| 1. |
- Sourander, Birger, et al.
(författare)
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No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study
- 2022
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 703-712
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Tidskriftsartikel (refereegranskat)abstract
- Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
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| 2. |
- Yilmaz, Aylin, 1974, et al.
(författare)
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Upper respiratory tract levels of SARS-CoV-2 RNA and duration of viral RNA shedding do not differ between patients with mild and severe/critical COVID-19.
- 2021
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- This study reports longitudinal viral RNA loads from nasopharynx/throat in patients with mild and severe/critical COVID-19. We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract, nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
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| 3. |
- Yilmaz, Aylin, et al.
(författare)
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Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019
- 2021
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
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| 4. |
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| 5. |
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| 6. |
- Andersson, Ulf, 1985-, et al.
(författare)
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Clinical Reasoning among Registered Nurses in Emergency Medical Services : A Case Study
- 2022
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Ingår i: Journal of Cognitive Engineering and Decision Making. - : Sage Publications. - 1555-3434 .- 2169-5032. ; 16:3, s. 123-156
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Tidskriftsartikel (refereegranskat)abstract
- In emergency medical services (EMS), the clinical reasoning (CR) of registered nurses (RNs) working in ambulance care plays an important role in providing care and treatment that is timely, accurate, appropriate and safe. However, limited existing knowledge about how CR is formed and influenced by the EMS mission hinders the development of service provision and decision support tools for RNs that would further enhance patient safety. To explore the nature of CR and influencing factors in this context, an inductive case study examined 34 observed patient-RN encounters in an EMS setting focusing on ambulance care. The results reveal a fragmented CR approach involving several parallel decision-making processes grounded in and led by patients' narratives. The findings indicate that RNs are not always aware of their own CR and associated influences until they actively reflect on the process, and additional research is needed to clarify this complex phenomenon.
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| 7. |
- Andersson, Ulf, 1985-, et al.
(författare)
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Clinical reasoning in the emergency medical services: an integrative review
- 2019
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Clinical reasoning is the process of gathering and understanding information conducted by clinicians in the emergency medical services (EMS) so as to make informed decisions. Research on clinical reasoning spans several disciplines, but a comprehensive view of the process is lacking. To our knowledge, no review of clinical reasoning in the EMS has been conducted.Aim: The aim was to investigate the nature, deployment, and factors influencing EMS clinicians’ clinical reasoning by means of a review.Method: Data was collected through searches in electronic databases, networking among research teams ,colleagues and friends, “grey literature,” and through ancestry searches. A total of 38 articles were deemed eligible for inclusion and were analyzed using descriptive thematic analysis. The analysis resulted in an overarching finding -namely, the importance for EMS clinicians to adjust for perceived control in unpredictable situations. Within this finding, 3 themes emerged in terms of EMS clinicians’ clinical reasoning: (1) maintaining a holistic view of the patient; (2) keeping an open mind; and (3) improving through criticism. Seven subthemes subsequently emerged from these three themes.Results: This review showed that EMS clinicians’ clinical reasoning begins with the information that they are given about a patient. Based on this information, clinicians calculate the best route to the patient and which equipment to use, and they also assess potential risks. They need to be constantly aware of what is happening on the scene and with the patient and strive to control the situation. This striving also enables EMS clinicians to work safely and effectively in relation to the patient, their relatives, other clinicians, associated organizations, and the wider community. A lack of contextually appropriate guidelines results in the need for creativity and forces EMS clinicians to use “workarounds” to solve issues beyond the scope of the guidelines available. In addition, they often lack organizational support and fear repercussions such as litigation, unemployment, or blame by their EMS or healthcare organization or by patients and relatives.Conclusion: Clinical reasoning is influenced by several factors. Further research is needed to determine which influencing factors can be addressed through interventions to minimize their impact on patient outcomes.
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| 8. |
- Andersson, Ulf, 1985-, et al.
(författare)
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Organizational factors influencing clinical reasoning in a Swedish emergency medical service organization: An explorative qualitative case study
- 2023
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Ingår i: Paramedicine. - : Sage Publications. - 2753-6386 .- 2753-6386.
