Knut Fredriksen

CPR knowledge and attitude to performing bystander CPR among secondary school students in Norway

BACKGROUND Early bystander cardiopulmonary resuscitation (CPR) is essential for survival from out-of-hospital cardiac arrest (OHCA). Young people are potentially important bystander CPR providers, as basic life support (BLS) training can be distributed widely as part of the school curriculum. METHODS Questionnaires were distributed to nine secondary schools in North Norway, and 376 respondents (age 16-19 years) were included. The completed questionnaires were statistically analysed to assess CPR knowledge and attitude to performing bystander CPR. RESULTS Theoretical knowledge of handling an apparently unresponsive adult person was high, and 90% knew the national medical emergency telephone number (113). The majority (83%) was willing to perform bystander CPR in a given situation with cardiac arrest. However, when presented with realistic hypothetical cardiac arrest scenarios, the option to provide full BLS was less frequently chosen, to e.g. a family member (74%), a child (67%) or an intravenous drug user (18%). Students with BLS training in school and self-reported confidence in their own BLS skills reported stronger willingness to perform BLS. 8% had personally witnessed a cardiac arrest, and among these 16% had performed full BLS. Most students (86%) supported mandatory BLS training in school, and three out of four wanted to receive additional training. CONCLUSION Young Norwegians are motivated to perform bystander CPR, but barriers are still seen when more detailed cardiac arrest scenarios are presented. By providing students with good quality BLS training in school, the upcoming generation in Norway may strengthen the first part of the chain of survival in OHCA.

Antibodies to dsDNA are Produced During Primary BK Virus Infection in Man, Indicating that Anti‐dsDNA Antibodies may be Related to Virus Replication In Vivo

Experimental immunizations with both the Polyomavirus BK and with the isolated viral genomic dsDNA regularly induce antibodies with a relative affinity for BK virus dsDNA. In the present study we demonstrate that the anti‐dsDNA responses to BK virus in experimental animals also appear during natural BK virus infection in man. Fifty‐nine children were examined over time for serological signs of primary BK virus infection. Of eight children found to undergo primary infection with BK virus, anti‐BK dsDNA antibodies appeared in all. In 4 of the 8 patients the antibodies cross‐reacted significantly with mammalian dsDNA, and weak cross‐reactions were also noted in at least three other patients. The antibodies resembled those induced in the experimental model with regard to their relative affinity for BK dsDNA. In contrast, most, but not all, anti‐dsDNA antibodies from 10 SLE patients cross‐reacted extensively with dsDNA from viral and mammalian origin. Thus, a dsDNA virus like BK virus may provoke immunological intolerance to dsDNA, but, with qualities different from those produced during SLE. The present observations demonstrate that induction of anti‐dsDNA antibodies is not restricted to experimental immunization of animals, but does also take place in humans during naturally acquired BK virus infection. The relevance of this model for the spontaneous production of anti‐dsDNA antibodies is discussed.

Antibodies to Eukaryotic, including Autologous, Native DNA are Produced during BK Virus Infection, but not after Immunization with Non-Infectious BK DNA

The contemporary view concerning the origin of anti‐dsDNA antibodies is that eukaryotic dsDNA is not immunogenic. Results presented here, however, show (1) that inoculation of rabbits with BK virus elicits antibodies to eukaryotic, including autologous, dsDNA. (2) that the transition from a non‐immunogenic to an immunogenic state of autologous dsDNA depends on productive infection with BK virus, and (3) that inoculation with protein‐free circular BK dsDNA initiates both infection in vivo and production of antibodies to autologous dsDNA. Non‐infectious linearized BK dsDNA did not elicit any anti‐dsDNA antibodies, while the same DNA molecule, when complexed with methylated bovine serum albumin, elicited anti‐dsDNA antibodies solely recognizing BK dsDNA. Neither of the two linearized BK dsDNA preparations initiated infection. Using two different techniques, we could demonstrate that two separate sets of anti‐dsDNA antibodies were produced during viral infection; one recognizing BK dsDNA, and the other recognizing autologous dsDNA. Thus, in contrast to previous assumptions, autologous dsDNA may be immunogenic. Based on the present results, we propose that autologous dsDNA can be rendered immunogenic through complex formation with viral DNA binding protein(s) such as the structural protein VP1 or the tumour antigen T. Such DNA protein complexes may bypass a pulative T‐cell tolerance to autologous dsDNA.

