| 1. |
- Alsholm, Linda, et al.
(författare)
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Interrupted transport by the emergency medical service in stroke/transitory ischemic attack : A consequence of changed treatment routines in prehospital emergency care.
- 2019
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The discovery that not all patients who call for the emergency medical service (EMS) require transport to hospital has changed the structure of prehospital emergency care. Today, the EMS clinician at the scene already distinguishes patients with a time-critical condition such as stroke/transitory ischemic attack (TIA) from patients without. This highlights the importance of the early identification of stroke/TIA.AIM: To describe patients with a final diagnosis of stroke/TIA whose transport to hospital was interrupted either due to a lack of suspicion of the disease by the EMS crew or due to refusal by the patient or a relative/friend.METHODS: Data were obtained from a register in Gothenburg, covering patients hospitalised due to a final diagnosis of stroke/TIA. The inclusion criterion was that patients were assessed by the EMS but were not directly transported to hospital by the EMS.RESULTS: Among all the patients who were assessed by the EMS nurse and subsequently diagnosed with stroke or TIA in 2015, the transport of 34 of 1,310 patients (2.6%) was interrupted. Twenty-five of these patients, of whom 20 had a stroke and five had a TIA, are described in terms of initial symptoms and outcome. The majority had residual symptoms at discharge from hospital. Initial symptoms were vertigo/disturbed balance in 11 of 25 cases. Another three had symptoms perceived as a change in personality and three had a headache.CONCLUSION: From this pilot study, we hypothesise that a fraction of patients with stroke/TIA who call for the EMS have their direct transport to hospital interrupted due to a lack of suspicion of the disease by the EMS nurse at the scene. These patients appear to have more vague symptoms including vertigo and disturbed balance. Instruments to identify these patients at the scene are warranted.
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| 2. |
- Andersson, Håkan S., et al.
(författare)
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The alpha-defensin salt-bridge induces backbone stability to facilitate folding and confer proteolytic resistance
- 2012
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 43:4, s. 1471-1483
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Tidskriftsartikel (refereegranskat)abstract
- Salt-bridge interactions between acidic and basic amino acids contribute to the structural stability of proteins and to protein-protein interactions. A conserved salt-bridge is a canonical feature of the alpha-defensin antimicrobial peptide family, but the role of this common structural element has not been fully elucidated. We have investigated mouse Paneth cell alpha-defensin cryptdin-4 (Crp4) and peptide variants with mutations at Arg(7) or Glu(15) residue positions to disrupt the salt-bridge and assess the consequences on Crp4 structure, function, and stability. NMR analyses showed that both (R7G)-Crp4 and (E15G)-Crp4 adopt native-like structures, evidence of fold plasticity that allows peptides to reshuffle side chains and stabilize the structure in the absence of the salt-bridge. In contrast, introduction of a large hydrophobic side chain at position 15, as in (E15L)-Crp4 cannot be accommodated in the context of the Crp4 primary structure. Regardless of which side of the salt-bridge was mutated, salt-bridge variants retained bactericidal peptide activity with differential microbicidal effects against certain bacterial cell targets, confirming that the salt-bridge does not determine bactericidal activity per se. The increased structural flexibility induced by salt-bridge disruption enhanced peptide sensitivity to proteolysis. Although sensitivity to proteolysis by MMP7 was unaffected by most Arg(7) and Glu(15) substitutions, every salt-bridge variant was degraded extensively by trypsin. Moreover, the salt-bridge facilitates adoption of the characteristic alpha-defensin fold as shown by the impaired in vitro refolding of (E15D)-proCrp4, the most conservative salt-bridge disrupting replacement. In Crp4, therefore, the canonical alpha-defensin salt-bridge facilitates adoption of the characteristic alpha-defensin fold, which decreases structural flexibility and confers resistance to degradation by proteinases.
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| 3. |
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| 4. |
- Byberg, Linda, et al.