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionClinical reasoning (CR) among healthcare professionals working in emergency medical services (EMS) who focus on ambulance care is a vital part of ensuring timely and safe patient care. The EMS environment continually fluctuates, so clinicians constantly need to adapt to new situations. Organizational support is described as important for CR, but overall, research on organizational influences for CR in an EMS context is lacking. An increased understanding of these influencing factors can assist in the development of EMS by strengthening CR among clinicians. Therefore, the purpose of this study was to investigate the organizational factors influencing EMS clinicians’ CR.MethodsUsing a qualitative single case study design, an EMS organization in southwestern Sweden was explored. Data were collected from participant observations of patient encounters, individual and group interviews with clinicians and organizational representatives, and organizational document audits. Data were analyzed using qualitative content analysis and triangulation of data sources.ResultsThe results revealed several organizational influencing factors. Collaboration and information sharing internally and externally were emphasized as essential components influencing CR. Additionally, the structure for the clinicians’ ‘room for action’ appeared confused and created uncertainties for CR related to decision mandates.ConclusionThe conclusion is that organizational factors do play an important role in clinicians’ CR. Moreover, the EMS community needs to develop suitable forums for discussing and developing these influencing factors across organizational hierarchies. Finally, clarification is needed on clinicians’ ‘room for action’ within their own organization but also with possible collaborators.
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| 9. |
- Andersson, Ulf, 1985-, et al.
(författare)
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Situation awareness in Sweden’s emergency medical services : a goal-directed task analysis
- 2023
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Ingår i: Discover Health Systems. - 2731-7501. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Situation awareness is knowing what is going on in the situation. Clinicians working in the emergency medical services (EMS) encounter numerous situations in various conditions, and to be able to provide efficient and patient safe care they need to understand what is going on and possible projections of the current situation. The design of this study encompassed a Goal-Directed Task analysis where situation awareness information requirements were mapped in relation to goals related to various aspects of the EMS mission. A group of 30 EMS subject matter experts were recruited and answered a web-based survey in three rounds related to what they though themselves or a colleague might need to achieve situation awareness related to the specific goals of various situations. The answers were analysed using content analysis and descriptive statistics. Answers reached consensus at a predetermined level of 75%. Those who reached consensus were entered into the final goal-directed task analysis protocol. The findings presented that EMS clinicians must rely on their own, or their colleagues prior experience or knowledge to achieve situation awareness. This suggests that individual expertise plays a crucial role in developing situation awareness. There also seems to be limited support for situation awareness from organizational guidelines. Furthermore, achieving situation awareness also involves collaborative efforts from the individuals involved in the situation. These findings could add to the foundation for further investigation in this area which could contribute to the development of strategies and tools to enhance situation awareness among EMS clinicians, ultimately improving patient care and safety.
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| 10. |
- Beck-Friis, Thomas, et al.
(författare)
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Burden of rotavirus infection in hospitalized elderly individuals prior to the introduction of rotavirus vaccination in Sweden
- 2019
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 119, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rotavirus gastroenteritis (GE) in the elderly has been much less studied than in children. Objectives: The aim of this study was to determine the morbidity and mortality for elderly hospitalized patients with rotavirus GE prior to the introduction of rotavirus vaccination in Sweden, and to investigate the epidemiology of rotavirus genotypes in these patients. Study design: All patients 60 years or older who were hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, and were rotavirus positive in a clinical diagnostic test from 2009 to 2016, were included. Medical records were reviewed and rotavirus genotyping real-time PCR was performed. Results: One hundred and fifty-nine patients were included, corresponding to an annual incidence of hospitalization due to rotavirus GE of 16/100 000 inhabitants aged 60 years or older. G2P[4] was the most common genotype, followed by G1P[8] and G4P[8]. The majority of patients had community-onset of symptoms and no or few pre-existing health disorders. Four patients (2.5%) died within 30 days of sampling. Patients with hospital-onset rotavirus GE had a longer median length of stay following diagnosis compared with patients with community-onset of symptoms (19 vs. 5 days, p = 0.001) and higher 30-day mortality (8.6% (3/35) vs. < 1% (1/124), p = 0.03). Conclusions: Hospitalization due to rotavirus GE among the elderly seems to mainly affect otherwise healthy individuals and is associated with low 30-day mortality.
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| 11. |
- Bergknut, Magnus, et al.
