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| 3. |
- Wallentin, Lars, 1943-, et al.
(författare)
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Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II) : 15 year follow-up of a prospective, randomised, multicentre study
- 2016
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Ingår i: The Lancet. - : ELSEVIER SCIENCE INC. - 0140-6736 .- 1474-547X. ; 388:10054, s. 1903-1911
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Tidskriftsartikel (refereegranskat)abstract
- Background The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up. Methods The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat. Findings At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p= 0.0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p(interaction) = 0.0182), patients with elevated troponin T (778 days, 357-1165; p (interaction) = 0.0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; p (interaction) = 0.0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830-1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p< 0.0001). Interpretation During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.
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| 5. |
- Ståhle, Lars, et al.
(författare)
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Effects of Food or Sleep Deprivation During Civilian Survival Training on Clinical Chemistry Variables
- 2013
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Ingår i: Wilderness & environmental medicine (Print). - : Elsevier BV. - 1080-6032 .- 1545-1534. ; 24:2, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- Objective.-To describe clinical chemistry and weight changes after short-term food or sleep deprivation or multiple deprivations during civilian survival training. Methods.-Data from one baseline-controlled two-period crossover study designed to compare sleep deprivation for up to 50 hours with food deprivation for up to 66 hours (n = 12) and data from regular multiple-deprivations survival training comparing participants (n =-33) with nondeprived instructors (n = 10). Results.-Food deprivation was associated with decreased body weight, blood glucose, serum triglycerides, sodium, chloride, and urine pH, and there were increases in blood and urine ketones and. serum free fatty acids. Sleep deprivation was associated with a minor decrease in hemoglobin and erythrocyte particle count and volume fraction and an increase in leukocytes. Conclusions.-The clinical chemistry and body weight changes associated with food deprivation were qualitatively similar to those observed in fasting obese patients but developed quicker in the survival training setting. Sleep deprivation had few effects on the clinical chemistry profile except for hematological variables. Physicians evaluating clinical chemistry data from patients subjected to short-term food or sleep deprivation should take the physiological state into account in their assessment.
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| 6. |
- Ståhle, Lars, et al.
(författare)
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Effects of Sleep or Food Deprivation During Civilian Survival Training on Cognition, Blood Glucose and 3-OH-butyrate
- 2011
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Ingår i: Wilderness & environmental medicine (Print). - 1080-6032 .- 1545-1534. ; 22:3, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives.-The study was designed to compare effects of food deprivation (FD) and sleep deprivation (SD) on cognition during survival training. Methods.-In a cross-over design (n = 12), the effects of FD (up to 66 hours followed by 500 kcal intake over 24 hours) and SD (up to 50 hours) on cognitive variables, blood glucose, and 3-OH-butyrate were studied. Results.-Food deprivation and SD impaired attention-dependent tasks. The FD impairment of simple reaction time was independent of blood glucose levels, which were normalized by a 500 kcal intake over 24 hours while the reaction time was not. Sleep deprivation and FD impaired maze-solving performance on all variables except rule breaks, which were significantly occurring after 50 hours of SD. Delayed word recall was impaired by SD for 50 hours. On the Balloon Analogue Risk Task, SD was associated with reduced risk-taking. In a gambling task, both SD for 50 hours and FD for 66 hours were associated with a tendency to make early choices when presented with consecutive choices, but the risk-taking was not affected. Conclusions.-Sleep deprivation has multiple cognitive effects, including attention, memory, visual-spatial ability, and risk-taking. Food deprivation had no affect on risk-taking, while the other tasks were affected in a way similar to SD but were less pronounced. The FD effects on cognition did not appear to depend on blood sugar levels. The need to sleep should be prioritized in survival situations to avoid cognitive impairment.
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| 7. |
- Yilmaz, Aylin, 1974, et al.
(författare)
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Cerebrospinal fluid and plasma HIV-1 RNA levels and lopinavir concentrations following lopinavir/ritonavir regimen.
