Point-of-care ultrasound induced changes in management of unselected patients in the emergency department - a prospective single-blinded observational trial

Background Point-of-Care ultrasound (POCUS) changes the management in specific groups of patients in the Emergency Department (ED). It seems intuitive that POCUS holds an unexploited potential on a wide variety of patients. However, little is known about the effect of ultrasound on the broad spectrum of unselected patients in the ED. This study aimed to identify the effect on the clinical management if POCUS was applied on unselected patients. Secondarily the study aimed to identify predictors of ultrasound changing management. Methods This study was a blinded observational single center trial. A basic whole body POCUS protocol was performed in extension to the physical examination. The blinded treating physicians were interviewed about the presumptive diagnosis and plan for the patient. Subsequently the physicians were unblinded to the POCUS results and asked to choose between five options regarding the benefit from POCUS results. Results A total of 403 patients were enrolled in this study. The treating physicians regarded POCUS examinations influence on the diagnostic workup or treatment as following: 1) No new information: 249 (61.8%), 2) No further action: 45 (11.2%), 3) Further diagnostic workup needed: 52 (12.9%), 4) Presumptive diagnosis confirmed 38 (9.4%), and 5) Immediate treatment needed: 19 (4.7%). Predictors of beneficial ultrasound were: (a) triage > 1, (b) patient comorbidities (cardiac disease, hypertension or lung disease), or (c) patients presenting with abdominal pain, dyspnea, or syncope. Conclusion POCUS was found to be potentially beneficial in 27.0% of all patients. High triage score, known cardiac disease, hypertension, pulmonary diseases, a clinical presentation with abdominal pain, dyspnea, or syncope are predictors of this. Future research should focus on patient-important outcomes when applying POCUS on these patients. Trial registration The trail was registered prior to patient inclusion with the Danish Data Protection Agency (https://www.datatilsynet.dk/ Case no: 1–16–02-603-14) and Clinical Trials (www.clinicaltrials.gov/ Protocol ID: DNVK1305018)

Trauma facilities in Denmark - a nationwide cross-sectional benchmark study of facilities and trauma care organisation

Background Trauma is a leading cause of death among adults aged < 44 years, and optimal care is a challenge. Evidence supports the centralization of trauma facilities and the use multidisciplinary trauma teams. Because knowledge is sparse on the existing distribution of trauma facilities and the organisation of trauma care in Denmark, the aim of this study was to identify all Danish facilities that care for traumatized patients and to investigate the diversity in organization of trauma management. Methods We conducted a systematic observational cross-sectional study. First, all hospitals in Denmark were identified via online services and clarifying phone calls to each facility. Second, all trauma care manuals on all facilities that receive traumatized patients were gathered. Third, anesthesiologists and orthopedic surgeons on call at all trauma facilities were contacted via telephone for structured interviews. Results A total of 22 facilities in Denmark were found to receive traumatized patients. All facilities used a trauma care manual and all had a multidisciplinary trauma team. The study found three different trauma team activation criteria and nine different compositions of teams who participate in trauma care. Training was heterogeneous and, beyond the major trauma centers, databases were only maintained in a few facilities. Conclusion The study established an inventory of the existing Danish facilities that receive traumatized patients. The trauma team activation criteria and the trauma teams were heterogeneous in both size and composition. A national database for traumatized patients, research on nationwide trauma team activation criteria, and team composition guidelines are all called for

Efficacy and safety of emapalumab in macrophage activation syndrome

OBJECTIVES: Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria. METHODS: We studied emapalumab, a human anti-IFNγ antibody, administered with background glucocorticoids, in a prospective single-arm trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids, with or without anakinra and/or ciclosporin. The study foresaw 4-week treatment that could be shortened or prolonged based on investigator's assessment of response. Patients entered a long-term (12 months) follow-up study. RESULTS: Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFNγ activity, demonstrated by a prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, MAS remission was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed. CONCLUSIONS: Neutralisation of IFNγ with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids. Screening for viral infections should be performed, particularly for cytomegalovirus. TRIAL REGISTRATION NUMBER: NCT02069899 and NCT03311854

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Staphylococcus aureus Bacteremia in Children of Rural Areas of The Gambia, 2008–2015

Staphylococcus aureus bacteremia is a substantial cause of childhood disease and death, but few studies have described its epidemiology in developing countries. Using a population-based surveillance system for pneumonia, sepsis, and meningitis, we estimated S. aureus bacteremia incidence and the case-fatality ratio in children <5 years of age in 2 regions in the eastern part of The Gambia during 2008–2015. Among 33,060 children with suspected pneumonia, sepsis, or meningitis, we performed blood culture for 27,851; of 1,130 patients with bacteremia, 198 (17.5%) were positive for S. aureus. S. aureus bacteremia incidence was 78 (95% CI 67–91) cases/100,000 person-years in children <5 years of age and 2,080 (95% CI 1,621–2,627) cases/100,000 person-years in neonates. Incidence did not change after introduction of the pneumococcal conjugate vaccine. The case-fatality ratio was 14.1% (95% CI 9.6%–19.8%). Interventions are needed to reduce the S. aureus bacteremia burden in The Gambia, particularly among neonates

Functional Analysis of Ficolin-3 Mediated Complement Activation

The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway

Climate change in the Baltic Sea region : a summary

Based on the Baltic Earth Assessment Reports of this thematic issue in Earth System Dynamics and recent peer-reviewed literature, current knowledge of the effects of global warming on past and future changes in climate of the Baltic Sea region is summarised and assessed. The study is an update of the Second Assessment of Climate Change (BACC II) published in 2015 and focuses on the atmosphere, land, cryosphere, ocean, sediments, and the terrestrial and marine biosphere. Based on the summaries of the recent knowledge gained in palaeo-, historical, and future regional climate research, we find that the main conclusions from earlier assessments still remain valid. However, new long-term, homogenous observational records, for example, for Scandinavian glacier inventories, sea-level-driven saltwater inflows, so-called Major Baltic Inflows, and phytoplankton species distribution, and new scenario simulations with improved models, for example, for glaciers, lake ice, and marine food web, have become available. In many cases, uncertainties can now be better estimated than before because more models were included in the ensembles, especially for the Baltic Sea. With the help of coupled models, feedbacks between several components of the Earth system have been studied, and multiple driver studies were performed, e.g. projections of the food web that include fisheries, eutrophication, and climate change. New datasets and projections have led to a revised understanding of changes in some variables such as salinity. Furthermore, it has become evident that natural variability, in particular for the ocean on multidecadal timescales, is greater than previously estimated, challenging our ability to detect observed and projected changes in climate. In this context, the first palaeoclimate simulations regionalised for the Baltic Sea region are instructive. Hence, estimated uncertainties for the projections of many variables increased. In addition to the well-known influence of the North Atlantic Oscillation, it was found that also other low-frequency modes of internal variability, such as the Atlantic Multidecadal Variability, have profound effects on the climate of the Baltic Sea region. Challenges were also identified, such as the systematic discrepancy between future cloudiness trends in global and regional models and the difficulty of confidently attributing large observed changes in marine ecosystems to climate change. Finally, we compare our results with other coastal sea assessments, such as the North Sea Region Climate Change Assessment (NOSCCA), and find that the effects of climate change on the Baltic Sea differ from those on the North Sea, since Baltic Sea oceanography and ecosystems are very different from other coastal seas such as the North Sea. While the North Sea dynamics are dominated by tides, the Baltic Sea is characterised by brackish water, a perennial vertical stratification in the southern subbasins, and a seasonal sea ice cover in the northern subbasins.Peer reviewe