Publicaties. Ziekenhuis s-hertogenbosch Onder redactie van: Wetenschapscommissie Wetenschapsbureau

publicaties Jeroen Bosch Ziekenhuis 2009-2010

Publicaties Jeroen Bosch Ziekenhuis 2009-2010

’s-Hertogenbosch 2011 Onder redactie van: Wetenschapscommissie Wetenschapsbureau

Wetenschap: de brug tussen onderzoek en praktijk Publicaties Jeroen Bosch Ziekenhuis 2010

Voorwoord Voor u ligt het publicatieboek 2010 van het Jeroen Bosch Ziekenhuis (JBZ). Hier staan alle wetenschappelijke publicaties van dat jaar in. Het overzicht laat zien dat wij behoren tot één van de topklinische ziekenhuizen van Nederland. Niet zonder reden, want we doen veel op dat gebied. Daarnaast leest u in deze uitgave diverse artikelen over managers, onderzoekscoördinatoren, artsen, verpleegkundigen en artsen in opleiding. Ja, we nemen u letterlijk mee naar de alledaagse praktijk van het onderzoeksveld. Het zijn persoonlijke verhalen waarin iedereen het belang van onderzoek vanuit een eigen invalshoek benadrukt. Zo komt u meer te weten over de vier verschillende onderzoekslijnen die binnen het JBZ bestaan: • Kanker, afweer en infectie; • Innovatie in techniek; • Hart en Vaten; • Leven in balans. U krijgt uitleg over wat deze onderzoekslijnen inhouden en wat de speerpunten en richtlijnen zijn. Daarnaast geven we u hopelijk een beter beeld van enkele onderzoeken die binnen het JBZ lopen. Ook ziet u in de artikelen terug hoe onderzoekers tegen wetenschap aankijken: wat vindt iemand nuttig? Waar haalt hij of zij voldoening uit? Maar ook: waar loopt diegene eventueel tegen aan? Laat deze boeiende verhalen voor u een stimulans zijn om in de toekomst onderzoek te blijven doen. Want wetenschap is enorm belangrijk om onze kwaliteit van zorg te verbeteren: het slaat de brug tussen onderzoek en de dagelijkse praktijk. Namens de wetenschapscommissie en het Wetenschapsbureau, Judie van den Elshout Staffunctionaris Wetenschapsbureau/ Cluster Leerhuis

voorwoord

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Inhoudsopgave

Voorwoord Interview: Willy Spaan en Marjolein Schouten Rob van Marum Esther de Vries Koop Bosscha Ellen Hoogeveen Linda Kampschreur Maaike Kusters Mirrian Hilbink

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6 8 10 12 14 57 64 132

1. ANESTHESIOLOGIE

17

2. CARDIOLOGIE

19

3. CHIRURGIE

21

4. DERMATOLOGIE

31

5. GERIATRIE

33

6. GYNAECOLOGIE

37

7. INTENSIVE CARE GENEESKUNDE

43

8. INTERNE GENEESKUNDE

47

9. KINDERGENEESKUNDE

59

10. KLINISCHE CHEMIE & HEMATOLOGIE

67

11. KLINISCHE FYSICA

73

12. KNO-HEELKUNDE

75

13. LONGZIEKTEN

77

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Publicaties 2009-2010 jeroen bosch ziekenhuis

14. MEDISCHE MICROBIOLOGIE

81

15. MOLECULAIRE DIAGNOSTIEK

89

16. NEUROLOGIE

95

17. NUCLEAIRE GENEESKUNDE

99

18.

OOGHEELKUNDE

101

19.

ORTHOPEDIE

103

20.

PATHOLOGIE

105

21.

PLASTISCHE CHIRURGIE

107

22. RADIOLOGIE

109

23. REUMATOLOGIE

115

24. REVALIDATIEGENEESKUNDE

117

25. SPOEDEISENDE GENEESKUNDE

119

26 UROLOGIE

121

27.

ZIEKENHUISFARMACIE

125

28

OVERIGE STAFDIENSTEN

127

29. DIVERSEN

129

Wetenschapsmiddag 2009 Wetenschapsmiddag 2010

130 131

1. De rol van mri onderzoek in het diagnostisch traject van de oudere alzheimer patiënt 1. 2. Nordic walking in parkinson’s disease: improves walking speed but leaves stride length unchanged 3. Evaluation of a diagnostic algorithm for acute q-fever in an outbreak setting 4. Vkorc1 - resistent voor de trombosedienst 5. Effecten van fast-track protocol na een cystectomie met urinedeviatie 6. Medicatiebewaking ‘next generation’ 7. Accuratesse van transrectale echografie in de preoperatieve stadiering van rectum lesies mogelijk geschikt voor transanale endoscopische microchirurgie (tem) 8. Acute q-fever-related mortality in the Netherlands(tem) 9. The value of an artificial neural network in the decision-making for prostate biopsies Bijlage I Wetenschappelijke publicaties 2009-2010 opgenomen in PubMed

inhoudsopgave

134 135 136 137 138 139

141 142 143

144

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Samen zetten we net dat stapje éxtra Binnen het Jeroen Bosch Ziekenhuis staan onderzoek en opleiding hoog in het vaandel. Daarom stimuleert het management artsen, verpleegkundigen en andere paramedici om hier tijd en energie in te steken. Willy Spaan en Marjolein Schouten vertellen over deze ambities. Prof. dr. Willy Spaan is voorzitter van de Raad van Bestuur van het Jeroen Bosch Ziekenhuis en hoogleraar in Leiden. Toen ik hier kwam werken, heb ik mij voorgenomen om wetenschap en met name het toegepast onderzoek prominent op de agenda te zetten. Want mijns inziens is onderzoek essentieel om de kwaliteit van zorg en de kwaliteit van het onderwijs te verbeteren.” Ook Marjolein Schouten, manager van de Jeroen Bosch Academie, zet zich in om onderzoek beter op de kaart te zetten. “Verpleegkundigen kijken niet altijd kritisch genoeg naar zorgverlening: waarom doen wij de dingen die wij doen? En waar kunnen we verbeteren? Dat vind ik jammer, want een kritische en nieuwsgierige houding is nodig om het JBZ het meest patiëntgerichte en -veilige ziekenhuis te laten zijn.” In de genen “Gelukkig is er inmiddels veel meer aandacht voor het doen van onderzoek”, aldus Spaan. “Ik merk dat medewerkers steeds ambitieuzer en kritischer worden. Ze hebben letterlijk de drive beter te willen zijn dan anderen. Ik vind het belangrijk dat deze onderzoekscultuur bij iedereen in de genen gaat zitten.” Schouten vult

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aan: “Ook binnen de vereniging van samenwerkende topklinische opleidingsziekenhuizen (stz) neemt de belangstelling voor onderzoek toe. Zo leren wij veel van de onderzoeksmethoden van het St. Antonius Ziekenhuis in Nieuwegein en het Catharina-ziekenhuis in Eindhoven.” Focussen Spaan vindt een aantal dingen belangrijk: “We moeten meer met academische ziekenhuizen samenwerken. Want we versterken elkaar op veel fronten, zoals het nadenken over de onderzoeksvraag, het bedenken van hele onderzoeksprogramma’s en het gebruik maken van elkaars onderzoeksfaciliteiten. Door deze samenwerking ontstaat er een vorm van wederkerigheid. Daarbij moet iemand een duidelijke koers varen. Want je kunt niet alles onderzoeken. Het gaat om focussen en de juiste richting bepalen.” Schouten benadrukt nog een belangrijk punt: “Het doen van onderzoek kost geld. Daarom zijn subsidies essentieel. Niet alleen voor wetenschappelijke analyses, maar juist ook voor toegepast of praktijkgebonden onderzoek. Onze onderzoekspopulaties zijn hier uitermate geschikt voor.” Elkaar inspireren Beiden hebben vertrouwen in de toekomst. Spaan: “De komende jaren gaan we het doen van onderzoek verder professionaliseren. Onderzoekstrajecten moeten meer structuur en vorm krijgen. Daarbij is het belangrijk fondsen te blijven werven om de nodige ondersteuning beter in te richten.” Schouten knikt instemmend en voegt daarbij: “We trainen medewerkers tot hooggekwalificeerde zorgprofessionals. Daarbij geven we iemand die competenties mee die nodig zijn voor het doen van onderzoek. Dit geldt voor artsen, verpleegkundigen of andere paramedici. Hierin werken we bijvoorbeeld samen met een academische werkplaats. Dit is een (kennis)infrastructuur waarin praktijk, onderzoek, beleid en opleiding met elkaar samenwerken.” Spaan concludeert stellig: “Al met al werken we aan een betere onderzoekscultuur. Een natuurlijke werkomgeving waar we elkaar inspireren en verder helpen. Samen zetten we net dat stapje éxtra!”

interview Willy Spaan en Marjolein Schouten

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Wie zaait, zal oogsten

Het Jeroen Bosch Ziekenhuis vindt opleiding en onderzoek belangrijk. Dat blijkt uit het feit dat niet alleen artsen, maar ook verpleegkundigen en assistenten hun vak steeds vaker vanuit wetenschap benaderen. Ook Rob van Marum ziet de toegevoegde waarde hiervan. Hij werkt er sinds ’n jaar als klinisch geriater en klinisch farmacoloog. Hij vertelt graag over zijn ervaringen. “Ik behandel oudere patiënten, die vaak meerdere aandoeningen tegelijkertijd hebben”, vertelt Van Marum. “Denk hierbij aan mobiliteit- en continentieproblemen, somberheid en tekortkomingen in het geheugen.” Opleidingsklimaat “Bovendien ben ik naast het werk als clinicus en opleider aangesteld als onderzoekscoördinator”, vervolgt Van Marum zijn verhaal. “Samen met nog drie anderen kregen we de opdracht op het wetenschappelijk onderzoek binnen het JBZ te verbeteren. Want het ziekenhuis wil tot de top van opleidingsziekenhuizen horen. Dat betekent concreet dat we samen met het wetenschapsbureau, -commissie en de Jeroen Bosch Academie een goed opleidingsklimaat willen neerzetten. Denk aan het beter faciliteren van onderzoek met het opstellen van procedures, statistische ondersteuning met dataverwerking en analyse. Dit om uiteindelijk tot meer wetenschappelijke publicaties te kunnen komen. Dat geeft ons een gezicht naar buiten.”

