Diagnostic and prognostic research in paediatrics: Children with meningeal signs
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- Augusta Bosmans
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1 Diagnostic and prognostic research in paediatrics: Children with meningeal signs Diagnostisch en prognostisch onderzoek in de kindergeneeskunde: Kinderen met meningeale prikkeling Proefschri.ft Ter verkrijging van de graad van doctor aan de Erasmus Universteit Rotterdam op gezag van de Rector Magnificus Prof.dr.ir. J. H. van Bemmel en volgens besluit van het College voor Promoties De openbare verdecliging zal plaatsvinden op woensdag 13 juni 2001 om uur door Rianne Oostenhrink geboren te Culemborg
2 Promotiecommissie Promotores: Overige leden: Copromotor: Prof-dr. D. E. Grobbee Prof.dr. H. A. Billier Prof.dr. R. de Groot Prof. dr. W. F. M. Arts Prof.dr. F. F. H. Rutten Dr. H.A. Moll The studies described in this thesis were supported by a grant from the Health Care Insurance Council of the Netherlands. The printing of this thesis was financially supported by the Julius Centre for Patient Oriented Research, Utrecht and Glaxo Wellcome B.V. Cover:Chopin's Waterloo, 1962 ArrnanArchives, APA reprinted with kind permission from the artist. Rianne Oostenbrink, 200 I. No part of this thesis may be reproduced or transmitted in any form, by any means, electronic or mechanical, without written permission from the copyright owner. ISBN
3 VoorArjan
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5 Contents 1 Introduction 1.1 Clinical presentation and diagnostic dilemmas in children with meningeal signs Outline of the thesis and aims of the study Diagnostic procedures in children with meningeal signs 2.1 Signs of meningeal irritation at the emergency department: How often bacterial meningitis? Prediction of bacterial meningitis in childhood: reduction of lumbar punctures Children with meningeal signs: when to start empirical antibiotic treatment? A diagnostic decision rule for management of children with meningeal signs Prognostic aspects of bacterial meningitis 3.1 Sequelae after bacterial meningitis Early prediction of neurological sequelae after bacterial meningitis The EQ-5D and the Health Utilities Index for permanent sequelae after meningitis - a head-to-head comparison Economic evaluation in paediatrics 4.1 Cost reduction by introduction of a diagnostic decision rule in children with meningeal signs Cost-utility analysis of patient care in children with meningeal signs Diagnostic research in clinical practice: prospects and problems Summary 6.1 Summaryandfutureperspectives Samenvatting List of co-authors Dankwoord Curriculum vitae
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7 Introduction
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10 Dankwoord
11 Dankwoord Onderzoek doen is een stukje teamwork en ik wil alle medespelers heel hartelijk bedanken v~~r hun inzet. De enthousiaste samenwerking met velen vanuit verschillende disciplines heb ik als een groot voorrecht ervaren. Dr. H. A. Moll, co-promotor, beste Henriette, met jou enthousiasme en optirnisme heb je me als student al warm gemaakt voor het doen van wetenschappelijk onderzoek. lk wil je heel hartelijk bedanken voor de stimulerende begeleiding in de afgelopen jaren, zodat zowel het onderzoek als de onderzoeker konden groeien. De promotoren Prof. Dr. D. E. Grobbee en Prof. Dr. H. A. Biiller dank ik v~~r hun begeleiding en constructieve ideeen. Beste Rick, je wist de vragen toch altijd vanuit hun oorsprong te verduidelijken, wanneer ik als onderzoeker te dicht op de resultaten zat. Bedankt veer je verhelderende visie! Prof. R. de Groot, Prof. Dr. W. F. M. Arts, Prof. Dr. F. F. H. Rutten, en Prof Dr. J. Lubsen, leden van de promotiecommissie, wil ik bedanken voor de beoordeling van dit proefschrift en voor hun bijdrage aan de definitieve versie. Beste Ronald, ook heel hartelijk bedankt voor de gezellige infectie-uitjes en congressen, die ik met de subafdeling infectie- en immuunziekten mocht delen! Dr. K. G. M. Moons, beste Carl, heel hartelijk bedankt voor de intensieve en gezellige begeleiding in de afgelopen jaren. Je hebt me geleerd dat onderzoek nooit af is, en dat de motivatie om verder te gaan daar ook uit voortkomt. Lang leve de electronische snelweg tussen Utrecht en Rotterdam voor de vele vraag-en antwoordmailtjes. Sacha Bleeker, Carola Bouwhuis, Monique Kromhout en Ezra Piepers, lieve kamergenoten, hartelijk