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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European radiology 8 (1998), S. 484-487 
    ISSN: 1432-1084
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 150 (1991), S. 214-216 
    ISSN: 1432-1076
    Keywords: Daycare ; Common cold ; Wheezy bronchitis ; Otitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The health hazards of daycare attendance for the development of upper and lower respiratory tract infections have been well documented; however the importance and the mechanism of this association have not been well defined. In order to ascertain the risk associated with the beginning of daycare (DC) attendance we conducted a survey on 1263 children aged from 3 months to 3 years; the analysis focused on the risk of developing an initial episode of common cold with fever, a first otitis and a first wheezy bronchitis (WB) within the 2 month period following adminission to DC. For each 2 month period, the risk of a first infectious event was much higher in children who had just begun attending DC than in children who remained at home: the risk ratio varied from 1.7 to 2.4 for common cold, from 1.5 to 1.9 for otitis and from 1.8 to 3.2 for WB. Because age at onset of the first infectious event may be related to a higher risk of repeated events we consider that admission to DC under 12 months of age should be quesioned.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 333-336 
    ISSN: 1432-1041
    Keywords: anticoagulants ; myocardial infarction ; randomized control trials ; pooled data ; odds ratio test ; long-term oral anticoagulants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Evidence of the preventive efficiency of long term oral anticoagulant (OA) therapy after myocardial infarction (MI) is still controversial. In an attempt to reappraise this problem, a study has been undertaken using the odds ratio method in which the data from 7 published studies of long term OA therapy after MI were pooled. The studies selected met predefined quality standards. The combination of the studies provided a sample of 1284 patients in the OA group versus 1013 in the reference group. The total mortality rates were 20.73% in the control group and 17.99% in the OA group; the difference is significant atp=0.05. For recurrent MI only 5 trials could be pooled. The reinfarction rates were 13.81% in the control group versus 10.25% in the OA group, and again the difference is significant. The interpretation of such reassessed data is subject to certain limitations.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 335-336 
    ISSN: 1432-1041
    Keywords: Pre-injection period changes ; inotropic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 177-182 
    ISSN: 1432-1041
    Keywords: Pinacidil ; Pharmacodynamic model ; effect-compartment model ; potassium channel activator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration-effect relationships of pinacidil, a peripheral vasodilator, have been measured in 12 healthy adults who received placebo or pinacidil 25 mg daily for 1 week in a cross-over experiment. Diastolic blood pressure (DBP) and heart rate (HR) were recorded and blood samples were taken on days 1 and 7. Plasma drug concentration-time data were fitted by a biexponential function with zero-order input. The pharmacokinetic model was incorporated into a combined pharmacokinetic-dynamic model (PK-PD) using the Hill equation, which has three parameters: n, the sigmoidicity parameter, Emax the maximum effect and EC50 the concentration which gives 50% of Emax. For ΔDBP, the parameter medians were estimated as n=5, EC50=44.6 ng · ml−1 and Emax=13.5 mm Hg. A hysteresis loop was found when ΔHR was plotted against concentration, which could be fitted by a linear effect compartment model. Simulations showed that experimental ΔDBP points on Day 7 could be predicted from a simulated curve computed by the model using parameters estimated on Day 1. Using the simulation, it was possible to suggest an optimal dosage regimen for pinacidil tablets.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: Phosphodiesterase inhibitors ; Mortality ; meta-analysis ; chronic heart failure ; vasodilator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We examined the influence of phosphodiesterase inhibitors (PDIs) on mortality in patients with overt chronic heart failure. A total of 13 randomised, placebocontrolled trials of PDIs involving 2808 patients were selected. Meta-analysis, using data for all patients, showed that there was a non-significant (P=0.16) increase of about 17% in the mortality rate of patients receiving a PDI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.94–1.46]. However, the observed treatment effects were found to be heterogeneous due to the results from the trials on vesnarinone. The heterogeneity became non-significant (P=0.77) when these trials were removed, and a significant increase in the mortality rate was observed under treatment with the other PDIs (OR 1.41, 95% CI 1.11–1.79). In the subgroups of patients with or without additional vasodilator (VD) treatment, similar results were observed (PDI with VD: OR 1.3, 95% CI 1.03–1.7; PDI without VD: OR 2.04, 95% CI 1.1–3.8). These results indicate that PDIs (with the exception of vesnarinone) should not be prescribed for long-term use in patients with overt chronic heart failure. Additional vasodilator treatment in patients receiving PDIs for chronic heart failure does not explain the increased mortality seen with PDIs. This toxicity must, therefore, arise by other mechanisms. Further experimental and clinical evaluation is needed to confirm the beneficial influence of vesnarinone on survival in chronic heart failure patients and to identify the mechanism(s) differentiating this agent's therapeutic effect from that of other PDIs.