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Leven in Balans Elke onderzoekscoördinator heeft een eigen aandachtsgebied. Van Marum: “Ikzelf ben verantwoordelijk voor de onderzoekslijn Leven in Balans. Deze onderzoekslijn sluit goed aan bij de kernwaarden kwaliteit, innovatie en persoonlijke aandacht in het medische beleidsplan. Binnen het ziekenhuis verlenen we op alle terreinen patiëntenzorg met een chronisch of preventief karakter. De overkoepelende structuur van een onderzoekslijn zorgt ervoor dat de samenhang toeneemt. Voor deze lijn richt ik mij vooral op de domeinen preventie van kwetsbaarheid, waaronder (medicatie)veiligheid, bewegen en gezondheid en cognitie. Kortom, dit biedt de kans wetenschappelijk onderzoek op zowel somatisch als ondersteunend gebied in het Jeroen Bosch Ziekenhuis verder te ontwikkelen. Dat vind ik belangrijk!” Olievlek Van Marum ziet het als zijn taak het wetenschappelijk onderzoek als een olievlek binnen JBZ te verspreiden. “Ik probeer zoveel mogelijk arts-assistenten of verpleegkundigen enthousiast te maken voor het doen van onderzoek. Want ik vind dat we de aanwezige talenten binnen onze organisatie zoveel mogelijk moeten benutten. Om dit te bereiken, benader ik de connecties binnen mijn netwerk van academische ziekenhuizen en universiteiten. Ook zoek ik daarbij de samenwerking op met apothekers, psychiaters of fysiotherapeuten. Door deze verschillende partijen bij elkaar te brengen, bereiken we nog veel meer.” Op de goede weg Ondanks het feit dat Van Marum veel vertrouwen heeft in de toekomst, ziet hij toch ook een aandachtspunt. “Samen met de andere onderzoekscoördinatoren hebben we de ambitie het JBZ te positioneren als onderzoeksziekenhuis. We zijn al op de goede weg, maar hier en daar kan het nog beter. Want soms ontbreekt het aan besef dat er letterlijk tijd moet worden vrijgemaakt voor onderzoek. Dat is nog wel eens lastig. Want onze cultuur is er primair op gericht om patiëntenzorg te bieden. Hierdoor krijgt het doen van onderzoek geen prioriteit. Dat is funest als je wil dat iets vorm krijgt. Ik weet zeker dat als we hier vanaf nu bewust meer aandacht geven, zal dat ons vooruit helpen in de toekomst. Immers, wie zaait zal oogsten!”

interview Rob van marum

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Over muren heen kijken

Kinderarts dr. Esther de Vries werkt sinds 1997 in het Jeroen Bosch Ziekenhuis. Haar subspecialisme richt zich op infectieziekten en afwijkingen aan het afweersysteem. Dagelijks krijgt ze ouders en kinderen van verschillende leeftijden met diverse ziektebeelden in haar spreekkamer. Het doen en begeleiden van onderzoek boeit haar enorm. “Ik kwam hier werken om de kinderimmunologie en –infectiologie op te zetten”, steekt De Vries van wal. “Dit is een topklinisch ziekenhuis dat zich veel bezighoudt met onderzoek en opleiding. Hier kon ik onderzoek combineren met brede patiëntenzorg op hoog niveau. Het is de kunst uit een grote groep patiënten met vaak voorkomende infecties juist díe mensen te filteren waarbij sprake is van een relatief zeldzame onderliggende aandoening.” Maatschappelijk belang De Vries is ook voorzitter van de wetenschapscommissie en coördinator van de ziekenhuisbrede onderzoekslijn Kanker, afweer en infecties: “Deze onderzoekslijn raakt alle medische specialismen en heeft ook een duidelijk maatschappelijk belang. Elk jaar behandelen we hier ongeveer 2000 nieuwe patiënten met tumoren. Door de vergrijzing groeit het aantal ouderen enorm. Dat gaat gepaard met verminderde weerstand tegen infecties en

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toenemen van oncologische aandoeningen. Ook maakt de maatschappij zich steeds meer zorgen over grote uitbraken van infectieziekten. Op al deze gebieden lopen onderzoekstrajecten.” Grote impact Ze heeft een duidelijke missie. De Vries: “We proberen subsidies te krijgen voor het uitvoeren van goede onderzoeken. Want deze leiden vaak tot publicaties waar anderen weer van kunnen leren. In universitaire centra doet men vaak onderzoek naar zeldzame ziektes waar slechts weinig mensen aan lijden. Hier kunnen we met onze eigen brede patiëntenpopulatie onderzoek doen naar veelvoorkomende ziekten, die samen grote maatschappelijke impact hebben. Juist dat vind ik ontzettend waardevol.” Kennis delen “Er zijn in de loop der jaren meer onderzoeksfaciliteiten gekomen”, vervolgt De Vries. “Zoals goede interne begeleiding en software om gegevens te verwerken. Ook zijn er nu een Wetenschapsbureau en de Jeroen Bosch Academy die initiatieven voor onderzoek ondersteunen. Hierbij stimuleren we afdelingen om beter met elkaar samen te werken. Door kennis te delen, wordt onze patiëntenzorg alleen maar beter.” Over muren heen kijken Niet alleen intern, maar ook extern zoekt het ziekenhuis de samenwerking steeds meer op. “Zo is Fhealinc een uniek samenwerkingsverband tussen dit ziekenhuis, HAS Den Bosch, Avans Hogeschool, De ZLTO en de Gemeente ’s-Hertogenbosch”, vertelt De Vries. “We willen ondernemingen en kennisinstellingen ondersteunen bij het bedenken en uitwerken van innovatieve diensten op het snijvlak van voeding en gezondheid. Deze partners werken bijvoorbeeld samen in het project Expertisecentrum voor Voeding, Afweer en Allergie (EVAA). Dit project legt zich toe op het ontwikkelen van producten en diensten op het gebied van voeding, afweer en allergie, op het fundament van de Zorgpaden Immunologie en Allergologie. Door deze samenwerkingsverbanden neemt onze kennis toe. Maar ook het bedrijfsleven plukt daar de vruchten van. Mijns inziens kunnen we nog veel meer over onze eigen muren heen kijken!” Meer informatie Heeft u vragen over dit onderwerp? Neem dan contact op met dr. Esther de Vries via tel. (073) 6992965 of e-mail [email protected]

interview esther de vries

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‘Successen moet je vieren’

Chirurg Koop Bosscha vindt dat het doen van onderzoek bijdraagt aan de kwaliteit van de patiëntenzorg. Het biedt immers de mogelijkheid om datgene wat je doet te evalueren, te checken en al dan niet bij te sturen. Daarom zet hij zich binnen het Jeroen Bosch Ziekenhuis al jaren in om dit te stimuleren. En met succes. Binnen het ziekenhuis is hij verantwoordelijk voor de onderzoekslijn Innovatie en Techniek. Bosscha licht toe: “Deze onderzoekslijn sluit goed aan bij de speerpunten oncologie en minimale invasieve chirurgie. We richten ons vooral op nieuwe onderzoeks- en behandelingsmethodieken van kanker. Verschillende vakgroepen zijn erg actief op dit gebied. Dit leidde al regelmatig tot media-aandacht. Ook vanuit maatschappelijk oogpunt is er veel belangstelling voor.” En niet zonder reden, aldus Bosscha: “Het levert een grotere patiëntgerichtheid op en mogelijkheden tot kostenbesparing. De resultaten van de onderzoeken, die binnen deze onderzoekslijn plaatsvinden, zijn goed. Dat helpt ons de topzorg te bieden, waar het Jeroen Bosch Ziekenhuis voor staat.”

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Onderzoek en opleiding Bosscha vertelt meer over de achtergronden. “Ik heb me de afgelopen jaren ingezet om onderzoek te stimuleren. Arts-assistenten willen daarom graag in ’s-Hertogenbosch werken omdat ze hopen op die manier een opleidingsplaats te krijgen. Op de goede weg “Dus we zijn al op de goede weg”, zegt Bosscha. “Zo houd ik me bijvoorbeeld bezig met een studie die analyseert waarom bij 20-30% van de patiënten dikke darmkanker – na een succesvolle operatie – tóch weer terugkomt. Daar wilden we een verklaring voor vinden. Dat is gelukt, want met nieuwe onderzoekstechnieken zien we uitzaaiingen beter, waardoor patiënten mogelijk beter te behandelen zijn. Randvoorwaarden Toch zijn er volgens Bosscha ook enkele aandachtspunten in het Bossche onderzoeksklimaat: “Om gedegen onderzoek te doen, zijn goede randvoorwaarden nodig, zoals: voldoende tijd en geld. Dat is helaas niet altijd beschikbaar. Daarom moeten we proberen mensen te faciliteren. Laten we hen structureel meer tijd geven om onderzoek te doen. Ook is het nuttig beter naar beschikbare subsidies te kijken. Dat maakt het gemakkelijker om een bepaald onderzoek op te starten. We moeten niet vergeten dat wij een van de grootste ziekenhuizen zijn van Nederland. Daar hoort een bepaalde deskundigheid, expertise en uitstraling bij.” Win-win situatie De toegevoegde waarde van het doen van onderzoek staat Bosscha duidelijk voor ogen: “Mijns inziens zou elke arts onderzoek moeten doen. Want het verrijkt je als mens en helpt het medische beroep en het Jeroen Bosch Ziekenhuis nog beter neer te zetten. Als we zo’n onderzoek vervolgens ook nog publiceren in een vooraanstaand wetenschappelijk vakblad, heeft de buitenwereld er ook nog profijt van. We hebben de patiënten en goede doktors in huis. Dat moeten we laten zien. Want daarmee zetten we dit ziekenhuis op de kaart. En zeg nou zelf: successen moet je vieren!”

interview koop bosscha

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“Onderzoek geeft ons richting voor de toekomst”

Dr. Ellen Hoogeveen is internist-nefroloog en epidemioloog binnen het Jeroen Bosch Ziekenhuis. Ze behandelt patiënten met een verminderde nierfunctie wat varieert van een licht verminderde nierfunctie tot nierfalen. Als wetenschappelijk onderzoekscoördinator is ze verantwoordelijk voor de onderzoekslijn Hart- en Vaatziekten. Wat haar visie is op deze onderzoekslijn? Dat licht ze graag even toe. “Deze onderzoekslijn sluit goed aan bij een van de speerpunten van dit ziekenhuis: cardiovasculaire geneeskunde”, trapt Hoogeveen af. “Een aanzienlijk deel van onze patiëntenpopulatie lijdt aan hart- en vaatziekten. Dit is een van de belangrijkste doodsoorzaken onder de algemene bevolking in Nederland. Ook neemt dit probleem verder toe door de vergrijzing. Ik waardeer dat dit topklinische ziekenhuis ook oog heeft voor dit onderwerp.”

