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- Äbelö, Angela, et al.
(författare)
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Pharmacodynamic modelling of reversible gastric acid pump inhibition in dog and man
- 2001
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Ingår i: European Journal of Pharmaceutical Sciences. - 0928-0987 .- 1879-0720. ; 14:4, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- H 335/25, a 4-amino quinoline, belongs to a new class of reversible gastric acid pump inhibitors. A potential advantage of such drugs over the irreversible proton pump inhibitors (PPIs) is better control over the effect-time profile. Dose escalation studies were performed to characterize the effect on acid secretion in dogs (n=24) and healthy male subjects (n=12). The effect-time profile was delayed compared to the concentration-time profile. A model-based approach, using non-linear mixed effects modelling, was applied to quantify and elucidate the mechanism for the delayed effect. Three different models were investigated: (1) a slow equilibration preceding the formation of drug-enzyme complex, modelled by an effect-compartment, (2) a slow equilibration between free drug, free enzyme and drug-enzyme complex, described by a kinetic binding model, and (3) a delay between enzyme inhibition and the measured response, described by an indirect response model. Model 2 was shown to be superior to models 1 and 3, for both dog and human data. The dissociation rate constant, k(off), was estimated to be 0.85 and 0.88 h and the calculated equilibration constant, K(d), was 160 and 250 nM in dog and man, respectively. Simulations of the predicted time-course of the effect beyond the 4-5-h observation period was similar for the three models.
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| 5. |
- Dahlstedt, Åsa G., et al.
(författare)
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Market-driven requirements engineering processes for software products - a report on current practices
- 2003
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Konferensbidrag (refereegranskat)abstract
- This paper reports on some preliminary results from the first stage of an interview survey, focusing on current practices and challenges in market-driven RE. The interviews are analysed based on the characteristics of market-driven RE presented in the literature. The interviews correspond largely with the literature. Identified discrepancies compared with the literature concerns the time-to-market attribute and documentation of requirements. Two major groupings among the participating companies were found. The RE processes of one of these groupings are focused on facilitating the activities fundamental in market-driven RE, e.g. the release planning activity, while the other is more document-driven. The results of the interviews also include some ideas on how market-driven RE activities may be performed.
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| 6. |
- Gelin, Johan, 1948, et al.
(författare)
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Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.
- 2001
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Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 22:2, s. 107-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. Design: prospective, randomised study. METHODS: a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis. RESULTS: invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure. CONCLUSION: invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.
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| 7. |
- Herlitz, Johan, et al.
(författare)
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Improvement and factors associated with improvement in quality of life during 10 years after coronary artery bypass grafting
- 2003
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Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 14:7, s. 509-517
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe (1) the improvement in various aspects of quality of life (QoL) and (2) predictors of improvement, during 10 years after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: All patients who underwent CABG in western Sweden between June 1988 and June 1991 without simultaneous valve surgery and with no previous CABG were approached with an inquiry prior to and 5 and 10 years after the operation. QoL was measured with three different instruments: (1) Nottingham health profile (NHP), (2) psychological general well-being index (PGWBI) and (3) physical activity score (PAS). RESULTS: There was a significant improvement in QoL with all three instruments from before to 10 years after the operation. The mean improvements +/-SD were for NHP, - 4.2+/-17.0 (P<0.0001), for PGWBI, +9.7+/-17.6 (P<0.0001) and for PAS, -0.96+/-1.23 (P<0.0001). However, there was also a deterioration with all three instruments between 5 and 10 years after surgery. The mean deteriorations +/-SD were for NHP, +4.4+/-12.8 (P<0.0001), for PGWBI, -4.6+/-14.8 (P<0.0001) and for PAS, +0.44+/-0.94 (P<0.0001). Independent predictors for an improvement in QoL with at least one of the instruments were low preoperative QoL, a younger age, being a man, high functional class (New York Heart Association), no hypertension, proximal left anterior descending coronary artery stenosis, short extracorporeal circulation time, use of internal mammary artery and a short postoperative time in the intensive care unit. CONCLUSION: There is a higher estimated QoL 10 years after CABG than before, despite the fact that the patients are 10 years older. However, there is also a deterioration in QoL between 5 and 10 years after surgery. Predictors of improvement during the 10 years included age, sex, previous history, localization of stenosis, type of graft and preoperative and postoperative factors.
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| 8. |
- Herlitz, Johan, et al.
