| 1. |
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| 2. |
- Baker, Tim, et al.
(författare)
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Single Deranged Physiologic Parameters Are Associated With Mortality in a Low-Income Country
- 2015
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 43:10, s. 2171-2179
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether deranged physiologic parameters at admission to an ICU in Tanzania are associated with in-hospital mortality and compare single deranged physiologic parameters to a more complex scoring system. Design: Prospective, observational cohort study of patient notes and admission records. Data were collected on vital signs at admission to the ICU, patient characteristics, and outcomes. Cutoffs for deranged physiologic parameters were defined a priori and their association with in-hospital mortality was analyzed using multivariable logistic regression. Setting: ICU at Muhimbili National Hospital, Dar es Salaam, Tanzania. Patients: All adults admitted to the ICU in a 15-month period. Measurements and Main Results: Two hundred sixty-nine patients were included: 54% female, median age 35 years. In-hospital mortality was 50%. At admission, 69% of patients had one or more deranged physiologic parameter. Sixty-four percent of the patients with a deranged physiologic parameter died in hospital compared with 18% without (p < 0.001). The presence of a deranged physiologic parameter was associated with mortality (adjusted odds ratio, 4.64; 95% CI, 1.95-11.09). Mortality increased with increasing number of deranged physiologic parameters (odds ratio per deranged physiologic parameter, 2.24 [1.53-3.26]). Every individual deranged physiologic parameter was associated with mortality with unadjusted odds ratios between 1.92 and 16.16. A National Early Warning Score of greater than or equal to 7 had an association with mortality (odds ratio, 2.51 [1.23-5.14]). Conclusion: Single deranged physiologic parameters at admission are associated with mortality in a critically ill population in a low-income country. As a measure of illness severity, single deranged physiologic parameters are as useful as a compound scoring system in this setting and could be termed danger signs. Danger signs may be suitable for the basis of routines to identify and treat critically ill patients.
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| 3. |
- Baker, Tim, et al.
(författare)
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Vital Signs Directed Therapy : Improving Care in an Intensive Care Unit in a Low-Income Country
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Background Global Critical Care is attracting increasing attention. At several million deaths per year, the worldwide burden of critical illness is greater than generally appreciated. Low income countries (LICs) have a disproportionally greater share of critical illness, and yet critical care facilities are scarce in such settings. Routines utilizing abnormal vital signs to identify critical illness and trigger medical interventions have become common in high-income countries but have not been investigated in LICs. The aim of the study was to assess whether the introduction of a vital signs directed therapy protocol improved acute care and reduced mortality in an Intensive Care Unit (ICU) in Tanzania. Methods and Findings Prospective, before-and-after interventional study in the ICU of a university hospital in Tanzania. A context-appropriate protocol that defined danger levels of severely abnormal vital signs and stipulated acute treatment responses was implemented in a four week period using sensitisation, training, job aids, supervision and feedback. Acute treatment of danger signs at admission and during care in the ICU and in-hospital mortality were compared pre and post-implementation using regression models. Danger signs from 447 patients were included: 269 pre-implementation and 178 post-implementation. Acute treatment of danger signs was higher post-implementation (at admission: 72.9% vs 23.1%, p<0.001; in ICU: 16.6% vs 2.9%, p<0.001). A danger sign was five times more likely to be treated post-implementation (Prevalence Ratio (PR) 4.9 (2.9-8.3)). Intravenous fluids were given in response to 35.0% of hypotensive episodes post-implementation, as compared to 4.1% pre-implementation (PR 6.4 (2.5-16.2)). In patients admitted with hypotension, mortality was lower post-implementation (69.2% vs 92.3% p = 0.02) giving a numbers-needed-to-treat of 4.3. Overall in-hospital mortality rates were unchanged (49.4% vs 49.8%, p = 0.94). Conclusion The introduction of a vital signs directed therapy protocol improved the acute treatment of abnormal vital signs in an ICU in a low-income country. Mortality rates were reduced for patients with hypotension at admission but not for all patients.