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Uitdaging “Ik vind het leuk en inspirerend om onderzoekstrajecten op te zetten en jonge onderzoekers te stimuleren”, vervolgt Hoogeveen enthousiast. “Het is een uitdaging om analyses zo te presenteren dat wij de vertaalslag kunnen maken naar de praktijk. Zelf ben ik specifiek geïnteresseerd in het effect van overgewicht op de nierfunctie.” Obesitas neemt zowel wereldwijd als in Nederland epidemische vormen aan. Uit haar eigen onderzoek bij 1800 patiënten blijkt dat patiënten met ernstig overgewicht na niertransplantatie eerder hun niertransplantaat verliezen. Ook hebben zij een lagere levensverwachting dan patiënten met een normaal gewicht.” Subsidie Hoogeveen haalde nog meer resultaten uit haar onderzoek onder 2000 dialyse patiënten. “Iemand die obesitas heeft en jonger is dan 65 jaar heeft 70% meer kans om binnen zeven jaar te sterven dan patiënten met een normaal gewicht. Op dit moment onderzoeken we bij 500 pre-dialyse patiënten wat het effect is van obesitas op de nierfunctie en sterfte”. Onlangs heeft de Nierstichting subsidie aan Hoogeveen toegekend om het effect van visolie te onderzoeken op preventie van nierfunctieachteruitgang bij ruim 3000 patiënten na een recent hartinfarct. Dit onderzoek vindt plaats in nauwe samenwerking met prof. Dr. Ron Kusters, klinische chemicus. Door deze studie wordt een nieuwe chemische bepaling in ons ziekenhuis geïntroduceerd om de nierfunctie te meten: Cystatine-C.” Q-koorts en hart- en vaatziekten De recente Q-koorts epidemie in Noord-Brabant was aanleiding voor diverse onderzoeken naar de effecten en behandeling van chronische Q-koorts bij patiënten met hartklepafwijkingen en vaataandoeningen. Het onderzoek wordt gesubsidieerd door ZonMW, een organisatie voor gezondheidsonderzoek en zorginnovatie. Hierbij werkt men goed samen met diverse afdelingen van het JBZ: medisch microbiologie, chirurgie, cardiologie en interne geneeskunde. Op dit moment zijn twee promovendi bij dit onderzoek betrokken.” Kruisbestuiving Tot slot heeft Hoogeveen nog ideeën om het Bossche onderzoeksklimaat te verbeteren: “Om gedegen onderzoek te doen, zijn goede faciliteiten en randvoorwaarden voor succes nodig.” Ook is Hoogeveen voorstander van het delen van kennis. “Onderzoekers weten nog te weinig van elkaar waar ze mee bezig zijn. Het zou kunnen helpen om een overzicht op intranet te plaatsen waar alle wetenschappelijke onderzoeken van het JBZ opstaan met daarbij de contactpersoon. Door kennis te delen, ontstaat vaak kruisbestuiving en zetten we sneller een stap vooruit. Dat geeft ons richting voor de toekomst.”

interview ellen hoogeveen

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ANESTHESIOLOGIE Abstracts, voordrachten en posters Lechner TJ. Het epidurale blok: niet voelen, maar horen. DARA congres, Heeze, 2009.

Lechner TJ. H2B. APAD JBZ, juni 2010.

Lechner TJ. The Acoustic puncture assist Device. ESRA wintersymposium, Grindelwald Zwitserland, 2010.

Lechner TJ. Workshop APAD. OK dagen, jaarbeurs Utrecht, 2010.

Lechner TJ. Een nieuw geluid op de operatiekamer. Refereeravond UMC Gent, Belgie, 2009.

Van Niekerk J. Voordracht: corpus alienum in de trachea bij kinderen, een tricky gebeuren. Nederlandse OK dagen, Oktober 2009.

Lechner TJ, van Wijk MG. De akoestisch geleide ruggenprik. IGZ Utrecht, 2009.

Publicaties (niet pubmed) Iff I, Mosing M, Lechner T, Moens Y. The use of an acoustic device to identify the extradural space in standing horses. Vet Anaesth Analg. 2010 Jan;37(1):57-62. (Onderzoek verricht in Wenen.)

Anesthesiologie

Van Niekerk J, Cornelissen P. Aspiratie van een corpus alienum bij kinderen? Starre bronchoscopie bij spontane ademhaling. Nederlands Tijdschrift voor Anesthesiologie. 2010 Nov;5.

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CARDIOLOGIE Wetenschappelijke publicaties Esselink AC, de Ruijter AM, Daniëls MC. Application of NHG guidelines in patients referred for stable chest pain syndromes. Neth Heart J. 2010 Apr;18(4):178-82. PMID: 20428415 Trefwoorden: richtlijnen, angina pectoris

Wever PC, Arts CH, Groot CA, Lestrade PJ, Koning OH, Renders NH. Screening for chronic Q fever in symptomatic patients

with an aortic aneurysm or prosthesis. Ned Tijdschr Geneeskd. 2010;154(28):A2122. PMID: 20699030 Hassink RJ, Haerkens-Arends HE, Daniels MC. Extensive right coronary artery thrombosis. Neth Heart J. 2009 Mar;17(3):115-6. PMID: 19325905 Trefwoorden: hartinfarkt, coronairangiografie

Abstracts, voordrachten en posters Daniëls MC. Voordracht: coronaire syndromen in de praktijk, Venticare 2010, Utrecht, 2010. Daniëls MC. Voordracht: Hartfalen, Nationale Patiëntendagen 2010, RAI A’dam, 8-10-2010. Daniëls MC. Voordracht: Hartritmestoornissen, HAIO’s Universiteit Maastricht, 2010. Daniëls MC. Voordracht: Stabiele en Acute Coronaire

Cardiologie

Syndromen, HAIO’s Universiteit Maastricht, 2010. De Ruijter AM., Esselink AC., Daniëls MC. Referral for stable angina: how do primary care physicians adhere to guidelines? Posterpresentatie NVVC, Neth. Heart J.2009: 17, Suppl.1: 14 Liem SS., Renders NH., Bouter KP., Daniëls MC. Follow-up after diagnosis of Q-fever: the ’s-Hertogenbosch experience. Posterpresentatie NVVC, Neth. Heart J. 2010: 18, Suppl. 1:21 Trefwoorden: Q-koorts

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Daniëls MC. Organisatie WDH/JBZ symposium Hartfalen, Vught, 2009. Daniëls MC. Voordracht: ‘diagnostiek hartfalen’, huisartsen nascholing regio ’s-Hertogenbosch, 2009. Daniëls MC. Voordracht: Stabiele en Acute Coronaire Syndromen, HAIO’s Universiteit Maastricht, 2009. Daniëls MC. Voordracht: Hartritmestoornissen, HAIO’s Universiteit Maastricht, 2009. Daniëls MC. Voordracht: acute coronaire syndromen, NvHVV, 2009.

Publicaties (niet pubmed) Meijs MF, Meijburg HW, Elsman P, Daniëls MC. ST-segment elevation and ventricular tachycardia due to multivessel coronary artery spasm without significant coronary artery stenosis. Neth.J.Crit.Care 2009; 13:318-320. Trefwoorden: hartinfarkt, hartritmestoornis

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CHIRURGIE Wetenschappelijke publicaties Dassen AE, Lemmens VE, van de Poll-Franse LV, Creemers GJ, Brenninkmeijer SJ, Lips DJ, Vd Wurff AA, Bosscha K, Coebergh JW. Trends in incidence, treatment and survival of gastric adenocarcinoma between 1990 and 2007: a population-based study in the Netherlands. Eur J Cancer. 2010 Apr;46(6):1101-10. PMID: 20219351 Lips DJ, Koning OH. Coral reef syndrome: a thoracic aorta stenosis as explanation for a collection of symptoms. Ned Tijdschr Geneeskd. 2009 Jan 17;153(3):91-4. PMID: 19235346 Dassen AE, Lips DJ, Hoekstra CJ, Pruijt JF, Bosscha K. FDG-PET has no definite role in preoperative imaging in gastric cancer. Eur J Surg Oncol. 2009 May;35(5):449-55. PMID: 19147324 Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009 Jan;35(1):3-10. PMID: 18722078

Chirurgie

Koebrugge B, van Wensen RJ, Bosscha K, Dautzenberg PL, Koning OH. Delirium after Emergency/Elective Open and Endovascular Aortoiliac Surgery at a Surgical Ward with a High-standard Delirium Care Protocol. Vascular. 2010 Sep-Oct;18(5):279-87. PMID: 20822723 Koebrugge B, Bosscha K, Jager G, Ernst M. Accuracy of transrectal ultrasonography in staging rectal tumors that are clinically eligible for transanal endoscopic microsurgery. J Clin Ultrasound. 2010 Jun;38(5):250-3. PMID: 20186761 Koebrugge B, Bosscha K, Ernst MF. Transanal endoscopic microsurgery for local excision of rectal lesions: is there a learning curve? Dig Surg. 2009;26(5):372-7. PMID: 19923824 Koebrugge B, Koek HL, van Wensen RJ, Dautzenberg PL, Bosscha K. Delirium after abdominal surgery at a surgical ward with a high standard of delirium care: incidence, risk factors and outcomes. Dig Surg. 2009;26(1):63-8. PMID: 19169032

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Koebrugge B, Hermens RA. A women with a lumpy calf. Ned Tijdschr Geneeskd. 2010;154:A440. PMID: 20298633 Koebrugge B, van Leuken M, Ernst MF, van Munster I, Bosscha K. Percutaneous Cholecystostomy in Critically Ill Patients with a Cholecystitis: A Safe Option. Dig Surg. 2010 Oct 15;27(5):417-421. PMID: 20948216

in ’s-Hertogenbosch. Acta Chir Belg. 2009 Jan-Feb;109(1):42-6. PMID: 19341194 Van Vugt R, Bosscha K, van Munster IP, de Jager CP, Rutten MJ. Embolization as treatment of choice for bleeding peptic ulcers in high-risk patients. Dig Surg. 2009;26(1):37-42. PMID: 19155626

Wever PC, Arts CH, Groot CA, Lestrade PJ, Koning OH, Renders NH. Screening for chronic Q fever in symptomatic patients with an aortic aneurysm or prosthesis. Ned Tijdschr Geneeskd. 2010;154(28):A2122. PMID: 20699030

Van Luin M, Van der Ende ME, Richter C, Visser M, Faraj D, Van der Ven A, Gelinck L, Kroon F, Wit FW, Van Schaik RH, Kuks PF, Burger DM. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ ritonavir. AIDS. 2010 May 15;24(8):1223-6. PMID: 20299957

Koning OH, Kaptein BL, van der Vijver R, Dias NV, Malina M, Schalij MJ, Valstar ER, van Bockel JH. Fluoroscopic Roentgen stereophotogrammetric analysis (FRSA) to study three-dimensional stent graft dynamics. J Vasc Surg. 2009 Aug;50(2):407-12. PMID: 19631876

Faraj D, Ruurda JP, Olsman JG, van Geffen HJ. Five-year results of inguinal hernia treatment with the Prolene Hernia System in a regional training hospital. Hernia. 2010 Apr;14(2):155-8. PMID: 19898738