Evaluation of a university hospital trauma team activation protocol

BackgroundAdmission with a multidisciplinary trauma team may be vital for the severely injured patient, as this facilitates rapid diagnosis and treatment. On the other hand, patients with minor injuries do not need the trauma team for adequate care. Correct triage is important for optimal resource utilization. The aim of the study was to evaluate our criteria for activating the trauma team, and identify suboptimal criteria that might be changed in the interest of precision.MethodsThe study is an observational, retrospective cohort-study. All patients admitted with the trauma team (n = 382), all severely injured (Injury Severity Score (ISS) >15) (n = 161), and all undergoing an emergency procedure aimed at counteracting compromised airways, respiration or circulation at our hospital (n = 142) during 2006-2007 were included. Data were recorded from the admission records and the electronic patient records. The trauma team activation protocol was evaluated against the occurrence of severe injury and the occurrence of emergency procedures.ResultsA total of 441 patients were included. The overtriage was 71% and undertriage 32% when evaluating against ISS >15 as the standard of reference. When occurrence of emergency procedures was held as the standard of standard of reference, the over- and undertriage was 71% and 21%, respectively. Mechanism of injury-criteria for trauma team activation contributed the most to overtriage. The emergency procedures performed were mostly endotracheal intubation and external fixation of fractures. Less than 3% needed haemostatic laparotomy or thoracotomy. Approximately 2/3 of the overtriage represented isolated head or cervical spine injuries, and/or interhospital transfers.ConclusionsThe over- and undertriage of our protocol are both too high. To decrease overtriage we suggest omissions and modifications of some of the criteria. To decrease undertriage, transferred patients and patients with head injuries should be more thoroughly assessed against the trauma team activation criteria.

Molecular Analyses of Anti-DNA Antibodies Induced by Polyomavirus BK in BALB/c Mice

In the present experiments, two groups of BALB/c mice (five individuals in each group) were hyperimmunized through four consecutive immunizations with either BK virus (Group 1) or BK dsDNA complexed with methylated BSA (Group 2). All immune sera taken after the fourth immunization from both groups reacted strongly with polyomavirus BK dsDNA as well as with calf thymus dsDNA, and all sera contained antibodies that bound in the Crithidia luciliae assay. This indicates that polyomavirus BK was able to induce antibodies with binding characteristics similar to SLE anti‐DNA antibodies. To further characterize these induced anti‐DNA responses, 10 monoclonal anti‐DNA antibodies (four from Group 1, and six from Group 2) were generated and selected for reactivity with Sl‐nuclease digested CT dsDNA. Their specificity for BK and CT dsDNA molecules, as well as their light and heavy chain variable region cDNA nucleotide sequences were analysed to compare them with known SLE derived anti‐DNA antibodies. All of the 10 antibodies bound strongly to BK dsDNA, while seven also bound to CT dsDNA in competitive ELISA experiments. V‐region analysis revealed that the induced antibodies resembled anti‐DNA antibodies characteristic for murine SLE, and all but one contained arginine in the VH CDR3 region. The arginines present in the monoclonal antibodies originated either from an RF shift from RF1RF3 of the D‐genes or from N‐sequence additions. Taken together, the data demonstrate that anti‐DNA antibodies in response to hyperimmun‐ization with polyomavirus BK have the same characteristics as of those occuring spontaneously in SLE. As virus infection/replication in vivo implies expression of immunogenic (non‐self) DNA‐binding proteins that may render DNA immunogenic, the present results may therefore suggest one physiological mechanism for production of SLE‐related anti‐DNA antibodies.

Anti-DNA antibodies induced by BK virus inoculations. Demonstration of the specificities for eukaryotic dsDNA and synthetic polynucleotides.

The ability of BK virus to induce anti‐DNA antibodies in rabbits, and the ability of these antibodies to bind natural eukaryotic DNA and synthetic polynucleotides have been analysed. The specificity of the binding was assayed by inhibition of anti‐dsDNA and ‐ssDNA ELISA tests with dsDNA, ssDNA, and synthetic single‐stranded as well as double‐stranded polynucleotides The anti‐dsDNA activity of two rabbit antisera was effectively inhibited by dsDNA and ssDNA and poly(dAdT)‐poly(dAdT). The other nucleotide antigens produced relatively loss inhibition. The anti‐ssDNA binding was most efficiently inhibited by the homologous antigen, whereas inhibition by dsDNA only reached approximately 70%, of the maximum as defined by ssDNA as inhibitor. This indicates the existence of a selective anti‐ssDNA antibody population and, a population recognizing both ssDNA and dsDNA within the sera. Cross‐reaction of the induced anti‐DNA antibodies with phospholipid antigens, such as cardiolipin, phosphatidylic acid, and bacterial cell surface, could not be demonstrated We conclude that antibodies resulting from inoculation with BK virus specifically bind to dsDNA and ssDNA and possess a high affinity for the synthetic duplex poly (dAdT). In this way. they have some similarities with anti‐DNA antibodies encountered in SLE (systemic lupus erythematosus) in both man and mouse,

Antibodies to Viral and Mammalian Native DNA in Response to BK Virus Inoculation and Subsequent Immunization with Calf Thymus DNA