- 2004
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 36:11-12, s. 823-8
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to study the effect of lopinavir/ritonavir on cerebrospinal fluid (CSF) viral load as part of an antiretroviral combination treatment for HIV-1 infected individuals, and to determine the steady-state concentrations of lopinavir in CSF in relationship to plasma concentrations. Paired CSF and plasma samples from 12 antiretroviral-naïve HIV-1 infected patients starting combination therapy containing lopinavir/ritonavir were collected at baseline, and during treatment at a first follow-up at median 3.0 months (range 2.6-6.0 months), and at a second follow-up at median 12.1 months (range 6.0-16.5 months). Levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, and lopinavir concentration were analysed. In addition, CSF and plasma lopinavir concentrations in 4 patients already on combination therapy including lopinavir/ritonavir were analysed. Nine of 11 patients had undetectable viral load in CSF and 5/11 in plasma at the first follow-up. At the second follow-up 7/7 had undetectable viral load in CSF and 9/9 in plasma. Intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly both in CSF and serum. The total CSF concentrations of lopinavir were of the same order of magnitude as the unbound concentrations in plasma. Lopinavir mean (+/-SD) concentrations were 42.1 (+/-31.5) nM in CSF and 52.7 (+/-25.2) nM unbound in plasma. We found that antiretroviral combination therapy including lopinavir/ritonavir substantially decreases the viral load, both in CSF and plasma, as well as the intrathecal immunoactivation, measured by beta2-microglobulin and neopterin. CSF concentrations of lopinavir were low, but probably sufficient to have a virological effect.
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| 8. |
- Yilmaz, Aylin, 1974, et al.
(författare)
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Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study.
- 2006
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Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The way various antiretroviral drugs and drug combinations affect HIV-1 infection in the central nervous system is still largely unknown. The aim of this study was to determine the cerebrospinal fluid (CSF) steady-state concentrations of saquinavir and nelfinavir in relation to plasma concentrations, and to study their effect in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) on CSF viral loads, intrathecal immunoactivation, and blood-brain barrier integrity. METHODS: Paired CSF and plasma samples from 8 antiretroviral-naïve HIV-1 infected patients starting combination therapy with saquinavir, nelfinavir, and two nucleoside analogues were collected prior to treatment, and again after approximately 12 and 48 weeks of antiretroviral therapy. Additional plasma samples were taken at weeks 2, 4, 8, 24, and 36. The concentrations of protease inhibitors were analysed, as were levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, albumin ratio, IgG index, and monocytic cell count. RESULTS: None of the patients in the study presented with HIV-1 RNA < 50 copies/mL in CSF or plasma prior to treatment, compared to 5/7 at the end of the study. Signs of cell-mediated intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly in both CSF and serum, although only 1/7 reached normal CSF neopterin levels after 48 weeks of treatment. There was no significant reduction of albumin ratio, IgG index or CSF monocytic cell count. Saquinavir median (range) concentrations were < 2.5 (< 2.5-96.0) nM unbound in plasma, and < 2.5 (< 2.5-9.0) nM total in CSF. Nelfinavir median (range) concentrations were 10.0 (< 2.0-31.0) nM unbound in plasma, and < 2.0 (< 2.0-23.0) nM total in CSF. Saquinavir and nelfinavir were detectable in 7/15 and 9/15 CSF samples, respectively. CONCLUSION: Saquinavir and nelfinavir, in combination with two NRTIs, decrease the CSF viral load and, to a lesser extent, intrathecal immunoactivation. We found reasonably high CSF concentrations of nelfinavir, but suboptimal concentrations of saquinavir.
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| 9. |
- Aarnio, Mikko
(författare)
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Visualization of Peripheral Pain Generating Processes and Inflammation in Musculoskeletal Tissue using [11C]-D-deprenyl PET
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An objective visualization and quantification of pain-generating processes in the periphery would alter pain diagnosis and represent an important paradigm shift in pain research. Positron emission tomography (PET) radioligand [11C]-D-deprenyl has shown an elevated uptake in painful inflammatory arthritis and whiplash-associated disorder. However, D-Deprenyl’s molecular binding target and uptake mechanism in inflammation and musculoskeletal injuries are still unknown. The present thesis aimed to gain insight into the mechanisms of D-deprenyl binding and uptake and to verify whether pain-associated sites and inflammation in acute musculoskeletal injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET-computed tomography (PET/CT).To identify the D-deprenyl binding target, a high-throughput analysis and competitive radioligand binding studies were performed. D-deprenyl inhibited monoamine oxidase A (MAO-A) activity by 55%, MAO-B activity by 99% and angiotensin-converting enzyme (ACE) by 70%, which identified these enzymes as higher-affinity targets. Furthermore, radioligand receptor binding assays pointed favorably towards the concept of MAO-B as the primary target. To investigate the biochemical characteristics of the binding site, we used radioligand binding assays to assess differences in the binding profile in inflamed human synovial membranes exhibiting varying levels of inflammation. D-deprenyl bound to a single, saturable population of membrane-bound protein in synovial membrane homogenates and the level of inflammation correlated with an increase in D-deprenyl binding affinity.To verify whether D-deprenyl can visualize pain-generating processes, patients with musculoskeletal injuries were investigated and followed-up with [11C]-D-deprenyl PET/CT. In the study of eight patients with ankle sprain, the molecular aspects of inflammation and tissue injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. The pain coexisted with increased [11C]-D-deprenyl uptake. In the study of 16 whiplash patients, an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self-rated disability.To further evaluate D-Deprenyl’s usefulness as a marker of inflammation, three PET tracers were compared in an animal PET/CT study. Preliminary findings showed that [11C]-D-deprenyl had an almost identical uptake pattern when compared with [11C]-L-deprenyl. The two deprenyl enantiomers showed no signs of specific binding or trapping and therefore may not be useful to study further in models of inflammatory pain, surgical pain, or both.This thesis demonstrates that D-deprenyl visualizes painful inflammation in musculoskeletal injuries and that the probable underlying mechanism of [11C]-D-deprenyl uptake is binding to MAO.