Van Vugt R, Kruse RR, Sterkenburg SM, Fritschy WM, Moll FL. (Semi-)Closed Endarterectomy in Occlusive Aortoiliac Disease. Ann Vasc Surg. 2010 May 13. PMID: 20471793 Van Vugt R, Kruse RR, Fritschy WM, Moll FL. Treatment of dilated venous bypass grafts with an expanded polytetrafluoroethylene-covered nitinol endoprosthesis. Vasc Endovascular Surg. 2009 Apr-May;43(2):190-2. PMID: 19074204 Van Vugt R, Bosscha K, Olsman J, Jager GJ, de Jager CP. Management of hepatic trauma: a 9-year experience

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Van der Sangen MJ, van de Wiel FM, Poortmans PM, Tjan-Heijnen VC, Nieuwenhuijzen GA, Roumen RM, Ernst MF, Tutein Nolthenius-Puylaert MC, Voogd AC. Are breast conservation and mastectomy equally effective in the treatment of young women with early breast cancer? Long-term results of a population-based cohort of 1,451 patients aged

Ruiterkamp J, Voogd AC, Bosscha K, Tjan-Heijnen VC, Ernst MF. Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature. Breast Cancer Res Treat. 2010 Feb;120(1):9-16. PMID: 20012891 Lammers EJ, Huibers P, van der Sangen MJ, van de Poll-Franse LV, Poortmans PM, Ernst MF, Lemaire BM, Meijs CM, Nuytinck HK, Voogd AC. Factors contributing to improved local control after mastectomy in patients with breast cancer aged 40 years or younger. Breast. 2010 Feb;19(1):44-9. Epub 2009 Nov 12. PMID: 19913419 Ruiterkamp J, Ernst MF, van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Voogd AC. Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol. 2009 Nov;35(11):1146-51. PMID: 19398188 Van den Broek FJ, de Graaf EJ, Dijkgraaf MG, Reitsma JB, Haringsma J, Timmer R, Weusten BL, Gerhards MF, Consten EC, Schwartz MP, Boom MJ, Derksen EJ, Bijnen AB, Davids PH, Hoff C, van Dullemen HM, Heine GD, van der Linde K, Jansen JM, Mallant-Hent RC, Breumelhof R, Geldof H, Hardwick JC, Doornebosch PG, Depla AC, Ernst MF, van Munster IP, de Hingh IH, Schoon EJ, Bemelman WA, Fockens P, Dekker E. Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TRENDstudy). BMC Surg. 2009 Mar 13;9:4. PMID: 19284647 Van la Parra RF, Ernst MF, Bevilacqua JL, Mol SJ, Van Zee KJ, Broekman JM, Bosscha K. Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer

Chirurgie

patients with a positive sentinel node biopsy: validation of the MSKCC breast nomogram. Ann Surg Oncol. 2009 May;16(5):1128-35. PMID: 19252954 Van Schaik PM, Hermans E, van der Linden JC, Pruijt JR, Ernst MF, Bosscha K. Micro-metastases in stages I and II colon cancer are a predictor of the development of distant metastases and worse disease-free survival. Eur J Surg Oncol. 2009 May;35(5):492-6. PMID: 18775627 Ritchie ED, Jager GJ, van der Linden JC, Bosscha K. Three adults with intra-abdominal lymphangioma. Ned Tijdschr Geneeskd. 2009 Mar 7;153(10):456-9. PMID: 19374097 Van Wensen RJA, Bosscha K, Jager GJ, van der Linden JC, Fijnheer R. An invasive process in the pancreas: sometimes lymphoma. [Een ruimteinnemend proces in het pancreas. Niet altijd een carcinoom.] Ned Tijdschr Geneeskd. 2009;153:B164. PMID: 19818177 Van Nes JG, Seynaeve C, Maartense E, Roumen RM, de Jong RS, Beex LV, Meershoek-Klein Kranenbarg WM, Putter H, Nortier JW, Van de Velde CJ; Cooperating investigators of the Dutch TEAM trial (including Bosscha K). Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Ann Oncol. 2010 May;21(5):974-82. PMID: 19875752 Brokelman WJ, Holmdahl L, Janssen IM, Falk P, Bergström M, Klinkenbijl JH, Reijnen MM. Decreased peritoneal tissue plasminogen activator during prolonged laparoscopic surgery. J Surg Res. 2009 Jan;151(1):89-93. PMID: 18541262

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Lensvelt MM, Brokelman WJ, Ivarsson ML, Falk P, Reijnen MM. Peritoneal transforming growth factor beta-1 expression during prolonged laparoscopic procedures. J Laparoendosc Adv Surg Tech A. 2010 JulAug;20(6):545-50. PMID: 20578923

Bakker OJ, van Santvoort HC, Besselink MG, van der Harst E, Hofker HS, Gooszen HG; Dutch Pancreatitis Study Group. Prevention, detection, and management of infected necrosis in severe acute pancreatitis. Curr Gastroenterol Rep. 2009 Apr;11(2):104-10. PMID: 19281697

Van Santvoort HC, Besselink MG, Bakker OJ, Vleggaar FP, Timmer R, Weusten BL, Gooszen HG; Dutch Pancreatitis Study Group. Endoscopic necrosectomy in necrotising pancreatitis: indication is the key. Gut. 2010 Nov;59(11):1587. PMID: 20732915

Cobben LP, Bakker OJ, Puylaert JB, Kingma LM, Blickman JG. Imaging of patients with clinically suspected appendicitis in the Netherlands: conclusions of a survey. Br J Radiol. 2009 Jun;82(978):482-5. PMID: 19098079

Bakker OJ, Go PM, Puylaert JB, Kazemier G, Heij HA; Werkgroep en klankbordgroep Guideline on diagnosis and treatment of acute appendicitis: imaging prior to appendectomy is recommended. Ned Tijdschr Geneeskd. 2010;154:A303. PMID: 20482926

de Vries EN, Prins HA, Crolla RM, den Outer AJ, van Andel G, van Helden SH, Schlack WS, van Putten MA, Gouma DJ, Dijkgraaf MG, Smorenburg SM, Boermeester MA; SURPASS Collaborative Group. Effect of a comprehensive surgical safety system on patient outcomes. N Engl J Med. 2010 Nov 11;363(20):1928-37. PMID: 21067384

Leeuwenburgh MM, Bakker OJ, Gorzeman MP, Bollen TL, Seldenrijk CA, Go PM. Fewer unnecessary appendectomies following ultrasonography and CT. Ned Tijdschr Geneeskd. 2010;154(17):A869. PMID: 20456809 Van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG; Dutch Pancreatitis Study Group. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010 Apr 22;362(16):1491-502. PMID: 20410514

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Swank HA, Vermeulen J, Lange JF, Mulder IM, van der Hoeven JA, Stassen LP, Crolla RM, Sosef MN, Nienhuijs SW, Bosker RJ, Boom MJ, Kruyt PM, Swank DJ, Steup WH, de Graaf EJ, Weidema WF, Pierik RE, Prins HA, Stockmann HB, Tollenaar RA, van Wagensveld BA, Coene PP, Slooter GD, Consten EC, van Duijn EB, Gerhards MF, Hoofwijk AG, Karsten TM, Neijenhuis PA, Blanken-Peeters CF, Cense HA, Mannaerts GH, Bruin SC, Eijsbouts QA, Wiezer MJ, Hazebroek EJ, van Geloven AA, Maring JK, D’Hoore AJ, Kartheuser A, Remue C, van Grevenstein HM, Konsten JL, van der Peet DL, Govaert MJ, Engel AF, Reitsma JB, Bemelman WA; Dutch Diverticular Disease (3D) Collaborative Study Group. The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann’s procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037).


BMC Surg. 2010 Oct 18;10:29. PMID: 20955571 van de Wall BJ, Draaisma WA, Consten EC, van der Graaf Y, Otten MH, de Wit GA, van Stel HF, Gerhards MF, Wiezer MJ, Cense HA, Stockmann HB, Leijtens JW, Zimmerman DD, Belgers E, van Wagensveld BA, Sonneveld ED, Prins HA, Coene PP, Karsten TM, Klaase JM, Statius Muller MG, Crolla RM, Broeders IA; Dutch Diverticular Disease (3D) Collaborative Study Group. DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial. BMC Surg. 2010 Aug 6;10:25. PMID: 20691040 Hermans E, van Schaik PM, Prins HA, Ernst MF, Dautzenberg PJ, Bosscha K. Outcome of colonic surgery in elderly patients with colon cancer. J Oncol. 2010;2010:865908. PMID: 20628482 Color II Study Group, Buunen M, Bonjer HJ, Hop WC, Haglind E, Kurlberg G, Rosenberg J, Lacy AM, Cuesta MA, D’Hoore A, Fürst A, Lange JF, Jess P, Bulut O,

Poornoroozy P, Jensen KJ, Christensen MM, Lundhus E, Ovesen H, Birch D, Iesalnieks I, Jäger C, Kreis M, van riet Y, van der Harst E, Gerhards MF, Bemelman WA, Hansson BM, Neijenhuis PA, Prins HA, Balague C, Targarona E, Luján Mompeán JA, Franco Osorio JD, Garcia Molina FJ, Skullman S, Läckberg Z, Kressner U, Matthiessen P, Kim SH, Poza AA. COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer. Dan Med Bull. 2009 May;56(2):89-91. PMID: 19486621 Richir MC, van Lambalgen AA, Teerlink T, Wisselink W, Bloemena E, Prins HA, de Vries TP, van Leeuwen PA. Low arginine/asymmetric dimethylarginine ratio deteriorates systemic hemodynamics and organ blood flow in a rat model. Crit Care Med. 2009 Jun;37(6):2010-7. PMID: 19384222 de Vries EN, Prins HA, Crolla RM, den Outer AJ, van Andel G, van Helden SH, Schlack WS, van Putten MA, Gouma DJ, Dijkgraaf MG, Smorenburg SM, Boermeester MA; SURPASS Collaborative Group. Effect of a comprehensive surgical safety system on patient outcomes. N Engl J Med. 2010 Nov 11;363(20):1928-37. PMID: 21067384

Boeken Van Doesburg IAJ, Besselink MGH, Bakker OJ, Van Santvoort HC, Gooszen HG, on behalf of the Dutch Pancreatitis Study Group. Antibiotics, Probiotics and Enteral Nutrition: Means to Prevent Infected Necrosis in AP. In: Tilg H, Mayerle J (eds): Clinical Update on Inflammatory Disorders of the Gastrointestinal Tract. Front Gastrointest Res. Basel, Karger, 2010, vol 26, pp 156–164

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Abstracts, voordrachten en posters Koebrugge B, Lips DJ, Pruijt JH, Van der Linden JC, Ernst MF, Bosscha K. Can we identify high-risk stage II colonic cancer patients? Najaarsvergadering NVGE/NVGIC, Veldhoven, 7 en 8 oktober 2010. Koebrugge B, Lips DJ, Putter H, Pruijt JH, Van der Linden CJ, Ernst MF, Bosscha K. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients - the EnRoute+study. ESSO 2010, Bordeaux, Frankrijk, 15-17 september 2010. Koebrugge B, Lips DJ, Pruijt JH, Van der Linden CJ, Ernst MF, Bosscha K. Adherence to national guidelines in stage II colinic cancer patients in the Netherlands. ESSO 2010, Bordeaux, Frankrijk, 15-17 september 2010. Koebrugge B, Lips DJ, Pruijt JH, Van der Linden JC, Ernst MF, Bosscha K. Can we identify high-risk stage II colonic cancer patients? ESSO 2010, Bordeaux, Frankrijk, 15-17 september 2010. Lips DJ, Koebrugge B, Liefers GJ, Putter H, Smit V, Van der Linden CJ, Pruijt JH, Van de Velde CJ, Bosscha K. The number of high risk factors in stage II (N0) colonic cancer patients is related to outcome. ESSO 2010, Bordeaux, Frankrijk, 15-17 september 2010. Ruiterkamp J, Ernst MF, De Munck L, Van der Heijden-Van der Loo M, Van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Voogd AC. Improved survival of patients with primary metastatic breast cancer in the period 1995-2007.

