| 1. |
- Khoshnood, Ardavan
(författare)
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Prehospital Diagnosis and Oxygen Treatment in ST Elevation Myocardial Infarction
- 2017
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Doktorsavhandling (övrigt vetenskapligt)abstract
- IntroductionPaper I: An Artificial Neural Network (ANN) was constructed to identify ST Elevation Myocardial Infarction (STEMI) and predict the need for Percutaneous Coronary Intervention (PCI). Paper II, III and IV: Studies suggest that O2 therapy may be harmful in STEMI patients. We therefore conducted the SOCCER study to evaluate the effects of O2 therapy in STEMI patients.MethodsPaper I: 560 ambulance ECGs sent to the Cardiac Care Unit (CCU), was together with the CCU physicians interpretation and decision of conducting an acute PCI or not collected, and compared with the interpretation and PCI decision of the ANN. Paper II, III, IV: Normoxic (≥94%) STEMI patients accepted for acute PCI were in the ambulance randomized to standard care with 10 L/min O2 or room air. A subset of the patients underwent echocardiography for determination of the Left Ventricular Ejection Fraction (LVEF) and the Wall Motion Score Index (WMSI). All patients had a Cardiac Magnetic Resonance Imaging (CMRI) to evaluate Myocardial area at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI).ResultsPaper I: The area under the ANN’s receiver operating characteristics curve for STEMI detection as well as predicting the need of acute PCI were very good.Paper II, III, IV: No significant differences could be shown in discussing MaR, MSI or IS between the O2 group (n=46) and the air group (n=49). Neither could any differences be shown for LVEF and WMSI at the index visit as well after six months between the O2 group (n=46) and the air group (n=41)ConclusionsPaper I: The results indicate that the number of ECGs sent to the CCU could be reduced with 2/3 as the ANN would safely identify ECGs not being STEMI.Paper II, III, IV: The results suggest that it is safe to withhold O2 therapy in normoxic, stable STEMI patients.
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| 2. |
- Lind, Marcus, et al.
(författare)
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Thrombomodulin as a marker for bleeding complications during warfarin treatment
- 2009
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 169:13, s. 1210-1215
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The major adverse effect of warfarin treatment is hemorrhage. Several risk factors for bleeding complications are also risk factors for thromboembolic events, making the clinical decision to initiate or withhold anticoagulant treatment difficult. Specific markers that solely identify patients at high risk of bleeding would have great clinical impact. This study aimed to test if thrombomodulin (TM) concentrations were associated with bleeding complications, cardiovascular events, or mortality in long-term anticoagulant-treated patients. METHODS: In a longitudinal cohort study we followed up 719 patients receiving warfarin treatment for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified. Soluble TM antigen (sTM) concentration in plasma was measured with an enzyme-linked immunosorbent assay method. RESULTS: During the follow-up time, 113 clinically relevant bleeding events and 73 major bleeding events occurred. Increased concentration of sTM was associated with both clinically relevant bleeding and major bleeding events after adjustment for age. In the multivariable models, hazard ratios for the highest tertiles compared with the lowest were 2.29 (95% confidence interval, 1.35-3.89) and 2.33 (95% confidence interval, 1.21-4.48), respectively. No association between sTM concentration and nonfatal ischemic cardiovascular events or all-cause mortality was found. CONCLUSIONS: Increased levels of sTM are associated with bleeding complications during warfarin treatment but not with cardiovascular events or all-cause mortality. Soluble TM antigen concentration has potential as a new specific marker to identify patients at high risk of bleeding during warfarin treatment.
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| 3. |
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| 4. |
- Greiff, Lennart, et al.
(författare)
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Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
- 1997
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Ingår i: Acta Physiologica Scandinavica. - : Wiley-Blackwell. - 0001-6772. ; 160:4, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
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| 5. |
- Magnusson, Marie, et al.
