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  • 1
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; Bromocriptine ; L-Dopa/benserazide ; early combination therapy ; long-term ; therapy ; mortality ; cardioprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary L-Dopa supplemented by a peripheral decarboxylase inhibitor is considered the most potent therapeutic regimen prolonging active life in Parkinsonian patients. The long-term benefit of therapy is limited by adverse effects, such as dyskinesia and on-off phenomena, which can be mitigated by the concomitant administration of dopamine agonists, such as bromocriptine. In order to quantify the beneficial impact of early combination therapy, a controlled clinical trial (PRADO:PRA vi-del1 +DOpa) in patients with early Parkinson's disease was carried out, whereby L-Dopa monotherapy (in a fixed combination with benserazide (DoBe) was being compared with the same combination plus bromocriptine (DoBeBro). Patients were recruited and treated by 101 practising neurologists in the Federal Republic of Germany and in Hungary. 'Twenty seven clinical university centers cross-checked the patients at regular intervals. The trial started with 3 months of DoBe monotherapy (median dose of 375 mg L-Dopa for both randomized groups) followed by gradual substitution of DoBe by bromocriptine over 3 months in one of the groups (250 mg L-Dopa/10 mg bromocriptine). The target medication was maintained from study months 6 to 54. Parkinsonian symptoms were classified according to the Webster rating scale, the Hoehn and Yahr scale and the Zung Self-Rating Depression Scale. Adverse events and life status were checked at regular intervals. Special emphasis was given to motor performance tests. 587 patients (302 in the DoBe group and 285 in the DoBeBro group) were available for intention-to-treat analysis. Both groups were homogeneous at baseline in all observed parameters. DoBe and DoBeBro proved equi-effective in terms of antiparkinsonian activity after the substitution phase (P II) had been completed. In September 1991, after a median observation period on target medication of 38.4 months in the DoBe group and 40.1 months in the DoBeBro group, 18 versus 8 deaths had been registered. The Logrank test as well as analysis using the Cox model, both adjusted for age and sex, showedP-values of 0.018 and 0.021, respectively. The mortality risk associated with L-Dopa therapy was reduced by more than 50 % by its combination with bromocriptine. The study was terminated due to this difference in mortality. The causes of death were classified by the treating physicians and consultants. At the time of study termination 152 patients in the DoBe group and 121 in the DoBeBro group had already discontinued study medication. Of those further 26 patients had died by the date of the final evaluation, 15 on DoBe and 11 on DoBeBro. The results imply that combination therapy with bromocriptine should be preferred over L-Dopa monotherapy from the very beginning.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 1177-1185 
    ISSN: 1432-1440
    Keywords: Exactitude ; Error coefficients ; Statistical methods for reporting error ; Laboratory tests ; Medical questionnaire ; Accuracy, precision ; Genauigkeit ; Fehlerkoeffizienten ; Statistische Fehlerangaben ; Laboruntersuchungen ; Med. Fragebogen ; Richtigkeit ; Präzision
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Genauigkeit einiger gebräuchlicher Laborverfahren (Triglyceride, Gesamtcholesterin, Glucose, Harnsäure, Kreatinin) wird in einer praxisnahen Situation untersucht und verschiedene statistische Verfahren zur Fehlerangabe werden miteinander verglichen. Richtigkeit und Präzision sind geeignete Maße für die Güte der Analytik. Sie sind für die Beurteilung eines Einzelwertes nicht ausreichend, weil die Einflüsse von Probenentnahmen, Art der Probe, Probentransport und Probenlagerung nicht in die Richtigkeit und Präzision eingehen. Diese Störeinflüsse können die Güte der Analytik weitgehend entwerten. Als weitergreifende Methode für sinnvolle Fehlerangaben von Laborverfahren werden Fehlerkoeffizienten vorgeschlagen, die auf einen varianzanalytischen Ansatz basieren: Gesamtfehler, Technischer Fehler und Transportfehler beim Postversand. In dieser Studie wird deutlich, daß die Fehlerstreuung, die durch den Transport desselben Serums in einer Kühltasche im Auto gegenüber dem regulären Postversand besteht, beträchtlich ist. Sie ist von einer Größenordnung, die eine Beurteilung der Einzelwerte durch den Arzt im Grenzbereich zwischen eindeutig normalen und eindeutig pathologischen Befund unmöglich machen kann. Dies gilt insbesondere für das Kreatinin (Transportfehler 47,0%) und die Harnsäure (38,7%), weniger für das Gesamtcholesterin (22,9%), die Triglyceride (14,3%) und die Glucose (13,6%). Es ist deshalb nötig, Parameter mit hohen Transportfehler, wie z.B. das Kreatinin, so lange nicht in Programme aufzunehmen, die Postversand vorsehen, bis die Störungen im einzelnen analysiert und z.B. durch Verbesserung der Methodik [6] eliminiert sind. Die Übereinstimmung der Beantwortung eines Fragebogens mit gleichlautendem Interview wird als Vergleich bei denselben Probanden (n=235) herangezogen. Hier schwanken die Übereinstimmungen zwischen 98,7% und 61,7% je nach Frage. Die Beantwortung von Fragebogen liegt damit im Prinzip in der gleichen Größenordnung der Genauigkeit, wie Meßergebnisse von Laborwerten, sofern das Material am Postweg verschickt wird.
    Notes: Summary The exactitude of some widely used laboratory tests (triglycerids, cholesterol, glucose, uric acid, creatinine) is examined in a situation relevant for practising physicians. Different statistical methods for reporting errors are compared. Accuracy and precision are useful measures for the quality of analytic procedures. They are not sufficient for medical judgement for a single patient, since sampling procedures, type of sample or transport and storage of sample are not considered in accuracy and precision. Such sources of error can largely devaluate the quality of accuracy and precision and of the analytic procedures. Error coefficients are proposed as a new method of reporting laboratory errors. The mathematical model starts with an analysis of variance and total error, technical error and transport error are defined. The study shows that the error introduced by transporting serum via postal service compared to that conveyed in a cooled transport box by a special car is considerable. It is nearly impossible for a physican to use single laboratory value for a rational decision “normal—not normal” if the values are based on samples which are sent by postal service and if the values lie in the broad borderline between the normal and pathological area. This is especially true for creatinine (transport error 47.0%) and uric acid (transport error 38.7%), but not so much for cholesterol (22.9%), triglicerids (14.3%) and glucose (13.3%). Variables with high transport error like creatinine should not be used in screening programs, as long as the transport is made by postal service and the method is not improved. The agreements between the answers of a questionnaire and of an interview are analysed with the same patients (n=235). These agreements lie between 98.7% and 61.7% depending on the single question. The exactitude of medical questionnaires is in the same size order as the exactitude of laboratory tests—at least when the sample is sent by postal service.
    Type of Medium: Electronic Resource
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