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ESSO 2010, Bordeaux, Frankrijk, 15-17 september 2010. Van la Parra RF, Peer PGM, Ernst MF, Bosscha K. Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN. ESSO 2010, Bordeaux, Frankrijk, 15-17september 2010. Ruiterkamp J, Voogd AC, Bosscha K, Tjan-Heijnen VC, Ernst MF. A systematic review of the impact of breast surgery on survival in patients with breast cancer and distant metastases at initial presentation. ESSO 2010, Bordeaux, Frankrijk, 15-17 september 2010. Van la Parra RF, Mulder D, Ernst MF, de Roos W, Bosscha K. Identification of lymphovascular invasion in breast biopsy specimens. ESSO 2010, Bordeaux, Frankrijk, 15-17september 2010. Van la Parra RF, Francissen C, Peer PG, Ernst MF, Mulder D, de Roos W, Bosscha K. Validation of the MSKCC nomogram to predict sentinel lymph node metastases in a Dutch breast cancer population. ESSO 2010, Bordeaux, Frankrijk, 15-17september 2010. Geertsema D, Dassen AE, Lips DJ, Hoekstra CJ, Nieuwenhuijzen GA, Bosscha K. Value of PET-CT in patients with gastric cancer. ESSO 2010, Bordeaux, Frankrijk, 15-17september 2010. Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Transanal endoscopic microsurgery for local excision of rectal lesions; is there a learning curve?


12th World Congress on Gastrointestinal Cancer, Barcelona, Spain, June 2010. Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Accuracy of transrectal ultrasonography (trus) in staging clinically suspected t1-lesions prior to transanal endoscopic microsurgery. 12th World Congress on Gastrointestinal Cancer, Barcelona, Spain, June 2010. Geertsema D, Dassen AE, Lips DJ, Hoekstra CJ, Nieuwenhuijzen GA, Bosscha K. Value of PET-CT in patients with gastric cancer. 12th World Congress on Gastrointestinal Cancer, Barcelona, Spain, June 2010. Geertsema D, Dassen AE, Lips DJ, Hoekstra CJ, Nieuwenhuijzen GA, Bosscha K. Value of PET-CT in patients with gastric cancer. Chirurgendagen 2010, Veldhoven, 21 mei 2010. Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Accuracy of Transrectal Ultrasonography in the preoperative staging of T1 rectal lesions suitable for Transanal Endoscopic Microsurgery. Chirurgendagen 2010, Veldhoven, 21 mei 2010 Koebrugge B. Transanal endoscopic microsurgery: staging and results. Voordracht regionale refereeravond regio Utrecht.’s Hertogenbosch, 1 juni 2010.

DCCG-dag, Amersfoort, 3 december 2010. Bosscha K, Lips DJ, Koebrugge B, Van der Linden JH, Nooijen P, Pruijt JH, Van de Velde CJ. Schildwachtklieronderzoek bij het coloncarcinoom, praktische implicaties voor chirurg en patholoog. DCCG-dag, Amersfoort, 3 december 2010. Van la Parra RF, Peer PGM, De Roos WK, Ernst MF, Bosscha K. Een eenvoudige risicoscore om de kans op nietschildwachtklier metastasen te schatten als de schildwachtklier positief is. Najaarsvergadering NVvH, Ede, 26 november 2010. Lemmens VEPP, Bosscha K, Van der Schelling G, Brenninkmeier S, Coebergh JWW, De Hingh IHJT. Significante verbetering van korte en lange termijnsresultaten na centralisatie van pancreaschirurgie in de IKZ-regio. Najaarsvergadering NVvH, Ede, 26 november 2010. Van la Parra RF, Francissen C, Peer PG, Ernst MF, Mulder D, de Roos W, Bosscha K. Validatie van het MSKCC nomogram om de kans op positieve schildwachtklieren te voorspellen. Chirurgendagen, Veldhoven, Mei 2010. Van la Parra RF, Mulder D, Ernst MF, de Roos W, Bosscha K. Identification of lymphovascular invasion in breast biopsy specimens. EBCC, Barcelona, maart 2010.

Voogd AC, Ruiterkamp J, De Munck L, Van der Heijden-Van der Loo M, Van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Ernst MF. Ontwikkelingen in de overleving van patiënten met primair gemetastaseerd mammacarcinoom in de periode van 1995 – 2007 en het effect van chirurgie. Chirurgendagen 2010, Veldhoven 21 mei 2010.

Van la Parra RF, Francissen C, Peer PG, Ernst MF, Mulder D, de Roos W, Bosscha K. Validation of the MSKCC nomogram to predict sentinel lymph node metastases in a Dutch breast cancer population. EBCC, Barcelona, maart 2010.

Bosscha K, Lips DJ, Koebrugge B, Van der Linden JH, Nooijen P, Pruijt JH, Van de Velde CJ. De En Route-studie.

Van la Parra RF, Barneveld PC, Ernst MF, Bosscha K. Disconcordance between number of scintigraphic and

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peroperatively identified sentinel lymph nodes and axillary tumour recurrence. EBCC, Barcelona, maart 2010. Van la Parra RF, Peer PG, Ernst MF, Bosscha K. Meta-analysis of predictive factors for non sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node. EBCC, Barcelona, maart 2010. Ruiterkamp J, Voogd AC, Tjan-Heijnen VC, Bosscha K, Ernst MF. A systematic review of the impact of breast surgery on survival of patients with distant metastases at initial presentation. EBCC, Barcelona, maart 2010. Van la Parra RF, Peer PG, Ernst MF, Bosscha K. Meta-analysis of predictive factors for non-sentinel lymph node metastases after a positive sentinel lymph node in breast cancer. SSO, St Louis, maart 2010. Koebrugge B, Koek HL, Van Wensen R, Dautzenberg PL, Bosscha K. Delirium na abdominale chirurgie op een chirurgische afdeling met geprotocolleerde aandacht voor het delirium. Najaarsvergadering NVvH Ede, 27 november 2009. Koebrugge B, Van Leuken M, Ernst MF, Van Munster I, Bosscha K. Percutane galblaasdrainage bij patiënten met een acute cholecystitis in slechte klinische toestand: een goede optie ?! Najaarsvergadering NVvH, Ede, 27 november 2009. Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Accuratesse van Transrectale Echografie in de preoperatieve stadiering van rectum lesies geschikt voor transanale endoscopische microchirurgie. Najaarsvergadering NVvH, Ede, 27 november 2009.

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Ruiterkamp J, Voogd AC, Tjan-Heijnen VC, Bosscha K, Ernst MF. Improved survival in patients with primary metastatic breast cancer treated with resection of the breast tumor. 34th ECCO/ESMO Multidisciplinary Congress, Berlin, Germany, 20-24 september 2009 (persconferentie ECCO/ESMO betreffende bovenstaande presentatie zie: http://www.ecancermedicalscience.com/tv/?play=240)

Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Transanal Endoscopic Microssurgery (TEM) in Tubulovillous Adenoma and T1 rectal lesions. 34th ECCO/ESMO Multidisciplinary Congress, Berlin, Germany, 20-24 september 2009. Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Accuracy of Transrectal Ultrasonography in the preoperative staging of rectal lesions suitable for Transanal Endoscopic Microsurgery. 34th ECCO/ESMO Multidisciplinary Congress, Berlin, Germany, 20-24 september 2009. Dassen AE, Lips DJ, Hoekstra CJ, Ernst MF, Bosscha K. Value of 18F-FDG PET-CT in staging gastric cancer. 34th ECCO/ESMO Multidisciplinary Congress, Berlin, Germany, 20-24 september 2009. Van la Parra RF, Ernst MF, Bosscha K. Schildwachtklierbiopsie na eerdere ipsilaterale mamma chirurgie. Bossche Mamma Congres, ’s Hertogenbosch, juni 2009. Looij BG, Kreb DL, van der Linden JC, Ernst MF, Pruijt JF, Bosscha K, Jager GJ, Rutten MJ. In vivo radio frequency ablation (RFA) in small breast cancer: preliminairy results. ECR 2009, Wenen, 6 maart 2009. Koebrugge B, Bosscha K, Ernst MF. Transanal Endoscopic Microsurgery for local resection of rectal lesions: initial results in a university affiliated


teaching hospital. SSO, Phoenix, USA, 5-8 maart 2009. Koebrugge B, Bosscha K, Jager GJ, Ernst MF. Accuracy of TransRectal UltraSonography (TRUS) in preoperative staging of rectal lesions suitable for Transanal Endoscopic Microsurgery. SSO, Phoenix, USA, 5-8 maart 2009. Ruiterkamp J, Voogd AC, Smilde T, Bosscha K, Ernst MF. Surgical resection of the primary tumor is associated with improved survival in patients with metastatic breast cancer at diagnosis. SSO, Phoenix, USA, 5-8 maart 2009. Ruiterkamp J, Voogd AC, Smilde T, Bosscha K, Ernst MF. The prognostic significance of tumor surgery in patients with primary metastatic breast cancer. SSO, Phoenix, USA, 5-8 maart 2009. Van la Parra RF, Ernst MF, Bosscha K. Sentinel lymph node biopsy after previous breast surgery. SSO, Phoenix, USA, 5-8 maart 2009. Van Baal MC, Besselink MG, OJ Bakker, van Santvoort HC, Schaapherder AF, Nieuwenhuijs VB, Gooszen HG, van Ramshorst B, Boerma D, for the Dutch Pancreatitis Study Group. Systematic review on timing of cholecystectomy after mild biliary pancreatitis. European Pancreatic Club 2010,June 2010, Stockholm, Sweden. BU Wu, OJ Bakker, GI Papachristou, K Repas, MG Besselink, HC van Santvoort, V Muddana, VK Singh, DC Whitcomb, HG Gooszen, PA Banks. Prognostic Value of Blood Urea Nitrogen (BUN) in the early assessment of Acute Pancreatitis: An International Study. Digestive Diseases Week, May 2010, New Orleans. Distinguished session.