(författare)
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Nurses’ experiences of caring for patients with tuberculosis – An interview study in Indonesia
- 2019
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Ingår i: International Archives of Nursing and Health Care. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Tuberculosis, TB is an infectious disease affecting millions of people each year and Indonesia have the second highest prevalence in the world. The cure of TB is already existing but hence to factors such as long treatment with severe side-effects results in low compli- ance. The aim of the study was to describe nurse’s con- ceptions of caring for patients suffering from tuberculosis in Yogyakarta, Indonesia. Method: Individual interviews were conducted with ten nurses at different hospitals and primary health centers. The material was analysed with a phenomenographic ap- proach. Findings: Three categories were described; “The concep- tions of tuberculosis as a contagious disease”, “The con- ceptions of the nurse’s role” and “The conceptions of the patient’s situation”. Results showed that precautions and protection of transmission was the most prominent concep- tion related to tuberculosis-care. Another point of view was nurse’s role as an educator to improve patient’s knowledge regarding precautions and treatment plan. Conclusion: To perform nursing, precautions and protec- tion is significant even though medication for TB is free of charge. However, other economic factors remain as well as manage the complexity of TB for example multidrug-resis- tance (MDR), calls for further research.
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| 5. |
- Cirenajwis, Helena, et al.
(författare)
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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
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| 6. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 7. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 8. |
- Forsmark, Annabelle, et al.
(författare)
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Inequalities in pharmacologic treatment of spasticity in Sweden : health economic consequences of closing the treatment gap
- 2020
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Ingår i: Health Economics Review. - : BioMed Central (BMC). - 2191-1991. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Swedish Healthcare Act states that patients should have equal access to healthcare. This study addresses at how this translates to pharmacological treatment of adult spasticity, including injections with botulinum toxin A (BoNT-A) and pumps for intrathecal baclofen (ITB). To address potential economic incentives for treatment differences, the results are also set into a health economic perspective.Thus, the current study provides a detailed and comprehensive overview for informed decision- and policymaking.MethodsBotulinum toxin use was retrieved from sales data. Clinical practice regarding mean BoNT-A treatment dose and proportion used for spasticity indication were validated in five county councils, while the number of ITB pumps were mapped for all county councils. Published costs and quality of life data was used for estimating required responder rates for cost-balance or cost-effectiveness.ResultsThe proportion of patients treated with BoNT-A varied between 5.8% and 13.6% across healthcare regions, with a mean of 9.2% on a national level. The reported number of ITB pumps per 100,000 inhabitants varied between 3.6 and 14.1 across healthcare regions, with a national mean of 6/100,000.The estimated incremental cost for reaching treatment equity was EUR 1,976,773 per year for BoNT-A and EUR 3,326,692 for ITB pumps. Based on expected cost-savings, responder rates ranging between 4% and 15% cancelled out the incremental cost for BoNT-A. Assuming no cost-savings, responder rates of 14% or 36% was required for cost-effectiveness.ConclusionsThere is a marked variation in pharmacologic treatment of adult spasticity in Sweden. Overall, the results indicate an underuse of treatment and need for harmonisation of clinical practice. Furthermore, the incremental cost for reaching treatment equity is likely to be offset by spasticity-associated cost-savings.
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| 9. |
- Gennemark, Peter, et al.
(författare)
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An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
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| 10. |
- Göransson, Ulf, et al.
(författare)
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The Conserved Glu in the Cyclotide Cycloviolacin O2 Has a Key Structural Role
- 2009
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 10:14, s. 2354-2360
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are a large family of plant peptides that are characterised by a head-to-tail circular backbone and three disulfide bonds that are arranged in a cystine knot. This unique structural feature, which is referred to as a cyclic cystine knot, gives the cyclotides remarkable stability against chemical and biological degradation. In addition to their natural function as insecticides for plant defence, the cyclotides have a range of bioactivities with pharmaceutical relevance, including cytotoxicity against cancer cell lines. A glutamic acid residue, aside from the invariable disulfide array, is the most conserved feature throughout the cyclotide family, and it has recently been shown to be crucial for biological activity. Here we have used solution-state NMR spectroscopy to determine the three-dimensional structures of the potent cytotoxic cyclotide cycloviolacin O2, and an inactive analogue in which this conserved glutamic acid has been methylated. The structures of the peptides show that the glutamic acid has a key structural role in coordinating a set of hydrogen bonds in native cycloviolacin O2; this interaction is disrupted in the methylated analogue. The proposed mechanism of action of cyclotides is membrane disruption and these results suggest that the glutamic acid is linked to cyclotide function by stabilising the structure to allow efficient aggregation in membranes, rather than in a direct interaction with a target receptor.
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