Recent studies have demonstrated that anti‐DNA antibodies share important genetical features with antibodies to exogenous antigens, suggesting that anti‐DNA antibody responses may be (auto‐) antigen driven. We have earlier defined three out of five rabbits as anti‐dsDNA antibody responders based on reactivity with calf thymus (CT) dsDNA after inoculation with the human dsDNA virus BK. In the present study we demonstrate that all five animals that received BK virus inoculations produced antibodies to BK virus dsDNA. These antibodies did not cross‐react with CT dsDNA, as shown by inhibition experiments. The anti‐BK dsDNA antibodies persisted over time, in contrast to the anti‐CT dsDNA antibodies that decreased shortly after a peak following the first boost of BK virus. While the anti‐CT dsDNA antibodies decreased, the anti‐BK dsDNA antibodies remained elevated, thus supporting the results of the inhibition experiments which showed that two independent antibody populations are produced after BK virus inoculations. In the three animals producing anti‐mammalian dsDNA antibodies, antibodies recognizing CT dsDNA reappeared after intravenous administration of a complex of CT dsDN A and methylated bovine serum albumin (MBSA) without adjuvant. The latter anti‐CT dsDNA antibodies did not cross‐react with BK dsDNA. In contrast to earlier studies we conclude that mammalian dsDNA may be immunogenic, and that discrete molecular differences in DNA antigens from different sources may induce anti‐dsDNA antibodies specific for dsDNA molecules of different origin.

Bk Virus Terminates Tolerance to Dsdna and Histone Antigens in Vivo

In order to characterize the immune response to BK virus, a human polyomavirus containing dsDNA and host cell histones, we followed the appearance of antibodies in five outbred rabbits after intravenous inoculation with purified infectious BK virus without any adjuvant. The animals were followed for 15 weeks after the first inoculation and booster doses were given after four and eight weeks. Antibodies were studied by ELISA techniques with the BK virus particle, dsDNA, ssDNA or the individual histones as test antigens. Antibodies to BK virus structural proteins were detected in all rabbits. Two out of five rabbits produced antibodies to dsDNA, ssDNA, nucleosomes and histones H1 and H3. Even a weak reactivity to H2B was detected in one serum. The autoantibody response was transient as it declined after a few weeks, but it reappeared after a second boost in one of the rabbits. The other animals did not respond in the same manner. The specificity of the antibodies against dsDNA was ascertained by inhibition studies employing S1 nuclease treated DNA as inhibitor. Furthermore, the dsDNA used as coating antigen was not recognized by a human reference serum with known specificity for ssDNA. The rabbit antisera did not show any reactivity to a panel of other (in this context irrelevant) autoantigens. This suggests that the anti-DNA and -histone antibodies are not a result of non-specific polyclonal B cell activation. Thus, inoculation of dsDNA viruses may represent a new model that allows us to investigate mechanisms responsible for circumvention of tolerance to self molecules.

Seriously injured patients transferred from local hospitals to a university hospital

BACKGROUND We studied diagnostics and stabilizing surgery in severely injured patients transferred from local hospitals to a university hospital. The purpose was to identify a potential for improvement of regional trauma care. MATERIAL AND METHODS The material comprises all severely injured patients (Injury Severity [ISS] Score > 15) transferred from local hospitals to the University Hospital of Northern Norway in the period 01.01.2006 - 31.12.2007. Information about diagnostics, extent of injury and treatment during the first 24 hours after transferral was recorded by retrospective chart review. Emergency surgical interventions are defined according to plans for a national trauma system. RESULTS 6/74 patients underwent emergency surgery at the local hospital (chest tube insertion, external fracture fixation); eight after arrival at the university hospital (chest tube insertion, hemostatic packing of the abdomen and pelvis, external fracture fixation). 66/74 were CT-scanned locally; 37 with a CT multitrauma series (CT caput, neck, thorax, abdomen and pelvis). Of the 62 who had head CT scans performed at a local hospital, the cervical spine was not imaged for 10. For eight of 55 patients who had CT scans of the thorax/abdomen/pelvis intravenous contrast agent was not administered. INTERPRETATION Trauma care at local hospitals may be improved by more systematic imaging, a lower threshold for emergency surgery, and early communication with the university hospital.

Evaluation of a trauma team activation protocol revision: a prospective cohort study

BackgroundCorrect triage based on prehospital information contributes to a better outcome for potentially seriously injured patients. In 2011 we changed the trauma team activation (TTA) criteria in our center in order to improve the high over- and undertriage properties of the protocol. Five criteria that were unable to predict severe injury were removed. In the present study, we evaluated the protocol revision by comparing over- and undertriage in the former and present set of criteria.MethodsAll severely injured patients (Injury Severity Score (ISS) > 15) and all patients admitted with TTA in the period of 01.01.2013 – 31.12.2014 were included in the study. We defined overtriage as the fraction of patients with TTA when ISS ≤15 and undertriage as the fraction of patients without TTA when ISS > 15. We also evaluated triage with the occurrence of emergency procedures immediately after admission.Results324 patients were included, 164 patients had ISS>15, 287 were admitted with TTA. Over- and undertriage were 74 % and 28 % respectively. When we used emergency procedure as reference, the figures were 83 % and 15 % respectively. Undertriaged patients had significantly more neurosurgical injuries and were significantly more often transferred from an acute care hospital.DiscussionOver- and undertriage are almost the same as before the criteria were revised, and higher thanrecommended levels.ConclusionsRevision of the TTA criteria has not improved triage, and further measures are necessary to achieveacceptable levels.