Chirurgie

Voermans RP, Bakker OJ, van Brunschot S, van Santvoort HC, Boermeester MA, Timmer R, Nieuwenhuijs VB, Bruno MJ, Gooszen HG and Fockens P for the Dutch Pancreatitis Study Group. Prospective evaluation of endoscopic and conservative treatment of persistent symptomatic sterile pancreatic necrosis. Nederlandse Vereniging voor Gastro-Enterologie, March 2010, Veldhoven, Nederland. HC van Santvoort, MG Besselink, OJ Bakker, HS Hofker, MA Boermeester, CH Dejong, H van Goor, AF Schaapherder, CH van Eijck, TL Bollen, B van Ramshorst, VB Nieuwenhuijs, R Timmer, JS Laméris, PM Kruyt, ER Manusama, E van der Harst, GP van der Schelling, T Karsten, EJ Hesselink, CJ van Laarhoven, C Rosman, K Bosscha, RJ de Wit, AP Houdijk, MS van Leeuwen, E Buskens, HG Gooszen, for the Dutch Pancreatitis Study Group. Minimally invasive step-up approach versus open necrosectomy in necrotizing pancreatitis: randomized controlled multicenter trial (PANTER). International Association of Pancreatology/ American Pancreatic Association/ Japanese Pancreatic Society, November 2009, Honolulu, Hawaii. Van Baal MC, van Santvoort HC, Bollen TL, OJ Bakker, Besselink MG, Gooszen HG, for the Dutch Pancreatitis Study Group. Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis. International Association of Pancreatology/ American Pancreatic Association/ Japanese Pancreatic Society, November 2009, Honolulu, Hawaii. HC van Santvoort, OJ Bakker, MG Besselink, TL Bollen, K Fischer, H Gooszen, J van Erpecum. Predictors of common bile duct stones during early endoscopic retrograde cholangiopancreaticography in acute biliary pancreatitis. European Pancreatic Club, July 2009, Szeged, Hungary.

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OJ Bakker, HC van Santvoort, JC Hagenaars, TL Bollen, MG Besselink, HG Gooszen, AFM Schaapherder. Timing of Cholecystectomy in 418 patients with mild and severe biliary pancreatitis: Dutch multicenter experience. European Pancreatic Club, July 2009, Szeged, Hungary.

Bakker OJ, van Santvoort HC, Hagenaars JC, Bollen TL, Besselink MG, Gooszen HG, Schaapherder AF. Timing of cholecystectomy in 418 patients with mild and severe biliary pancreatitis: Dutch multicenter experience. European Pancreatic Club (EPC), July 2009, Szeged, Hongary.

Bakker OJ, van Santvoort HC, Besselink MG, Fischer K, Bollen TL, Boermeester MA, Gooszen HG. Timing of enteral nutrition in patients with predicted severe acute pancreatitis: an early start is associated with a reduction in bacteremia. Digestive Disease Week (DDW), May 2009, Chicago, USA.

Nijmeijer RM, Zhernakova A, Bakker OJ, van Santvoort HC, Boermeester MA, Gooszen HG, Akkermans LM, Wijmenga C , van Erpecum KJ. Genetic Variants of Farnesoid X Receptor (FXR) Predispose to Mortality and Infectious Complications in Acute Pancreatitis. Digestive Disease Week (DDW), May 2009, Chicago, USA.

Publicaties (niet pubmed) Lips DJ, Liefers GJ, Smit VTHBM, van der Linden JC, Pruijt HF, van de Velde CJH, Bosscha K. Behandeling van stadium I-II coloncarcinoom moet en kan beter. Medisch Contact 2010. Online 10 March 2010. Lips DJ, Koning OHJ. Een thoracale aortastenose als oorzaak voor een verzameling aan symptomen. Gamma Professional;oktober 2009.

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DERMATOLOGIE Wetenschappelijke publicaties Erceg A, Greebe RJ, Bovenschen HJ, Seyger MM. A Comparative Study of Pulsed 532-nm Potassium Titanyl Phosphate Laser and Electrocoagulation in the Treatment of Spider Nevi. Dermatologic surgery 2010;36:630-635. PMID: 20384753 Trefwoorden: KTP laser, spider naevi. Kleinpenning MM, Langewouters AMG, Kerkhof PCM van de, Greebe RJ. Severe pyoderma gangraenosum unresponsive to etanercept and adalimumab.

J Dermatolog Treat. 2010 Aug 1. PMID: 20673157 Trefwoorden: Pyoderma gangraenosum, biologicals.

van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized Patient. PLoS Pathog. 2010 Jul 29; 6(7): e1001024. PMID: 20686659

Abstracts, voordrachten en posters Greebe RJ. Voordracht: Praktische aspecten van chemische peelings. Nederlands Genootschap van Cosmetische Artsen, Nieuwegein, 9 juni 2009. Janssens RW. Voordracht Huid en diabetes. Diabetes vereninging Den Bosch, 2 december 2009.

dermatologie

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Publicaties (niet pubmed) Hoogeveen E, Broekman J, Janssens RW. Induction of eruptive benign melanocytic nevi after kidney transplantation. Dermatologia Kliniczna 2009;11:29-30 de Bruin IJ, Janssens RW, Seyger MM. Mijn kind heeft bulten onder de voeten! Ned Tijdschr Dermatol Venereol 2009;19:23. Van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, et al. (2010) Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized Patient. PLoS Pathog 6(7): e1001024. doi:10.1371/journal. ppat.1001024.

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GERIATRIE Wetenschappelijke publicaties Knol W, Keijsers CJPW, Jansen PAF, van Marum RJ. Systematic evaluation of rating scales for drug induced parkinsonism. J Clin Psychopharmacol. 2010; 30(1): 57-61 PMID: 20075649 Meulendijks D, Manesse CK, Jansen PAF, van Marum RJ, Egberts ACG. Antipsychotic-induced hyponatriemia: a systematic review of published evidence. Drug Safety. 2010; 33(2): 101-14. PMID: 20082537 Mannesse CK, van Puijenbroek EP, Jansen PA, van Marum RJ, Souverein PC, Egberts TC. Hyponatremia as an adverse drug reaction of antipsychotic drugs: a case-control study in VigiBase. Drug Safety. 2010; 33(7): 569-78. PMID: 20553058 van der Linden CMJ, Jansen PAF, van Marum RJ, Grouls RJE, Egberts ACG, Korsten HHM. Reasons for discontinuation of medication during hospitalization and documentation thereof: a descriptive study of 400 geriatric and internal medicine patients. Arch Int Med. 2010 Jun 28;170(12):1085-7. PMID: 20585080

geriatrie

van der Linden CM, Jansen PA, van Marum RJ, Grouls RJ, Korsten EH, Egberts AC. Recurrence of adverse drug reactions following inappropriate re-prescription: better documentation, availability of information and monitoring are needed. Drug Saf. 2010 Jul 1;33(7):535-8. PMID: 20553055 Kröger E, van Marum RJ, Souverein P, Egberts TC. Discontinuation of cholinesterase inhibitor treatment and determinants thereof in the Netherlands: A retrospective cohort study. Drugs Aging. 2010 Aug 1;27(8):663-75. PMID: 20658794 Kleijer BC, Heerdink R, Egberts ACG, Jansen PAF, van Marum RJ. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients. J Clin Psychopharmacol. 2010; Oct;30(5):526-30. PMID: 20814323 Spee J, van Marum RJ, Egberts ACG, Drenth van Maanen AC, Jansen PAF. The process of bringing medication in line: the additional benefits of a Structured Medication History. [Het Medicatie Afstemmingsproces op een afdeling geriatrie: de aanvullende waarde van een

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Gestructureerde Medicatie Anamnese.] Ned Tijdschr v Geneesk. 2010; 154: A904 PMID: 20356426 Koebrugge B, van Wensen RJ, Bosscha K, Dautzenberg PL, Koning OH. Delirium after Emergency/Elective Open and Endovascular Aortoiliac Surgery at a Surgical Ward with a High-standard Delirium Care Protocol. Vascular. 2010 Sep-Oct;18(5):279-87. PMID: 20822723 Wouters CJ, Dautzenberg L, Thissen A, Dautzenberg PL. Oral galantamine versus rivastigmine transdermal patch: a descriptive study at a memory clinic in The Netherlands. Tijdschr Gerontol Geriatr. 2010 Jun;41(3):146-50. PMID: 20593742 Sleegers MJ, Beutler JJ, Hardon WJ, Berden JH, Verhave JC, Conemans JM, Hollander DA, Dautzenberg PL, Hoogeveen EK. Reversible rapidly progressive dementia with parkinsonism induced by valproate in a patient with systemic lupus erythematosus. J Am Geriatr Soc. 2010 Apr;58(4):799-801. PMID: 20398172 Feitsma MT, van Laar T, Dautzenberg PL. The possible value of diagnosing MCI-DLB and treatment options. Tijdschr Gerontol Geriatr. 2009 Sep;40(4):168-72. PMID: 20088343 Dautzenberg PL, van der Zande JA, Conemans JM, Rikkert MG. Off-label drug use on a Dutch geriatric ward. Int J Geriatr Psychiatry. 2009 Oct;24(10):1173-4. PMID: 19771542 Nijboer H, Dautzenberg PL. Progressive supranucleair palsy: acetylcholineeseraseinhibitor a possible therapy?