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| 11. |
- Alström, Ulrica, et al.
(författare)
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Cost analysis of re-exploration for bleeding after coronary artery bypass graft surgery
- 2012
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Ingår i: British Journal of Anaesthesia. - : Oxford University Press (OUP): Policy B. - 0007-0912 .- 1471-6771. ; 108:2, s. 216-222
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Tidskriftsartikel (refereegranskat)abstract
- Background. Re-exploration for bleeding after cardiac surgery is an indicator of substantial haemorrhage and is associated with increased hospital resource utilization. This study aimed to analyse the costs of re-exploration and estimate the costs of haemostatic prophylaxis. less thanbrgreater than less thanbrgreater thanMethods. A total of 4232 patients underwent isolated, first-time, coronary artery bypass graft (CABG) surgery during 2005-8. Each patient re-explored for bleeding (n = 127) was matched with two controls not requiring re-exploration (n = 254). Cost analysis was based on resource utilization from completion of CABG until discharge. A mean cost per patient for re-exploration was calculated. Based on this, the net cost of prophylactic treatment with haemostatic drugs for preventing re-exploration was calculated. less thanbrgreater than less thanbrgreater thanResults. Patients undergoing re-exploration had higher exposure to clopidogrel before operation, prolonged stays in the intensive care unit, and more blood transfusions than controls. The mean incremental cost for re-exploration was (sic)6290 [95% confidence interval (CI) (sic)3408-(sic)9173] per patient, of which 48% [(sic)3001 (95% CI (sic)249-(sic)2147)] was due to prolonged stay, 31% [(sic)1928 (95% CI (sic)1710-(sic)2147)] to the cost of surgery/anaesthesia, 20% [(sic)1261 (95% CI (sic)1145-(sic)1378)] to the increased number of blood transfusions, and andlt;2% [(sic)100 (95% CI (sic)39-(sic)161)] to the cost of haemostatic drugs. A cost model, at an estimated 50% efficacy for recombinant activated clotting factor VIIa and a 50% expected risk for re-exploration without prophylaxis, demonstrated that to be cost neutral, prophylaxis of four patients needed to result in one avoided re-exploration. less thanbrgreater than less thanbrgreater thanConclusions. The resource utilization costs were substantially higher in patients requiring re-exploration for bleeding. From a strict cost-effectiveness perspective, clinical interventions to prevent haemorrhage might be underutilized.
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| 12. |
- Berghauser Pont, Meta, 1972, et al.
(författare)
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PST
- 2019
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Annan publikation (mjukvara/multimedium) (övrigt vetenskapligt/konstnärligt)abstract
- PST is a tool for performing space syntax and regular accessibility analyses. It currently consists of two main parts - a C++ and Python library called Pstalgo and a plugin for the desktop application QGIS.PST is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version. The GNU General Public License is intended to guarantee your freedom to share and change all versions of a program--to make sure it remains free software for all its users.For latest download visit either the Chalmers publication page, or find "Releases" on the Github page.
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| 13. |
- Christersson, Christina, et al.
(författare)
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Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
- 2020
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR).METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis.RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year.CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
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| 14. |
- Christersson, Christina, et al.
(författare)
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Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis : risk factors and antithrombotic treatment
- 2020
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Ingår i: European Heart Journal, Supplement. - : OXFORD UNIV PRESS. - 1520-765X .- 1554-2815. ; 22:C, s. C26-C33
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Tidskriftsartikel (refereegranskat)abstract
- The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events. The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event. All patients performing an bioSAVR or a TAVI 2008-2014 were identified in the SWEDEHEART registry and included in the study (n =10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry. The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy. Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.