(författare)
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Identification of potentially toxic compounds in complex extracts of environmental samples using gas chromatography-mass spectrometry and multivariate data analysis
- 2007
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Ingår i: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-217
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography-time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 12. |
- Bergknut, Magnus, et al.
(författare)
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Identification of potentially toxic compounds in complex extracts of environmental samples using GC-MS and multivariate data analysis
- 2007
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Ingår i: Environmental Toxicology and Chemistry. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-17
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography–time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 13. |
- Edén, Arvid, 1975, et al.
(författare)
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CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series.
- 2021
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Ingår i: Neurology. - 1526-632X. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements.We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe COVID-19 and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4/6), suspected meningitis (1/6) and dysgeusia (1/6). SARS-CoV-2 infection was confirmed by rtPCR analysis of nasopharyngeal swabs.SARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in one but not in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. Median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.Our results on patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections, and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
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| 14. |
- Edén, Arvid, 1975, et al.
(författare)
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Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.
- 2010
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Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40
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Tidskriftsartikel (refereegranskat)abstract
- Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
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| 15. |
- Forsberg, Viviane, 1981-, et al.
(författare)
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Photodetector of multilayer exfoliated MoS2 deposited on polyimide films
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We fabricated a photodetector based on multilayer molybdenum disulfide (MoS2) by micromechanical cleavage of a molybdenite crystal using a polyimide film. We deposited 40 nm of gold by vacuum sputtering and copper tape was used for the contacts. Without any surface treatment, we achieved high responsivity at different incident optical power. The calculated responsivity was 23 mA/W of incident optical power in the range between 400 and 800 nm. For the responsivity measurement it was estimated that MoS2 have a bandgap of 1.6 eV, which lies between monolayer and multilayer films. The thickness of the MoS2 thin film was determined by Raman spectroscopy evaluating the difference between the in plane and out of plane Raman modes. The measurement of IV curves indicated Ohmic contacts in respect to the Au regardless of the incident optical power. Our device fabrication was much simpler than previous reported devices and can be used to test the light absorption and luminescence capabilities of exfoliated MoS2.
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| 16. |
- Gustavsson, Lars, et al.
(författare)
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Venous lactate levels can be used to identify patients with poor outcome following community-onset norovirus enteritis
- 2012
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44:10, s. 782-787
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Tidskriftsartikel (refereegranskat)abstract
- Background: Norovirus enteritis (NVE) can be fatal in frail patients. High blood lactate levels indicate hypoperfusion and predict mortality in many infectious diseases. The objective was to determine the frequency and association with mortality of elevated lactate levels in patients with community-onset NVE. Methods: A retrospective cohort study was performed. All hospitalized adult patients with community-onset NVE verified by polymerase chain reaction during the period August 2008 to June 2009 were included. Vital signs and venous lactate on arrival, co-morbid conditions, and time of death were registered. The outcome measure was 30-day all-cause mortality. Results: Eighty-two patients with a median age of 77 y (interquartile range (IQR) 53-86 y) were included, of whom 47 (57%) were female and 49 (60%) had at least 1 major co-morbid condition. Lactate levels were above the upper limit of normal (ULN; 1.6 mmol/l) in 45 patients (55%). The overall 30-day mortality rate was 7% (6/82). Mortality was 18% (5/28) with lactate >= 2.4 mmol/l (> 50% above the ULN) on admission compared to 2% (1/54) with lactate < 2.4 mmol/l (p < 0.05). Patients who died had a higher median lactate level compared to survivors: 4.5 (IQR 2.7-7.9) mmol/l vs 1.7 (IQR 1.3-2.5) mmol/l, respectively (p < 0.01). The adjusted odds ratio for death within 30 days for a 1 mmol/l increase in lactate was 2.5 (95% confidence interval 1.003-6.3, p = 0.049). Conclusions: We observed a high proportion of patients with elevated lactate levels in community-onset NVE. Lactate elevation could predict mortality. Measurement of blood lactate may be a valuable tool in the clinical management of patients with a suspected norovirus infection.
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| 17. |
- Kanberg, Nelly, et al.
(författare)
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Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.
- 2020
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 95:12
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
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| 18. |
- Lundgren, Anna, 1974, et al.