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Tijdschr Gerontol Geriatr. 2009 Jun;40(3):133-7. PMID: 19731749 Robben SH, Sleegers MJ, Dautzenberg PL, van Bergen FS, ter Bruggen JP, Rikkert MG. Pilot study of a three-step diagnostic pathway for young and old patients with Parkinson’s disease dementia: screen, test and then diagnose. Int J Geriatr Psychiatry. 2010 Mar;25(3):258-65. PMID: 19582760 Robben SH, Sleegers MJ, Dautzenberg PL, Bergen FS van, Terbruggen JP, Rikkert MG. Pilot study of a three-step diagnostic pathway for young and old patients with Parkinson’s disease dementia: screen, test and then diagnose. Int J Geriatr Psychiatry. 2010 Mar;25(3):258-65 PMID: 19582760 Dautzenberg PL, Nijboer H, Wouters CJ. A triage system for non-urgent ambulant frail elderly. Tijdschr Gerontol Geriatr. 2009 Feb;40(1):24-8. PMID: 19326699 Koebrugge B, Koek HL, van Wensen RJ, Dautzenberg PL, Bosscha K. Delirium after abdominal surgery at a surgical ward with a high standard of delirium care: incidence, risk factors and outcomes. Dig Surg. 2009;26(1):63-8. PMID: 19169032 Hermans E, van Schaik PM, Prins HA, Ernst MF, Dautzenberg PJ, Bosscha K. Outcome of colonic surgery in elderly patients with colon cancer. J Oncol. 2010; 2010:865908. PMID: 20628482 Keijsers CJ, Custers EJ, ten Cate OT. A new, problem oriented medicine curriculum in Utrecht: less basic science knowledge. Ned Tijdschr Geneeskd. 2009;153:B400. PMID: 19785897


Abstracts, voordrachten en posters van Marum RJ Lezing: “Farmacokinetiek en –dynamiek bij ouderen” Cursus farmacologie voor verpleeghuisartsen. Nascholingsinstituut Gerion, VUMC, 9 april 2010.

van Marum RJ Lezing “Farmacokinetiek en polyfarmacie bij ouderen” Cursusdag landelijke ziekenhuisapothekers in opleiding. Utrecht. 17 nov 2010.

van Marum RJ Lezing: De oudere patient met onrust. Boerhave nascholing: Diagnostische strategieën. LUMC Leiden. 22 april 2010.

Kröger E, van Marum RJ, Souverein P, Carmichael PH, Egberts T. Treatment with Cholinesterase Inhibitors May Increase the Risk of Urinary Incontinence. 26th International Conference on Pharmacoepidemiology & Therapeutic Risk Management. Hilton Brighton Metropole Brighton, United Kingdom. August 19-22, 2010

van Marum RJ Lezing Drug management & polyfarmacy. Uitwisseling ouderengeneeskundigen UK en NL. Univ Maastricht. 19 mei 2010. van Marum RJ Lezing “CVA, medicatie en valkuilen” Symposium Got to Move; bewegen en multimorbiditeit na een beroerte”. Revalidatiecentrum trappenburg Huizen. 4 juni 2010. van Marum RJ Lezing “Samenwerking Health & Pharma”. Congres Dynamisch Noordoost. Den Bosch. 6 okt. 2010. van Marum RJ Lezing “Polypharmacie; bezwaren en bijwerkingen van medicatie bij kwetsbare ouderen” Congres Palliatieve zorg aan de dementerende patiënt. Amersfoort. 8 okt 2010. van Marum RJ Lezing “Medicamenteuze behandelingen voor dementie in de (nabije) toekomst: Hoop of wanhoop.” Landelijke 9e geheugenpolidag. Ede. 14 okt 2010. van Marum RJ Workshop “Psychofarmaca bij dementie” Landelijke 9e geheugenpolidag. Ede. 14 okt 2010.

geriatrie

Mannesse CK, Jansen PA, van Marum RJ, Sival RC, Kok, Haffmans PM, Egberts TC. Hyponatremia in elderly patients treated with antidepressant drugs: a cross-sectional study on prevalence and clinical characteristics. Poster EUGMS Dublin 2010. Van der Linden C, Jansen P, van Marum RJ, Grouls R, Egberts T, Korsten E. Improvement Of Pharmacovigilance At The Individual Patient Level; An Electronic System To Document Reasons For Medication Discontinuation And To Alert In Case Of Unwanted Represcription. Poster EUGMS Dublin 2010. Van den Heuvel PM, Los M, van Marum RJ, Jansen PA. Reasons of underprescribing in the elderly using polypharmacy: balanced prescribing by general practitioners. Poster Geriatriedagen 2010; 11-12 feb Drenth-van Maanen AC, van Marum RJ, Egberts AC, Spee J, Jansen PA. Het medicatie afstemmingsproces op een afdeling geriatrie: de aanvullende waarde van een gestructureerde medicatie anamnese. Poster Geriatriedagen 2010; 11-12 feb

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Publicaties (niet pubmed) Dautzenberg PL. Dementie ontmaskert. De POH 2009;2 (vol 5):8-10. Dautzenberg PL. Antidementiemiddelen: hun huidige en toekomstige therapeutische waarde. In Bijblijven Tijdschrift Praktische Huisartsengeneeskunde 2009-8:blz 40-9. Thissen AJ, Bergen van F, Jonghe de JF, Kessels RP, Dautzenberg PL. Bruikbaarheid en validiteit van de Nederlandse versie van de Montreal Cognitive Assesment (MoCA-D) bij het diagnosticeren van Mild Cognitive Impairment. TGG 2010;41:231-40.

Van Marum RJ Antipsychotic drug use and the risk of developing pneumonia. Aging Health 2010; 6(5): 529-532. Kleijer BC, van Marum RJ, Egberts ACG, Jansen PAF, Knol W, Heerdink ER. Risico op CVA bij ouderen die antipsychotica gebruiken. Psyfar. 2010; 4: 20-24. Kleijer BC, van Marum RJ, Egberts ACG, Jansen PAF, Frijters DHM, Heerdink ER, Ribbe MW. Het beloop van gedragsproblemen bij oudere verpleeghuispatiënten met dementie die worden behandeld met antipsychotica. Tijdschrift voor Ouderengeneeskunde 2010; 35 (2): 70-79. Van Marum RJ. Huidige en toekomstige therapieen voor de ziekte van Alzheimer. Tijdschrift voor Ouderengeneeskunde 2010; 35 (5): 172-9.

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GYNAECOLOGIE Wetenschappelijke publicaties Consten D, de Bruin JP, Bots RS, Hamilton CJ, Peeters MF. In vitro maturation of human egg cells. Introduction of a new artificial reproduction technique in the Netherlands. Ned Tijdschr Geneeskd. 2009 Jan 17;153(3):82-6. PMID: 19235344 Brandes M, van der Steen JO, Bokdam SB, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. When and why do subfertile couples discontinue their fertility care? A longitudinal cohort study in a secondary care subfertility population. Hum Reprod. 2009 Dec;24(12):3127-35. Epub 2009 Sep 26. PMID: 19783833 Brandes M, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. The relative contribution of IVF to the total ongoing pregnancy rate in a subfertile cohort. Hum Reprod. 2010 Jan;25(1):118-26. Epub 2009 Oct 24. PMID: 19855108 Brandes M, Hamilton CJ, Bergevoet KA, de Bruin JP, Nelen WL, Kremer JA.

gynaecologie

Origin of multiple pregnancies in a subfertile population. Acta Obstet Gynecol Scand. 2010 Sep;89(9):1149-54. PMID: 20804340 Penninx J, Brandes M, de Bruin JP, Schneeberger PM, Hamilton CJ. Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests. Eur J Obstet Gynecol Reprod Biol. 2009 Dec;147(2):178-82. Epub 2009 Sep 5. PMID: 19733956 Bensdorp AJ, Slappendel E, Koks C, Oosterhuis J, Hoek A, Hompes P, Broekmans F, Verhoeve H, de Bruin JP, van Weert JM, Traas M, Maas J, Beckers N, Repping S, Mol BW, van der Veen F, van Wely M. The INeS study: prevention of multiple pregnancies: a randomised controlled trial comparing IUI COH versus IVF e SET versus MNC IVF in couples with unexplained or mild male subfertility. BMC Womens Health. 2009 Dec 18;9:35. PMID: 20021654 De Reu PA, van Diem MT, Eskes M, Oosterbaan HP, Smits LJ, Merkus JM, Nijhuis JG. The Dutch Perinatal Audit Project: a feasibility study for nationwide perinatal audit in the Netherlands.

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Acta Obstet Gynec Scand. 2009;88(11):1201-8. PMID: 19900138

De Reu PA, Oosterbaan HP, Smits LJ, Nijhuis JG. Avoidable mortality in small-for-gestational-age children in the Netherlands. An analysis of 59 successive cases of perinatal death in singletons with birth weights below the 10th centile. J Perinat Med. 2010 May;38(3):311-8. PMID: 20121528

Westerhuis ME, Visser GH, Moons KG, van Beek E, Benders MJ, Bijvoet SM, van Dessel HJ, Drogtrop AP, van Geijn HP, Graziosi GC, Groenendaal F, van Lith JM, Nijhuis JG, Oei SG, Oosterbaan HP, Porath MM, Rijnders RJ, Schuitemaker NW, Sopacua LM, van der Tweel I, Wijnberger LD, Willekes C, Zuithoff NP, Mol BW, Kwee A. Cardiotocography plus ST-analysis of the fetal electrocardiogram versus cardiotocography only for intrapartum monitoring: a randomised controlled trial. Obstet Gynecol. 2010 Jun;115(6):1173-80. PMID: 20502287

Trefwoorden: perinatale sterfte, groeivertraging

Trefwoorden: foetale bewaking

Trefwoorden: perinatal audit, perinatale sterfte

Proefschriften Oosterbaan HP: copromotor voor: Promotie Dr. P.A.O.M. de Reu. Perinatal Mortality in the Netherlands: Perinatal audit and fetal biometry. Universiteit Maastricht, 29 april 2010.

Abstracts, voordrachten en posters Brandes M, van der Steen JO, Bokdam SB, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. Voordracht: Wanneer en waarom stoppen patiënten hun vruchtbaarheidsbehandeling. Symposium Psychosociale begeleiding tijdens vruchtbeerheidsbehandelingen. Organize Meeting Schering Plough, Zeist 27-3-2009. Hamilton CJ. GnRH antagonisten: “the JBZ experience”. Workshop GnRH agonisten versus GnRH antagonsiten. Houten 7-4-2009. Schenk A. Hamilton CJ. Impementatie GnRH antagonisten protocol in the kliniek. Workshop GnRH agonisten versus GnRH antagonsiten. Houten 7-4-2009.

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Brandes M, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. Heeft IVF de belofte waargemaakt. Ledenvergadering IVF-NVOG werkgroep. Utrecht, 17-4-2009. Brandes M, van der Steen JO, Bokdam SB, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. Wanneer en waarom stoppen patiënten hun vruchtbaarheidsbehandeling. Symposium IVF Paramedical Nederland (IPN), ’s-Hertogenbosch, 21-4-2009. Brandes M, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. Heeft IVF de belofte waargemaakt. Symposium IVF Paramedical Nederland (IPN), ’s-Hertogenbosch, 21-4-2009.


Brandes M, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. The relative contribution of in vitro fertilisation to the cumulative ongoing pregnancy rate in subfertile couples. ESHRE, Amsterdam, oral presentation. 30-6-2009. Human Reprod, volume 24 suppl 1, i71, 2009.