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| 4. |
- Blixt, Jonas
(författare)
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Studies of experimental brain trauma and ischemia : effects of Epo
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury has attained a lot of scientific and clinical focus during a considerable amount of time but is still as of today regarded a highly lethal condition with a high degree of morbidity amongst the surviving. The complexity of the pathophysiological processes that start immediately after the primary injury are challenging – disruption of the blood-brain barrier (BBB), imbalance in metabolic supply and demand, neuroinflammation and formation of brain edema are some of the components in a plethora of existing processes. The overall aim of this thesis was to characterize pathophysiological processes in brain injury (TBI and ischemia) and investigate effects of erythropoietin (EPO) on these processes, with focus on brain edema, blood-brain barrier, and astrocyte function. In an animal model of TBI we found that the resulting brain edema was caused by an early BBB disruption associated with a decrease in anchoring tight junction proteins as well as a cytotoxic edema and a decreased expression of the water channel aquaporin 4 (AQP4). The BBB disruption lasted for at least 4 days while levels of AQP4 was restored between day 1 and 4. We suggest that the vasogenic component of the edema, partly due to disruption of tight junctions in the BBB, likely is of importance in the early phase, and that the observed decrease in AQP4 expression may inhibit the later resolution of the edema. When analyzing the effect of EPO, we found that post-traumatic administration of daily doses of EPO preserved both structural and functional properties of the BBB by preventing loss of the tight junction component ZO-1, resulting in reduced IgG permeability and possibly water as well. Further, EPO treatment following TBI inhibited the decrease of AQP and cytotoxic brain edema. Most of these functions are related to astrocytes. We further explored effects of erythropoietin on astrocyte function and metabolism in an cell model of ischemia. We found that EPO had positive effects on astrocyte glutamate uptake and metabolism (lactate extrusion and NADH production) and that these effects, at least partly, were mediated by preservation of Na,K-ATPase activity, and function of the Na+/H+ exchanger. EPO may by these mechanisms protect against cytotoxicity and excitotoxicity and contribute to neuroprotection. Taken together our findings, by use of several techniques in cellular and animal-models, indicate that treatment with EPO decrease brain edema, restores BBB function, and have positive effects on glutamate clearance and metabolic functions in astrocytes. These effects are most likely mediated by EPOs anti-inflammatory, glycolysis stimulating, and mitochondria stabilizing functions, and can thereby have a potential neuroprotective role in TBI with secondary ischemic injury, and probably as well in primary brain ischemia. Taken together, as an extremely complex and highly vulnerable organ the brain will keep challenging scientists. We believe that these studies, including aspects regarding both TBI and ischemia, contributes to new insights regarding EPO or EPO-derivates potential beneficial effects in brain injury mechanisms.
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| 5. |
- Eriksson, Per, et al.
(författare)
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Characterization of avian influenza virus attachment patterns to human and pig tissues
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Wild birds of Anseriformes and Charadriiformes are natural reservoirs of influenza A viruses (IAVs). Occasionally, IAVs transmit and adapt to mammalian hosts, and are maintained as epidemic strains in their new hosts. Viral adaptions to mammalian hosts include altered receptor preference of host epithelial sialylated oligosaccharides from terminal alpha 2,3-linked sialic acid (SA) towards alpha 2,6-linked SA. However, alpha 2,3-linked SA has been found in human respiratory tract epithelium, and human infections by avian IAVs (AIVs) have been reported. To further explore the attachment properties of AIVs, four AIVs of different subtypes were investigated on human and pig tissues using virus histochemistry. Additionally, glycan array analysis was performed for further characterization of IAVs' receptor structure tropism. Generally, AIV attachment was more abundant to human tissues than to pig tissues. The attachment pattern was very strong to human conjunctiva and upper respiratory tract, but variable to the lower respiratory tract. AIVs mainly attached to alpha 2,3-linked SA, but also to combinations of alpha 2,3-and alpha 2,6-linked SA. The low attachment of these AIV isolates to pig tissues, but high attachment to human tissues, addresses the question whether AIVs in general require passage through pigs to obtain adaptions towards mammalian receptor structures.
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| 6. |
- Hultberg, Jonas, et al.
(författare)
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In-depth immune profiling reveals advanced B- and T-cell differentiation to be associated with Th1-driven immune dysregulation in common variable immunodeficiency
- 2023
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Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 257
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Tidskriftsartikel (refereegranskat)abstract
- Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by low levels of an-tibodies. In addition to infections, many patients also suffer from T-helper 1-driven immune dysregulation, which is associated with increased mortality. The aim of this study was to perform in-depth characterization of the T and the B cell compartments in a well-defined cohort of patients affected by CVID and correlate the findings to the level of clinical immune dysregulation. We used mass cytometry, targeted proteomics, flow cytometry and functional assays to delineate the immunological phenotype of 15 CVID-affected patients with different levels of immune dysregulation. Unbiased clustering of T cell mass cytometry data correlated with CVID-related immune dysregulation and plasma protein profiles. Expanded CXCR3+ T-bet-expressing B cells correlated with effector memory CD4+ T cell clusters, and increased plasma levels of CXCR3-ligands. Our findings indicate an interplay between B cells and T cells in CVID-related immune dysregulation and provide a better understanding of the underlying pathological mechanisms.