(författare)
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Plasmablasts in previously immunologically naive COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses
- 2023
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Ingår i: Clinical and Experimental Immunology. - 0009-9104 .- 1365-2249. ; 213:2, s. 173-89
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Tidskriftsartikel (refereegranskat)abstract
- Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin beta 1, only some integrin beta 7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients. During an infection, plasmablasts circulating in blood represent ongoing formation of antibody-producing cells from activated B cells. Here we study the early plasmablasts in previously naive COVID-19 patients arriving at hospital. We find extensive cross-reactivity to circulating and non-circulating beta-coronaviruses, that IgA1 responses dominate, and that the cells express markers suggesting mucosal homing.
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| 19. |
- Lundin, Samuel B, 1970, et al.
(författare)
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A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein
- 2023
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens. MethodsWe herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays. ResultsWe identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S. ConclusionWe present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.
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| 20. |
- Marklund, Emelie, et al.
(författare)
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Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
- 2020
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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| 21. |
- Persson, Josefine, 1980, et al.
(författare)
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Stratification of COVID-19 patients based on quantitative immune-related gene expression in whole blood.
- 2022
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Ingår i: Molecular immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 145, s. 17-26
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Tidskriftsartikel (refereegranskat)abstract
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes mild symptoms in the majority of infected individuals, yet in some cases it leads to a life-threatening condition. Determination of early predictive biomarkers enabling risk stratification for coronavirus disease 2019 (COVID-19) patients can inform treatment and intervention strategies. Herein, we analyzed whole blood samples obtained from individuals infected with SARS-CoV-2, varying from mild to critical symptoms, approximately one week after symptom onset. In order to identify blood-specific markers of disease severity status, a targeted expression analysis of 143 immune-related genes was carried out by dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA). The clinically well-defined subgroups of COVID-19 patients were compared with healthy controls. The transcriptional profile of the critically ill patients clearly separated from that of healthy individuals. Moreover, the number of differentially expressed genes increased by severity of COVID-19. It was also found that critically ill patients can be distinguished by reduced peripheral blood expression of several genes, which most likely reflects the lower lymphocyte counts. There was a notable predominance of IFN-associated gene expression in all subgroups of COVID-19, which was most profound in critically ill patients. Interestingly, the gene encoding one of the main TNF-receptors, TNFRS1A, had selectively lower expression in mild COVID-19 cases. This report provides added value in understanding COVID-19 disease, and shows potential of determining early immune transcript signatures in the blood of patients with different disease severity. These results can guide further explorations to uncover mechanisms underlying immunity and immunopathology in COVID-19.
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| 22. |
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| 23. |
- Schaefer, Stephan, et al.
(författare)
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Introduction
- 2018
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Ingår i: Working and Organizing in the Digital Age. - 9789198439410 ; , s. 9-18
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 24. |
- Sundell, Nicklas, et al.
(författare)
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Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections
- 2019
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Ingår i: Eurosurveillance. - 1560-7917. ; 24:17, s. 2-12
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Tidskriftsartikel (refereegranskat)abstract
- In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naive (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples geno-typed. Cases were classified as naive, break-through or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naive infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naive infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from break-through infections was identified. Our results indicate that a high risk of onward transmission is limited to naive infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.
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| 25. |
- Zhang, Renyun, et al.
(författare)
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Soap-film coating : High-speed deposition of multilayer nanofilms
- 2013
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Ingår i: Scientific Reports. - Nature Publishing Group : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. Art. no. 1477-
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Tidskriftsartikel (refereegranskat)abstract
- The coating of thin films is applied in numerous fields and many methods are employed for the deposition of these films. Some coating techniques may deposit films at high speed; for example, ordinary printing paper is coated with micrometre-thick layers of clay at a speed of tens of meters per second. However, to coat nanometre thin films at high speed, vacuum techniques are typically required, which increases the complexity of the process. Here, we report a simple wet chemical method for the high-speed coating of films with thicknesses at the nanometre level. This soap-film coating technique is based on forcing a substrate through a soap film that contains nanomaterials. Molecules and nanomaterials can be deposited at a thickness ranging from less than a monolayer to several layers at speeds up to meters per second. We believe that the soap-film coating method is potentially important for industrial-scale nanotechnology.
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