranskat)abstract
- The increasing number of modernized GNSS signals and the availability of multi-constellation receivers are crucial for improvements of both precision and robustness of GNSS based positioning. However, the abundance of GNSS observations is not always useable as applications, using differential positioning or other techniques, may have limitations with respect to computational resources or communication bandwidth for reference data, and therefore require a qualified selection of a subset of observations for positioning. This paper is based on the work conducted in the project PREParE SHIPS funded by the European Union Agency for the Space Programme (EUSPA) on the specific application of Maritime Navigation using Network Real Time Kinematic (NRTK) and will focus on the satellite selection algorithms of the Prepare Ships dissemination solution. This study is motivated by data rate requirements and restrictions of the VDES dissemination solution developed in Prepare Ships. The restricted data rate for dissemination of RTK observations via VDES implies the need for a qualified pre-selection of satellite subsets to match the available bandwidth and the requirements of the positioning system. For this, multiple algorithms have been developed and tested in static and dynamic scenarios. Optimization techniques for height (for vertical position), two and three dimensions were examined. Different weighting schemes were used. During the evolution of the satellite selection study, it was concluded that it is necessary to retain satellites with the highest elevation as this will empirically improve integer ambiguity resolution for position fixing. Also fixing a minimum number of satellites for each constellation was required to enable a fair weightage to the different constellations used. Such algorithms should prove to be very useful for research on various Network RTK applications which require/prefer limited bandwidth such as for cadastral surveying and mapping, for airborne geo-referencing of aerial mapping data using Unmanned Aerial Vehicles (UAV) and on the road and sea for positioning and navigation of automated transport. Additionally, these algorithms could also be extended to consider satellite visibility in e.g. urban areas (i.e. urban canyons) by inclusion of true surface information for more robust GNSS positioning in automated transport applications [1]. This could either be for pre-evaluation or for dynamically considering spatial information. While this work is a part of PREParE SHIPS, it is also motivated by a more general applicability of the algorithms presented for other similar applications. RTK correction dissemination with limited bandwidth requirements is very promising for RTK research and therefore this study on optimized selection of satellite subsets is of vital importance and could tap multiple opportunities of huge potential such as those involving NRTK or combination of Precise Point Positioning with RTK. © 2021 Proceedings of the 34th International Technical Meeting of the Satellite Division of the Institute of Navigation, ION GNSS+ 2021.
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| 9. |
- Elfving, Hedvig, et al.
(författare)
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Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer
- 2021
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Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 151, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The small molecule inhibitors larotrectinib and entrectinib have recently been approved as cancer agnostic drugs in patients with tumours harbouring a rearrangement of the neurotrophic tropomyosin receptor kinase (NTRK). These oncogenic fusions are estimated to occur in 0.1-3 % of non-small cell lung cancers (NSCLC). Although molecular techniques are most reliable for fusion detection, immunohistochemical analysis is considered valuable for screening. Therefore, we evaluated the newly introduced diagnostic immunohistochemical assay (clone EPR17341) on a representative NSCLC cohort.Methods: Cancer tissue from 688 clinically and molecularly extensively annotated NSCLC patients were comprised on tissue microarrays and stained with the pan-TRK antibody clone EPR17341. Positive cases were further analysed with the TruSight Tumor 170 RNA assay (Illumina). Selected cases were also tested with a NanoString NTRK fusion assay. For 199 cases, NTRK RNA expression data were available from previous RNA sequencing analysis.Results: Altogether, staining patterns for 617 NSCLC cases were evaluable. Of these, four cases (0.6 %) demonstrated a strong diffuse cytoplasmic and membranous staining, and seven cases a moderate staining (1.1 %). NanoString or TST170-analysis could not confirm an NTRK fusion in any of the IHC positive cases, or any of the cases with high mRNA levels. In the four cases with strong staining intensity in the tissue microarray, whole section staining revealed marked heterogeneity of NTRK protein expression.Conclusion: The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay will result in a small number of false positive cases. This should be considered when the assay is applied as a screening tool in clinical diagnostics.
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