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| 16. |
- Ekroth, Rolf, 1944, et al.
(författare)
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Does off-pump coronary surgery endanger long term survival?
- 2008
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 42:2, s. 99-101
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this issue Ibrahim and co-authors report on technical hazards of off-pump (without heart lung machine) coronary surgery 1. Their findings are in line with meta-analyses of randomized trials which indicate that under-grafting and graft-failures are more common after off-pump than after standard operations. The risk that the objectives of coronary bypass surgery are endangered is discussed in relation to evidence based medicine. A moratorium is suggested until conclusive data are available.
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| 17. |
- Elsherbiny, Doaa, 1974-
(författare)
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Pharmacokinetic drug-drug interactions in the management of malaria, HIV and tuberculosis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malaria, Human Immunodeficiency Virus (HIV) and tuberculosis (TB) are global health problems having their worst situation in sub-Saharan Africa. Consequently, concomitant use of antimalarial, antiretroviral and antitubercular drugs may be needed, resulting in a potential risk of drug-drug interactions.Cytochrome P-450 (CYP) enzyme induction/inhibition may lead to drug-drug interactions and can be detected by probe drugs. An analytical method was developed for the quantitation of mephenytoin, CYP2B6 and CYP2C19 probe, and its metabolites. Induction/inhibition of principal CYP enzymes by the antimalarials; artemisinin, dihydroartemisinin, arteether, artemether and artesunate, was evaluated using the 4-hour plasma concentration ratios of probe drugs and their metabolites along with modelling the population pharmacokinetics of S-mephenytoin and its metabolites. The extent of change in enzymatic activities was different among the antimalarials, with artemisinin having strongest capacity for induction and inhibition, consequently, the strongest potential risk for drug-drug interactions. Drug-drug interactions between the antitubercular rifampicin and the antiretrovirals nevirapine and lopinavir were assessed, in TB/HIV patients, by developing population pharmacokinetic models. Rifampicin increased nevirapine oral clearance. Simulations suggested that increasing the nevirapine dose to 300 mg twice daily when co-administered with rifampicin, would result in nevirapine concentrations above subtherapeutic levels, with minimum exposure above the recommended maximum concentration. Lopinavir is co-formulated with ritonavir in the ratio of 4:1. In children, increasing ritonavir dose four times did not completely compensate the enhancement of lopinavir oral clearance caused by rifampicin. However, the predicted lopinavir trough concentration was above the recommended minimum therapeutic concentration.The work presented in this thesis followed an investigation line though not done for a particular drug. First the CYP enzymes involved in the interaction are identified. Afterwards, the expected drug-drug interaction is investigated where the potentially interacting drugs are concomitantly administered and an adjustment in the dose regimen is proposed that is subsequently evaluated.
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| 24. |
- Kågedal, Matts, et al.
(författare)
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A positron emission tomography study in healthy volunteers to estimate mGluR5 receptor occupancy of AZD2066-Estimating occupancy in the absence of a reference region
- 2013
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 82, s. 160-169
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Tidskriftsartikel (refereegranskat)abstract
- AZD2066 is a new chemical entity pharmacologically characterized as a selective, negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5). Antagonism of mGluR5 has been implicated in relation to various diseases such as anxiety, depression, and pain disorders. To support translation from preclinical results and previous experiences with this target in man, a positron emission tomography study was performed to estimate the relationship between AZD2066 plasma concentrations and receptor occupancy in the human brain, using the mGluR5 radioligand [C-11]-ABP688. The study involved PET scans on 4 occasions in 6 healthy volunteers. The radioligand was given as a tracer dose alone and following oral treatment with different doses of AZD2066. The analysis was based on the total volume of distribution derived fro m each PET-assessment. A non-linear mixed effects model was developed where ten delineated brain regions of interest from all PET scans were included in one simultaneous fit. For comparison the analysis was also performed according to a method described previously by Lassen et al. (1995). The results of the analysis showed that the total volume of distribution decreased with increasing drug concentrations in all regions with an estimated Kipl of 1170 nM. Variability between individuals and occasions in non-displaceable volume of distribution could explain most of the variability in the total volume of distribution. The Lassen approach provided a similar estimate for Kipl, but the variability was exaggerated and difficult to interpret.
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| 25. |
- Laasonen, Leena, et al.