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| 7. |
- Hvarfner, Anna, et al.
(författare)
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Vital Signs Directed Therapy for the Critically Ill : Improved Adherence to the Treatment Protocol Two Years after Implementation in an Intensive Care Unit in Tanzania
- 2020
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Ingår i: Emergency Medicine International. - : HINDAWI LTD. - 2090-2840 .- 2090-2859. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- Treating deranged vital signs is a mainstay of critical care throughout the world. In an ICU in a university hospital in Tanzania, the implementation of the Vital Signs Directed Therapy Protocol in 2014 led to an increase in acute treatments for deranged vital signs. The mortality rate for hypotensive patients decreased from 92% to 69%. In this study, the aim was to investigate the sustainability of the implementation two years later. An observational, patient-record-based study was conducted in the ICU in August 2016. Data on deranged vital signs and acute treatments were extracted from the patients' charts. Adherence to the protocol, defined as an acute treatment in the same or subsequent hour following a deranged vital sign, was calculated and compared with before and immediately after implementation. Two-hundred and eighty-nine deranged vital signs were included. Adherence was 29.8% two years after implementation, compared with 16.6% (p<0.001) immediately after implementation and 2.9% (p<0.001) before implementation. Consequently, the implementation of the Vital Signs Directed Therapy Protocol appears to have led to a sustainable increase in the treatment of deranged vital signs. The protocol may have potential to improve patient safety in other settings where critically ill patients are managed.
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| 8. |
- Kaså, Sophia, et al.
(författare)
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CIRA: cirkulär och inkluderande renovering av allmännyttan : Synergier och förflyttning i systemförändringen mot en hållbarare ROT-process
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trots att cirkulär byggnation och boendes inkludering i bygg- och renoveringsprocesser studerats mycket var för sig, är kombinationen relativt outforskad. Målet med detta projekt var att se vilka synergier som kunde uppstå för ett allmännyttigt bostadsbolag om man arbetade fram en cirkulärare och mer inkluderade ROT-process.Utifrån ett tätt samarbete mellan kommun, fastighetsägare, arkitektkontor och forskningsinstitut utforskades vad en cirkulär och inkluderande ROT-process kunde vara. Genom en innovationsprocess som bland annat innefattade kompetenshöjande insatser, workshops, studiebesök, intervjuer, observationer och olika sorters testning, så utvecklades en gemensam förståelse för den nya processen. En prototyp för en cirkulär och inkluderande ROT-process utformades, som kom att kallas CIRA-processen.Slutsatserna av arbetet blev att det är i de tidiga faserna av ett projekt som cirkulär och inkluderande riktning och strategi måste tas fram. Upphandlingen kommer in tidigare än i en traditionell ROT-process och efter det tar man tillsammans fram nyckeltal och projektmål och utför grundliga inventeringar av den fastigheten projektet gäller. Ytterligare en slutsats är att arbetet behöver göras i partnerskap med alla berörda aktörer, inte minst boende och entreprenörer. I rapporten beskrivs innovationsprocessen och den framtagna CIRA-processen i detalj.
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| 9. |
- Nordén, Rickard, 1977, et al.
(författare)
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Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- A recombinant subunit vaccine (Shingrix((R))) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax((R))). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax((R)), which is produced in fibroblasts, the recombinant gE of Shingrix((R)) is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix((R)). Firstly, recombinant gE produced in CHO cells (Shingrix situation) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (Zostavax situation), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix((R)), and can also be of relevance for development of subunit vaccines to other enveloped viruses.
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| 10. |
- Nyberg, Axel, et al.
(författare)
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Lung-protective ventilation increases cerebral metabolism and non-inflammatory brain injury in porcine experimental sepsis
- 2021
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Ingår i: BMC Neuroscience. - : BioMed Central (BMC). - 1471-2202. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg-1 and nine animals were ventilated with a tidal volume of 10 mL × kg-1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg-1 × h-1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour.RESULTS: No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium-high tidal volume ventilation.CONCLUSIONS: Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.
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