bedankt voor de leuke tijd en steun bij onderzoeksperikelen. Sacha, bedankt voor je inbreng als onderzoeksmaatje binnen het project en natuurlijk dat je als paranimf naast me staat! Chantal Theunissen en Marielle Maas wil ik hartelijk bedanken voor hun bijdrage tijdens het onderzoek. Willy Atema, bedankt voor de gezelligheid, steun en betrokkenheid tijdens de projectjaren. Dr. G. Derksen-Lubsen, beste Arda, dank voor je inspirerende ideeen en je inzet om het project letterlijk en figuurlijk in een breder perspectief te plaatsen. Drs. I. Hiemstra, beste Idske, bedankt voor de prettige samenwerking. Mw Dr. M. L. Essink-Bot, beste Marie-Louise, je introduceerde me in de veelzijdigheid van kwaliteit van leven onderzoek. Bedankt voor de leuke samenwerking en hopelijk nog veel 'kinderqol' in de toekomst! Dr. W. K. Redekop en Drs. J. B. Oostenbrink, beste Ken en Jan, jullie plaatsten de medische zorg in een econoruisch perspectief. Bedankt v~~r de prettige samenwerking. Beste Jan, bedankt dat je je nichtje ter zijde staat als paranimf! Dr. A. R. T. Donders, beste Rogier, dank voor je hulp en creatieve adhoc oplossingen als het project om nieuwe statistische inzichten vroeg. Drs M. J. Twijnstra, beste Minke, hoe hadden al die statusgegevens zonder jou in een bruikbaar bestand moeten komen? Dank je voor het databeheer en inzet als er tech nog even iets tussendeor moest. 180
12 Da.nkT.voord Mede-onderzoekers in het Sophia, beste Dick, Edwin, Geert, Jan Erik, Jeroen, Laurens, Leon, Marcel, Paul, Pieter, Thee, Ward, Annernarie, Annernarie (F). Barbara, Clemenlien, Daphne, Debby, Ester, Hannerieke, Heslien, Hettie, Inge, Jessie, Jose, Karen, Maartje, Margriet, Marja, Nicolette, Saskia, Sophie, Venje, en Yvonne bedankt v~~r de gezellige WP-uurtjes, aio-weekenden en discussies over en tijdens het onderzoeksleven. Onderzoekers en epideroiologen van het Julius Centrum, beste Julianen, dank jullie v~~r de samenwerking en gezelligheid tijdens roijn 'Utrecht-dagen', het WEON en op de cursussen. De arts-assistenten en artsen van het Sophia en Juliana kinderziekenhuis en van de afdeling kindergeneeskunde van het Sint Franciscus Gasthuis en Reinier de Graaf Gasthuis wil ik hartelijk bedanken v~~r hun bijdrage in de prospectieve fase van het onderzoek. Lieve papa en mama, om iets zelf te doen moet je wei de nodige bagage meegekregen hebben. Bedankt v~~r jullie steun die altijd zo vanzelfsprekend lijkt. Tot slot, lieve Arre, dank je wei v~~r je support en aanwezigheid om altijd weer op terug te vallen. Zoals je weet is een twee-cilinder zo handig omdat eentje het altijd nog wei doet. En nu in volle vaart samen de toekomst tegemoet..! Bedankt! Rianne 181
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14 Curriculum vitae The author of this thesis was born on May 14th, 1972, in Culemborg, She attended the secondary school Scholengemeenschap Melanchthon in Rotterdam and passed the VWO exam in She started her medical training in 1990 at the Faculty of Medicine and Health Sciences of the Erasmus University, Rotterdam. During her study, she was a member of the Netherlands Medical Student Committee and the Dutch national student co-ordinator of the Erasmus student exchange program. As a student, she participated in a study on diagnostic procedures in children with a urinary tract infection, supervised by Dr. H. A. Moll at the outpatient department of the Sophia Children's Hospital, Rotterdam. During the internships, she stayed three months at the paediatric department of the Hospital Santo Antonio, Porto Alegre, Brasil. She obtained her medical degree in March From May till December 1997 she worked as a resident at the paediatric department of the Albert Schweitzer Hospital, Dordrecht. In December 1997 she started working as a research physician at the Ontwikkelingsgeneeskunde project 'Systematic diagnostic evaluation in paediatrics' as presented in this thesis, performed at the Sophia Children's Hospital, Rotterdam and the Julius Centre for General Practice and Patient Oriented Research, University Medical Centre, Utrecht, and supervised by Dr. H. A. Moll and Prof. Dr. D. E. Grobbee. She obtained her MSc in Clinical Epidemiology at the Netherlands Institute for Health Sciences, Erasmus University Rotterdam in June In February 2001 she started her training in paediatrics (first as agnio) at the Sophia Children's Hospital, Rotterdam (head Prof. Dr. H. A. Biiller). 183
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