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: Key words Nicardipine ; Hypertension; slow release formulation ; compliance ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objectives: To compare compliance with an antihypertensive treatment administered either twice daily or three times daily. The two formulations of the antihypertensive treatment used (nicardipine) “regular tablets” (t.d.) and “slow release tablets” (b.d.) are bioequivalent at the daily dosage used in the study. Study design: Open, controlled, parallel designed study with centralised, randomised allocation to the treatment groups: TID group: A nicardipine 20 mg tablet, three times daily for 3 months. BID group: A capsule of slow release (SR) nicardipine, 50 mg twice daily for 3 months. Patients: 7274 hypertensive patients were investigated by 2.651 general practitioners. Compliance with the nicardipine was assessed by means of standardised interviews with the patients and by a questionnaire for the investigators. Results: Compliance was slightly higher in the BID than in the TID group; 71.2% and 24.5% of patients in the first group declared their compliance was 100% and 80% compared to 82.3% and 15% in the second group. A statistically significant relationship was shown between compliance with nicardipine and the decrease in blood pressure after three months of therapy. However, no significant difference was noticed between the two groups of patients in the absolute decrease in blood pressure after the treatment period: 25.7/14.7 mm Hg in the TID group compared with 25.9/15.0 mm Hg in the BID group. Conclusions: A difference in compliance between the bioequivalent BID and TID formulations of the same active agent was shown in hypertensive patients. However, the difference was not large enough to lead to a difference either in the number of controlled patients or in the decrease in blood pressure. Reducing the number of daily doses does not automatically lead to greater efficacy of treatment.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1987), S. 559-562 
    ISSN: 1432-1041
    Keywords: systole ; inotropic activity ; pharmacodynamic screening ; mexelitine ; disopyramide ; healthy volunteers ; pre-ejection period
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Since heart rate (HR) is an important determinant of the duration of systole, systolic time intervals (STI) from 8 healthy subjects were examined after infusion of atropine. As no overall correlation was found between HR and pre-ejection period (PEP), the results confirm the need for individual estimates of the correction of the left ventricular ejection time (LVET) and the total electromechanical systole (OS2). In the same subjects the sensitivity of PEP to minor negative inotropic effects of mexiletine and disopyramide measured at Cmax was confirmed. Thus, in addition to its simplicity and reliability, the sensitivity of the uncorrected PEP should encourage use of this technique as part of any screening system for the early detection of an inotropic effect of new chemical entities.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 527-529 
    ISSN: 1432-1041
    Keywords: pinacidil ; vasodilatation ; plethysmography ; calf blood flow ; hypotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The hypotensive and peripheral vascular effects of two different oral formulations of pinacidil were investigated in twelve healthy male volunteers. Arterial blood pressure, heart rate and calf blood flow were measured on Days 1 and 7. The vasodilator activity of both formulations was confirmed by a significant increase in calf blood flow on both days, which was correlated with a significant decrease in diastolic blood pressure. There was no differences between the tablet and the pellet.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 43 (1992), S. 235-244 
    ISSN: 1432-1041
    Keywords: Surrogate endpoints ; Clinical trials ; risk/benefiratio ; assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In clinical trials, the clinical endpoint is often replaced by an intermediate endpoint, known in some instances as a “surrogate” endpoint. The reasons for the substitution are often both practical and financial. At present, no theoretical basis or practical guidelines exist to help in the choice of surrogate endpoints. An approach is proposed here, based on three provisos which can be verified using one of a series of equations, if sufficient data on the pathophysiology and epidemiology of the disease are available. It is shown that even a strong statistical correlation is not a sufficient criterion for the definition of a surrogate endpoint. It is apparent that results obtained with the commonly used “surrogate” endpoints should be cautiously considered and that the assessment of treatments should, when possible, be based on clinical rather than intermediate endpoints.
    Type of Medium: Electronic Resource
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