(författare)
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A placebo-controlled study of retinal blood flow changes by pentoxifylline and metabolites in humans
- 2006
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 61:2, s. 138-147
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the possible effects of pentoxifylline metabolites on retinal blood flow in humans. METHODS: A randomized, placebo-controlled, four-period cross-over study that was observer blinded and partly blinded for the eight participants. On one occasion a placebo was given as an intravenous (i.v.) infusion over 100 min. On the other three occasions pentoxifylline was administered as i.v. infusions over 100 min at a rate of 3 mg min(-1). Before two of the pentoxifylline infusions the subjects were pretreated with either ciprofloxacin or rifampicin. Retinal blood flow was measured by scanning laser doppler flowmetry (SLDF) in a selected area of the central temporal retina before, during and until 5 h after the end of infusion. Blood samples for concentration analyses of pentoxifyllin, R-M1, S-M1, M4 and M5 were taken serially and areas under the curves (AUCs) were calculated. Linear mixed models were used for the statistical analyses. RESULTS: Mean AUCs (ng h ml(-1)) were significantly increased for pentoxifylline (1964 vs. 1453) and S-M1 (5804 vs. 4227), but not R-M1 when pentoxifylline was co-administered with ciprofloxacin. The mean AUC for M5 was significantly reduced when subjects were pretreated with rifampicin (2041 vs. 3080). Pentoxifylline with and without pretreatment with rifampicin significantly increased retinal blood flow assessed as mean flow, pulsation (i.e. 1-systole/diastole), and diastolic flow (but not during systole), compared with placebo. The increases over placebo were more pronounced on diastolic flow, 9.7% (95% confidence interval 4.2, 15.5) than on mean flow, 4.6% (1.1, 8.3) after pentoxifylline administration. With pentoxifylline after rifampicin pretreatment the corresponding differences were 11.7% (5.8, 17.9) and 5.1% (1.4, 7.8) over placebo, respectively. After co-administration of pentoxifylline and ciprofloxacin we saw only a nonsignificant trend towards increased flow during diastole, but a significant decrease in pulsation. When AUCs for pentoxifylline and its metabolites were used as regressor variables to retinal mean flow we found that pentoxifylline, R-M1 and M5 had coefficients with a positive sign indicating that they enhanced the retinal blood flow. In contrast, S-M1 and M4 had coefficients with negative sign and thus appeared to decrease the blood flow in subjects treated with pentoxifylline. CONCLUSION: The R-M1 and M5 metabolites of pentoxifylline contributed significantly to the effects of pentoxifylline on retinal blood flow.
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| 6. |
- Saulo, Eleonor C., et al.
(författare)
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Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
- 2008
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Ingår i: Malaria Journal. - London : BioMed Central. - 1475-2875 .- 1475-2875. ; 7, s. 227-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.MethodsStructured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.ResultsAmong 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.ConclusionWTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.
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| 7. |
- Brattström, L, et al.
(författare)
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Pyridoxine reduces cholesterol and low-density lipoprotein and increases antithrombin III activity in 80-year-old men with low plasma pyridoxal 5-phosphate
- 1990
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa Healthcare. - 1502-7686 .- 0036-5513. ; 50:8, s. 873-877
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Tidskriftsartikel (refereegranskat)abstract
- We have previously observed that pyridoxine treatment reduced plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations and increased antithrombin III (AT III) activity in atherosclerotic patients with subnormal plasma pyridoxal 5-phosphate (PLP) levels. In order to confirm these results, we selected 17 males with low plasma PLP levels from a group of 122 80-year-old males in whom PLP has been determined. After supplementation with 120 mg of pyridoxine per day for 8 weeks their mean plasma TC and LDL cholesterol concentrations were decreased by 10% (p less than 0.01) and 17% (p less than 0.001), respectively. There was no effect on high-density lipoprotein cholesterol and triglycerides but plasma AT III activity was increased by 6% (p less than 0.05). The mechanism by which pyridoxine acts is unclear but it is hypothesized that pyridoxine-derived PLP may enhance the catabolism of LDL and the activity of AT III by inhibiting their glycosylation.
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| 8. |
- Persson, Carl, et al.
(författare)
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Unbalanced research
- 2001
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Ingår i: Trends in Pharmacological Sciences. - : Elsevier. - 0165-6147. ; 22:10, s. 538-541
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Nilsson, Bengt-Olof, et al.
(författare)
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Effects of polyamine synthesis inhibition on polyamines, growth and mechanical properties in hypertrophic rat urinary bladder
- 1998
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Ingår i: Pharmacology and Toxicology. - : Wiley-Blackwell. - 1600-0773. ; 82:6, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- The polyamines putrescine, spermidine and spermine, are ubiquitous intracellular metabolites associated with growth and protein synthesis. In this study effects of polyamine synthesis inhibition on bladder growth, polyamine levels and mechanical properties were investigated in rat urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibitor CGP-48664 (5 and 20 mg kg-1) was administered alone or in combination with the ornithine decarboxylase inhibitor DFMO (500 mg kg-1), starting one day before creation of partial outflow obstruction and then daily for 7 days. The bladder muscle level of putrescine was increased 38 times and that of spermine reduced by 4 times while spermidine was unchanged after treatment with CGP-48664 (20 mg kg-1). The increase in putrescine was abolished in animals receiving CGP-48664 in combination with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by bladder wet weight and protein contents. The effects on polyamine quantities were not associated with changes in Ca(2+)-force relationship or in agonist and electrically stimulated force. In summary, treatment of rats with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or mechanical properties.
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| 10. |
- Gustavsson, Anders, et al.
(författare)
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Cost of disorders of the brain in Europe 2010.
- 2011
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Ingår i: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
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