(författare)
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Radiographic scoring systems for psoriatic arthritis are insufficient for psoriatic arthritis mutilans : results from the Nordic PAM Study
- 2020
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Ingår i: Acta Radiologica Open. - : SAGE PUBLICATIONS LTD. - 2058-4601. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis (PsA).Purpose: To describe the radiological features in PAM and explore whether existing scoring systems for radiological damage in psoriatic arthritis are applicable for PAM.Material and Methods: Radiographs were scored according to the modified Sharp-van der Heijde (mSvdH) and the Psoriatic Arthritis Ratingen Score (PARS) systems for PsA.Results: At inclusion, 55 PAM patients (49% women, mean age 58 +/- 12 years) had conventional radiographs of both hands and feet. A total of 869 PAM joints were detected and 193 joints with ankylosis. The mean total mSvdH score was 213.7 +/- 137.8 (41% of maximum) with a higher score for hands than for feet: 136.6 +/- 90.1 vs. 79.1 +/- 60.9. However, the total score was relatively higher in the feet than in the hands when compared to the highest possible scoring (47% vs. 38% of max). The mean total PARS score was 126.3 +/- 79.6 (35% of max). Scoring for joint destruction was higher than for proliferation (22% vs. 11% of max). Strong correlation was found between mSvdH and PARS (r(2) = 0.913). A significant correlation was found between scoring and duration of arthritis and the Health Assessment Questionnaire. History of smoking, BMI, and gender did not influence the scoring values.Conclusions: The two scoring systems studied may not be ideal to indicate progression of PAM in advanced disease since they reach ceiling effects rather early. Therefore, reporting early signs suggestive of PAM, e.g. signs of pencil-in-cup deformities or osteolysis, is crucial. This would reveal the presence of PAM and might lead to improved treatment in order to minimize joint damage.
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| 26. |
- Lagerqvist, Bo, 1952-, et al.
(författare)
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5-year outcomes in the FRISC-II randomised trial of an invasive versus a non-invasive strategy in non-ST-elevation acute coronary syndrome : a follow-up study
- 2006
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 368:9540, s. 998-1004
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The FRISC-II invasive trial compared an early invasive with a non-invasive strategy in terms of death and myocardial infarction in non-ST-elevation acute coronary syndrome. We present 5-year follow-up results, overall and in subgroups based on recommended risk stratification criteria. METHODS: In the FRISC-II trial, 2457 patients with non-ST-elevation acute coronary syndrome were randomised to early invasive strategy (coronary angiography and, if appropriate, revascularisation, within 7 days from admission) or non-invasive primarily medical strategy. Risk stratification was done on the basis of risk indicators at randomisation: age older than 65 years, male sex, diabetes mellitus, previous myocardial infarction, ST-segment depression, raised troponin concentration (>0.03 mug/L), and raised C-reactive protein or interleukin 6. Information on events after 24 months was taken from national registries. Analyses were done on an intention-to-treat basis. FINDINGS: At 5 years the groups differed in terms of the primary composite endpoint of death, myocardial infarction, or both (invasive 217, 19.9 %; noninvasive 270, 24.5 %; risk ratio 0.81; 95% CI 0.69-0.95; p=0.009). 5-year mortality was 117 (9.7%) in the invasive group compared with 124 (10.1%) in the noninvasive group (0.95; 0.75 -1.21; p=0.693). Rates of myocardial infarction were 141 (12.9 %) in the invasive and 195 (17.7%) in the non-invasive group (0.73; 0.60-0.89; p=0.002). The benefit of the invasive strategy was confined to male patients, non-smokers, and patients with two or more risk indicators. INTERPRETATION: The 5-year outcome of this trial indicates sustained benefit of an early invasive strategy in patients with non-ST-elevation acute coronary syndrome at moderate to high risk.
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| 28. |
- Lagerqvist, Bo, et al.
(författare)
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Are There Different Effects of Invasive Treatment Between Women and Men During the Acute Stage of Unstable Coronary Artery Disease?
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVES The FRISC II invasive trial compared an early invasive versus a noninvasive strategy concerning death and MI in CAD. This paper deals with the gender perspective in the same study.METHODS There were 749 women and 1708 men included in the study with a mean age of 66 and 64 years in women and men respectively. The patients were randomized to early invasive or noninvasive strategy and to placebo controlled long-term low molecular mass (1mm) heparin ( dalteparin) treatment for 3 months. Coronary angiographies were performed within the first seven days in 96 % and 10 % and revascularisation was performed within the first 10 days in 71 % and 9 % in the invasive and noninvasive groups, respectively.RESULTS Women were older but had less previous infarctions, better left ventricular function and less frequently had elevated troponin-levels. There were more patients with normal coronary arteries and less severe coronary artery lesions amongst the women. Accordingly, less interventions were performed in the female group although, among those who were revascularized, there was. no significant difference in the choice of procedure compared to men. There was no difference in the composite endpoint of MI and death at 12 months amongst women (12.4 vs. 10.5% in the invasive and non-invasive groups respectively) in contrast to the very favorable effect of the invasively treated group amongst the men (9.6 vs. 15.8%, p<0.001). In a multivariate interaction analysis there was different effect of early invasive strategy in the two genders (p=0.008)CONCLUSIONS Women with symptoms and/or signs of unstable coronary artery disease are older but still have less severe CAD and a better prognosis than men. In contrast to men, an early invasive strategy did not reduce the risk for future events amongst women. Further research is warranted to identify the most appropriate treatment strategy in women with unstable CAD.