(författare)
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Limitation of physical activity, dyspnea and chest pain prior to and two years after coronary artery bypass grafting in relation to preoperative ejection fraction
- 2000
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa Healthcare. - 1401-7431 .- 1651-2006. ; 34:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the relationships between limitation of physical activity and dyspnoea and chest pain before and 2 years after coronary artery bypass grafting (CABG) and preoperative left ventricular ejection fraction (LVEF), questionnaires were issued to all patients from Western Sweden who underwent CABG during 1988-1991. The analysis comprised 985 patients. Physical activity improved significantly after CABG regardless of the preoperative LVEF. No significant association was found between LVEF and degree of limitation of physical activity before or after surgery. Dyspnoea and chest pain improved markedly, irrespective of LVEF. There was significant association between freedom from dyspnoea and LVEF preoperatively (less dyspnoea with higher LVEF), but not after CABG. The frequency of chest-pain attacks was not related to LVEF, before or after the operation. Thus physical activity, dyspnoea and chest pain improved in the 2 years after CABG irrespective of preoperative LVEF. Absence of dyspnoea was related to LVEF before, but not after surgery, and there was no association between preoperative LVEF and frequency of anginal attacks before or after CABG.
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| 9. |
- Herlitz, Johan, et al.
(författare)
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Long term prognosis after CABG in relation to preoperative left ventricular ejection fraction
- 2000
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Ingår i: International Journal of Cardiology. - : Elsevier Ireland Ltd. - 0167-5273 .- 1874-1754. ; 72:2, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate the mortality rate, risk indicators for death, mode of death and symptoms of angina pectoris during 5 years after coronary artery by pass grafting (CABG) in relation to the preoperative left ventricular ejection fraction (LVEF). PATIENTS: All patients in western Sweden who underwent CABG without concomitant valve surgery and without previously performed CABG between June 1988 and June 1991. RESULTS: In all 1904 patients were included in the analysis, of whom 173 (9%) had a LVEF < 40%. Patients with LVEF > or = 40% had a 5-year mortality of 12.5%. LVEF < 40% was associated with an increased risk of death (RR 2.3; 95% cl 1.7-3.1). There was no significant interaction between age, sex or any other factor in terms of clinical history and LVEF. However, left main stenosis was a strong independent predictor of death among patients with LVEF < 40% but not in those with a higher LVEF. Patients with a low LVEF more frequently died a cardiac death and a death associated with myocardial infarction (AMI). Furthermore they more frequently died in association with congestive heart failure and ventricular fibrillation. Among survivors, symptoms of angina pectoris were similar regardless of the preoperative LVEF. CONCLUSION: Patients with a low preoperative LVEF have a more than two-fold increased risk of death during 5 years after CABG. Their increased risk of death includes cardiac death, death associated with AMI, congestive heart failure and ventricular fibrillation.
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| 10. |
- Herlitz, Johan, et al.
(författare)
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Mortality, mode of death and risk indicators for death during 5 years after coronary artery bypass grafting among patients with and without a history of diabetes mellitus
- 2000
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Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 11:4, s. 339-346
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe mortality, mode of death, risk indicators for death and symptoms of angina pectoris among survivors during 5 years after coronary artery bypass grafting (CABG) among patients with and without a history of diabetes mellitus. METHODS: All patients in western Sweden who underwent CABG without concomitant valve surgery and who had no previous CABG between June 1988 and June 1991 were entered prospectively in this study. After 5 years, information on deaths that had occurred was obtained for the analysis. RESULTS: In all, 1998 patients were included in the analysis; 242 (12%) had a history of diabetes. Among the non-diabetic patients, 5-year mortality was 12.5%; the corresponding relative risk for diabetic patients was 2.1 (95% confidence interval 1.6 to 2.9). A history of diabetes was an independent risk indicator of death; there was no significant interaction between any other risk indicator and diabetes. Independent risk indicators for death among diabetic patients were: current smoking, renal dysfunction and left ventricular ejection fraction < 0.40. Compared with non-diabetic patients, those with diabetes more frequently died in hospital, died a cardiac death, or had death associated with the development of acute myocardial infarction and with symptoms of congestive heart failure. Among survivors, diabetic patients tended to have more angina pectoris 5 years after CABG than did those without diabetes. CONCLUSION: During a period of 5 years after CABG, diabetic patients had a mortality twice that of non-diabetic patients. The increased risk included death in hospital, cardiac death and death associated with development of acute myocardial infarction and with symptoms of congestive heart failure.
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