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| 29. |
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| 30. |
- Landegren, Nils, et al.
(författare)
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A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:51
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Tidskriftsartikel (refereegranskat)abstract
- Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglutaminase 1 (TGM1) as a member of a protein family prone to autoimmune attack. By screening sera from patients with various acquired skin disorders, we identified seropositive subjects with the blistering mucocutaneous disease paraneoplastic pemphigus. Validation in further subjects confirmed TGM1 autoantibodies as a 55% sensitive and 100% specific marker for paraneoplastic pemphigus. This gene-centric approach leverages the wealth of data available for human genes and may prove generally applicable for biomarker discovery in autoimmune diseases.
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| 31. |
- Leijon, Matti, 1970-, et al.
(författare)
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Is there a demand for physical activity interventions from health care providers? : Findings from a population survey
- 2010
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10:34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care providers in many countries have delivered interventions to improve physical activity levels among their patients. Thus far, less is known about the population's interest to increase their physical activity levels and their opinion about the health care provider's role in physical activity promotion. The aims of this paper were to investigate the self-reported physical activity levels of the population and intention to increase physical activity levels, self-perceived need for support, and opinions about the responsibilities of both individuals and health care providers to promote physical activity.Methods: A regional public health survey was mailed to 13 440 adults (aged 18-84 years) living in Östergötland County (Sweden) in 2006. The survey was part of the regular effort by the regional Health Authorities.Results: About 25% of the population was categorised as physically active, 38% as moderately active, 27% as somewhat active, and 11% as low active. More than one-third (37%) had no intentions to increase their physical activity levels, 36% had thought about change, while 27% were determined to change. Lower intention to change was mainly associated with increased age and lower education levels. 28% answered that physical activity was the most important health-related behaviour to change "right now" and 15% of those answered that they wanted or needed support to make this change. Of respondents who might be assumed to be in greatest need of increased activity (i.e. respondents reporting poor general health, BMI>30, and inactivity) more than one-quarter wanted support to make improvements to their health. About half of the respondents who wanted support to increase their physical activity levels listed health care providers as a primary source for support.Conclusion: These findings suggest that there is considerable need for physical activity interventions in this population. Adults feel great responsibility for their own physical activity levels, but also attribute responsibility for promoting increased physical activity to health care practitioners.
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| 32. |
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| 33. |
- Marcus, Lars, 1962-, et al.
(författare)
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Architectural Knowledge and Complex Urban Space : Analysis of Five Proposals for Slussen in Stockholm
- 2010
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Ingår i: Journal of Space Syntax. - 2044-7507. ; 1:1, s. 177-198
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents, compares and evaluates five design proposals for remodelling the famous, or as some would say infamous, Slussen transport interchange in the Swedish capital, Stockholm. Slussen is strategically located where the locks between Lake Mälaren and the Baltic Sea meet the land bridge between northern and southern Sweden. It is now a major hub for Stockholm's road, bus, boat, rail and underground transport systems, which in 1935 was redesigned as integrated transport node in the modernist style. This has now become so physically deteriorated and obsolete that a series of proposals were put forward during the opening years of the new millennium for its complete remodelling. As a contribution to that exercise, the urban design practice Spacescape was commissioned to analyse and evaluate the likely performance of the various regeneration proposals for Slussen, using methodologies based on space syntax theory and other methods, in order to predict the likely outcome of each proposal on Stockhlom's urban life. In what follows, projects by Atelier Nouvel and Habiter Autrement, Big, Foster and Partners and Berg, Nyréns and finally Wingårdh and Tema have been compared and evaluated in the light of the goals set out in Stockholm's comprehensive city plan.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Marcus, Lars, 1962, et al.
(författare)
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Spacescape – urban research and design
- 2016
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Ingår i: The changing shape of practice. - : Routledge. ; , s. 155-166
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Mistegård, Josephine, et al.
(författare)
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Comorbidities in a Cohort of 66 Patients With Psoriatic Arthritis Mutilans-Results From the Nordic PAM Study
- 2021
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Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis due to excessive bone erosion causing joint destruction and decreased functional capacity. The aim of this study was to investigate the prevalence of comorbidities among patients with PAM and the association between comorbidities and joint involvement.Methods: A total of 66 patients aged >= 18 years from the Nordic countries with past or present psoriasis along with at least one mutilated joint were included in the present study.Results: The median number of comorbid conditions per patient was 1 [interquartile range (IQR) 0-2] and 16.7% reported three or more comorbidities. The most frequent comorbidity was hypertension (36.4%). The median number of mutilated joints per patient was 3 (IQR 1-8.3; range 1-38).Conclusion: Two thirds of the patients with PAM reported comorbid conditions and the most frequent was hypertension which affected more than a third of the patients. However, this study was unable to detect any association between comorbidities and the severity of PAM.
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| 45. |
- Myrdal, Gunnar, et al.
(författare)
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Regional differences in treatment and outcome in non-small cell lung cancer : a population-based study (Sweden)
- 2009
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 63:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- In the recent decade uniform treatment guidelines for non-small cell lung cancer (NSCLC) have been introduced in Sweden. The objective of this study was to examine time trends and differences in treatment intensity for NSCLC between county clinical centres in Central Sweden. A second aim was to investigate whether any differences in treatment of NSCLC were associated with differences in survival. 4345 patients with a diagnosis of NSCLC between 1995 and 2003 were identified in the population-based Lung Cancer Register of Central Sweden. Multivariate logistic regression was used to estimate odds ratios to analyse the likelihood of receiving different treatment modalities for NSCLC. Cox proportional hazard models estimating relative hazard ratios were used to identify factors related to death (by any cause). Of all patients, 33.4% received no treatment, and 17.5% underwent surgery. Between 1995 and 2003, the proportion of patients receiving chemotherapy rose from 14.6% to 55%. There were pronounced differences between county centres in treatment policies, especially concerning surgery and radiotherapy. The likelihood of receiving treatment for NSCLC was highest at county centre A where both surgical treatment and chemotherapy were given more often. Compared to this reference county, the risk of death was between 20% and 40% higher in the other counties after adjusting for age, stage, gender, time period, smoking status and histopathological type. When analyses were adjusted for treatment, county of residence was no longer a prognostic factor. Despite common guidelines there were marked differences in treatment activity between the counties. Treatment activity was associated with survival. Survival benefits may follow improvement in compliance to guidelines.
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| 46. |
- Nordmark, Anna, et al.
(författare)
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Assessment of interaction potential of AZD2066 using in vitro metabolism tools, physiologically based pharmacokinetic modelling and in vivo cocktail data
- 2014
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 70:2, s. 167-178
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Static and dynamic (PBPK) prediction models were applied to estimate the drug-drug interaction (DDI) risk of AZD2066. The predictions were compared to the results of an in vivo cocktail study. Various in vivo measures for tolbutamide as a probe agent for cytochrome P450 2C9 (CYP2C9) were also compared.METHODS: In vitro inhibition data for AZD2066 were obtained using human liver microsomes and CYP-specific probe substrates. DDI prediction was performed using PBPK modelling with the SimCYP simulator™ or static model. The cocktail study was an open label, baseline, controlled interaction study with 15 healthy volunteers receiving multiple doses of AD2066 for 12 days. A cocktail of single doses of 100 mg caffeine (CYP1A2 probe), 500 mg tolbutamide (CYP2C9 probe), 20 mg omeprazole (CYP2C19 probe) and 7.5 mg midazolam (CYP3A probe) was simultaneously applied at baseline and during the administration of AZD2066. Bupropion as a CYP2B6 probe (150 mg) and 100 mg metoprolol (CYP2D6 probe) were administered on separate days. The pharmacokinetic parameters for the probe drugs and their metabolites in plasma and urinary recovery were determined.RESULTS: In vitro AZD2066 inhibited CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP2D6. The static model predicted in vivo interaction with predicted AUC ratio values of >1.1 for all CYP (except CYP3A4). The PBPK simulations predicted no risk for clinical relevant interactions. The cocktail study showed no interaction for the CYP2B6 and CYP2C19 enzymes, a possible weak inhibition of CYP1A2, CYP2C9 and CYP3A4 activities and a slight inhibition (29 %) of CYP2D6 activity. The tolbutamide phenotyping metrics indicated that there were significant correlations between CLform and AUCTOL, CL, Aemet and LnTOL24h. The MRAe in urine showed no correlation to CLform.CONCLUSIONS: DDI prediction using the static approach based on total concentration indicated that AZD20066 has a potential risk for inhibition. However, no DDI risk could be predicted when a more in vivo-like dynamic prediction method with the PBPK with SimCYP™ software based on early human PK data was used and more parameters (i.e. free fraction in plasma, no DDI risk) were taken into account. The clinical cocktail study showed no or low risks for clinical relevant DDI interactions. Our findings are in line with the hypothesis that the dynamic prediction method predicts DDI in vivo in humans better than the static model based on total plasma concentrations.
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| 47. |
- Salehpour, Mehran, et al.
(författare)
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Biological Accelerator Mass Spectrometry at Uppsala University
- 2009
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Ingår i: Applied Radiation and Isotopes. - : Elsevier BV. - 0969-8043 .- 1872-9800. ; 67:3, s. 495-499
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Tidskriftsartikel (refereegranskat)abstract
- A new research programme for the biological applications of accelerator mass spectrometry has been initiated at Uppsala University and the first results are presented. A C-14-labelled pharmaceutical substance has been dissolved in human blood, plasma and urine and diluted over 3 orders of magnitude. The measured drug concentrations were found to be in good agreement with the predicted values. Furthermore, the effect of the sample preparation background contribution has been studied as the sample amount was varied down to sub-mu l sizes.
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| 48. |
- Sandberg Hiltunen, Maria, 1966-
(författare)
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Deciphering sequence data : A multivariate approach
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, attention has been focused on the quantitative description of nucleic acids, proteins and peptides. The strategy was to use multivariate chemometrical methods for improving the understanding of the complex structural codes of these kinds of biological molecules. Tools have been developed that enable quantitative modelling of biological molecules, i.e. models based on data that quantitatively describes their properties. The advantage of such models is that they provide interpretations in terms of chemical characteristics for complex features such as similarity, dissimilarity and potency.By a multivariate physical-chemical characterization of the building blocks of nucleic acids and proteins, i.e. nucleosides and amino acids, descriptive scales have been developed, so called principal properties. The scales give a description of the intrinsic properties of these building blocks. The multivariate characterization results in a multi-property matrix. A principal component analysis of the multi-property matrix gives a small number of latent variables which are considered as the principal properties of the characterized molecules.The principal property scales may be used for a wide range of different purposes, such as detecting trends and groupings in large sequence data sets, and for analyzing quantitative relationships between structure and function. In statistical experimental design, the descriptors are well suited as design variables to select combinations of amino acids in such a way that they span a wide range of properties.The use of these principal property descriptors is demonstrated in the quantitative modelling of relationships between structure and activity of various peptide series, DNA-promoters and in the quantitative modelling of transfer ribonucleic acid sequence data (tRNA).
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| 49. |
- Sandström, Eric, et al.
(författare)
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Antiretroviral treatment of human immunodeficiency virus infection: Swedish recommendations
- 2003
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Ingår i: Scand J Infect Dis. - : Informa UK Limited. ; 35:3, s. 155-67
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Forskningsöversikt (refereegranskat)abstract
- The Swedish guidelines (SwG) for treatment of human immunodeficiency virus (HIV) infection have several important roles. A major task involves the promotion of a uniformly high standard of care in all HIV treatment clinics in Sweden and the identification of strengths, weaknesses and relevance of recent research findings. CD4+ T-cell counts < 200 cells/microl are clear indications for the initiation of treatment, whereas high viral loads serve as an indication for increased vigilance rather than a criterion for therapy. It is recommended that the first regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with 1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor. The definition of treatment failure is rigorous. Treatment change should be considered if the viral load has not fallen by at least 1.5 log in 4 weeks or is undetectable within 3-4 months. Resistance testing is endorsed at primary infection, in the event of treatment failure and in pregnant women. Interaction with experts in HIV resistance testing is emphasized. Therapeutic drug monitoring is advocated. Patients with treatment failure should be handled individually and the decision on therapeutic strategy should be based on treatment history, resistance testing and other clinical facts. The SwG do not give recommendations for some important issues such as prolonged drug holidays and preferences in initial treatment regimens. More scientific data are likely to be available soon and the SwG will be refined accordingly. The present guidelines are translated from Swedish; they are published on the Medical Products Agency (MPA) and Swedish Reference Group for Antiviral Therapy (RAV) websites (www.mpa.se and www.rav.nu.se), including 7 separate papers based on a thorough literature search. A complete reference list is available on request from the MPA.
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