Hamilton CJ, Brandes M, Verzijden JC, de Weys NP, de Bruin JP, Nelen WL, Kremer JA. Is the fertility treatment itself a risk factor for early pregnancy loss? Proceeding 26th annual meeting ESHRE, Rome, 27-30 juni 2010 P-138, p165.

Brandes M, Hamilton CJ, van der Steen JO, de Bruin JP, Bots, RS, Nelen WL, Kremer JA. Evaluatie van behandeltrajecten bij mannelijke subfertiliteit in de dagelijkse praktijk Vereniging voor fertiliteitsstudie, Tilburg, 20-11-2009.

Thys SD, Coolen AL, Martens IR, Oosterbaan HP, Roovers JP, Mol BW, Bongers MY. Long term recurrence rates following Manchester Fothergill compared to vaginal hysterectomy for pelvic organ prolapse. IUAG, Como (It), 16-20 juni 2009.

Hamilton CJ Wat weten we tot nu toe over Q koorts en zwangerschap. Refereeravond kinderartsen Catharina ziekenhuis, Eindhoven, 18-5-2010. Hamilton CJ De Wording van een fertiliteitskliniek. Ter gelegenheid van de uitreiking van het ISO certificaat aan het centrum voor voorplantigsgeneeskunde, JBZ ’s-Hertogenbosch, 21-6-2010. Hamilton CJ. 25 jaar IVF Maastricht: de beginjaren. UMC Maastricht, 24-9-2010. Brandes M, Hamilton CJ, Verzijden JC, de Weys NP, de Bruin JP, Nelen WL, Kremer JA. Miskramen en vruchtbaarheidsbehandelingen. Symposium Jonge zwangerschap, Amsterdam 7-10-2010. Brandes M, Hamilton CJ, van der Steen JO, Bokdam SB, de Bruin JP, Nelen WL, Kremer JA. Poster: When and why do subfertile couples drop out from fertility care. ESHRE Amsterdam, 2009. Hum Reprod volume 24 suppl 1, i125, 2009

gynaecologie

Westerhuis MH, Kwee A, Zuithoff NP, van den Akker ES, van Beek E, van Dessel HJ, Drogtrop AP, van Geijn HP, Graziosi GC, van Lith JM, Nijhuis JG, Oei SG, Oosterbaan HP, Porath MM, Rijnders RJ, Schuitemaker NW, Wijnberger LD, Willekes C, Wouters MG, Visser GH, Mol BW, Moons KG. Poster: Prediction of neonatal metabolic acidosis in women with a cephalic positioned singleton term fetus. 30th annual meeting - the pregnancy meeting - SMFM, Chicago Illinois, USA, February 5th, 2010 Vijgen S, Westerhuis ME, van den Akker SA, van Beek E, Bolte AC, van Dessel HJ, Drogtrop AP, van Geijn HP, Graziosi GC, van Lith JM, Nijhuis JG, Oei SG, Oosterbaan HP, Opmeer BC, Porath MM, Rijnders RJ, Schuitemaker NW, Willekes C, Visser GH, Mol BW, Moons KG. Poster: Cost-effectiveness of cardiotocography plus ST-analysis of the fetal electrocardiogram compared to cardiotocography only in the prevention of cerebral palsy: preliminary results. 30th annual meeting - the pregnancy meeting - SMFM, Chicago Illinois, USA, February 5th, 2010. Gaugler-Senden IP, Duivenvoorden HJ, Filius A, de Groot CJ, Steegers EA, Passchier J. Poster: Long term maternal psychosocial effects after severe, early onset preeclampsia 56th annual scientific meeting of the Society of Gynecologic Investigation, Glasgow UK, 18-21 maart 2009.

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Oosterbaan HP. Gynaecologie. Bijeenkomst voor eerstelijns zorgverleners ter gelegenheid opening polikliniek Nieuwkuijk, Nieuwkuijk. 19 maart 2009.

Oosterbaan HP. Zorgpad verloskundige zorg en geboorteplan. VSV, Den Bosch, 25 mei 2010.

Oosterbaan HP. Hormoon Substitutie Therapie. FTO Vught, 6 april 2009.

Oosterbaan HP. Massive Obstetric Haemorrhage. Managing Obstetric Emergencies & Trauma Course (MOET), Riel, 11 juni 2010.

Oosterbaan HP. Resuscitation and peri-mortem caesarean section. MOET course, Riel, 17 september 2009.

Oosterbaan HP. Herpes genitalis en zwangerschap. VSV, Den Bosch, 28 september 2010.

Oosterbaan HP. Massive Obstetric Haemorrhage. MOET course, Riel, 18 september 2009,

Kerkhof MH Blijft de generalist bestaan? Voordracht Domus Medica opleiders gynaecologie, mei 2009

Oosterbaan HP. Zin en onzin over de pil – een update. Masterclass Gynaecologie, Soestduinen, 14 en 29 oktober 2009.

Kerkhof MH Vulva pathologie Voordracht kaderopleiding huisartsen, september 2009

Publicaties (niet pubmed) Brandes M, Hamilton CJ, Bergevoet KA, de Bruin JP, Nelen WL, Kremer JA. Prevalentie van meerlingen ten gevolge van vruchtbaarheidsbehandelingen. Ned Tijdschr Obstet Gynaecol. 122:239-243, 2009

FJ, Kwee A, Schuitemaker NW, Mol BW, van Rhenen DJ, Duvekot JJ. Well being of Obstetric patients on Minimal Blood transfusions (WOMB trial). BMC Pregnancy Childbirth. 2010 Dec 16;10(1):83.

Ennink TA, Hamilton CJ, Kemperman FA. Heeft behandeling van subklinische hypothyroidie bij zwangere vrouwen een positief effect op de neurologische ontwikkeling van het kind. Ned Tijdschr Obstet Gynaecol 2010, 123:47-48

Westerhuis ME, Visser GH, Moons KG, van Beek E, Benders MJ, Bijvoet SM, van Dessel HJ, Drogtrop AP, van Geijn HP, Graziosi GC, Groenendaal F, van Lith JM, Nijhuis JG, Oei SG, Oosterbaan HP, Porath MM, Rijnders RJ, Schuitemaker NW, Sopacua LM, van der Tweel I, Wijnberger LD, Willekes C, Zuithoff NP, Mol BW, Kwee A. Cardiotocography plus ST analysis of fetal electrocardiogram compared with cardiotocography only for intrapartum monitoring: a randomized controlled trial. Obstet Gynecol. 2010 Jun;115(6):1173-80.

Prick BW, Steegers EA, Jansen AJ, Hop WC, Essink-Bot ML, Peters NC, Uyl-de Groot CA, Papatsonis DN, Akerboom BM, Metz GC, Bremer HA, van Loon AJ, Stigter RH, van der Post JA, van Alphen M, Porath M, Rijnders RJ, Spaanderman ME, Schippers DH, Bloemenkamp KW, Boers KE, Scheepers HC, Roumen

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Kaandorp JJ, Benders MJ, Rademaker CM, Torrance HL, Oudijk MA, de Haan TR, Bloemenkamp KW, Rijken M, van Pampus MG, Bos AF, Porath MM, Oetomo SB, Willekes C, Gavilanes AW, Wouters MG, van Elburg RM, Huisjes AJ, Bakker SC, van Meir CA, von Lindern J, Boon J, de Boer IP, Rijnders RJ, Jacobs CJ, Uiterwaal CS, Mol BW, Visser GH, van Bel F, Derks JB. Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study. BMC Pregnancy Childbirth. 2010 Feb 18;10:8. Kooper AJ, Faas BH, Feuth T, Creemers JW, Zondervan HH, Boekkooi PF, Quartero RW, Rijnders RJ, van der Burgt I, van Kessel AG, Smits AP. Detection of chromosome aneuploidies in chorionic villus samples by multiplex ligation-dependent probe amplification. J Mol Diagn. 2009 Jan;11(1):17-24. Kerkhof MH 2 ingezonden brieven: “een beetje tijd” en “solliciteren”. Medisch Contact 24-9-2010 Kerkhof MH 1 praktijkperikel: “zwanger bij IQ < 50. Medisch Contact 24-9-2010

gynaecologie

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INTENSIVE CARE GENEESKUNDE Wetenschappelijke publicaties Van Kuilenburg JT, van Niekerk J, Sinnige H, de Jager CP. A woman with a swollen neck. Neth J Med. 2009 Oct;67(9):308-9. PMID: 19841489

de Jager CP, Rutten MJ. Embolization as treatment of choice for bleeding peptic ulcers in high-risk patients. Dig Surg. 2009;26(1):37-42. PMID: 19155626

De Wit NC, de Jager CP, Meekelenkamp JC, Schoorl M, van Gageldonk-Lafeber AB, Leenders AC, Kusters R, Wever PC. Markers of infection in inpatients and outpatients with acute Q-fever. Clin Chem Lab Med. 2009;47(11):1407-9. PMID: 19778289

Van de Veerdonk FL, de Jager CP, Schellekens JJ, Huijsmans CJ, Beaumont F, Hermans MH, Wever PC. Legionella pneumophila DNA in serum samples during Legionnaires’ disease in relation to C-reactive protein levels. Eur J Clin Microbiol Infect Dis. 2009 Apr;28(4):371-6. PMID: 18855027

De Jager CP, de Wit NC, Weers-Pothoff G, van der Poll T, Wever PC. Procalcitonin kinetics in Legionella pneumophila pneumonia. Clin Microbiol Infect. 2009 Nov;15(11):1020-5. PMID: 19438643

Rozendaal FW, Spronk PE, Snellen FF, Schoen A, van Zanten AR, Foudraine NA, Mulder PG, Bakker J; UltiSAFE investigators. Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: a centre randomised, cross-over, open-label study in the Netherlands. Intensive Care Med. 2009 Feb;35(2):291-8. PMID: 18949456

Van Vugt R, Bosscha K, Olsman J, and Jager GJ, de Jager CP. Management of hepatic trauma: a 9-year experience in ’s-Hertogenbosch. Acta Chir Belg. 2009 Jan-Feb;109(1):42-6. PMID: 19341194 Van Vugt R, Bosscha K, van Munster IP,

intensive care geneeskunde

de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional

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infection markers in an emergency care unit. Crit Care. 2010;14(5):R192. PMID: 21034463 Simons KS, Pickkers PP, Oyen WJG van der Hoeven JG. F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected of infection. Intensive Care Med. 2010 Mar;36(3):504-11. PMID: 19847397 Bisschops LL, Hoedemaekers CW, Simons KS, van der Hoeven JG. Preserved metabolic coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest. Crit Care Med. 2010 Jul;38(7):1542-7. PMID: 20453643

Abstracts, voordrachten en posters De Jager CP, de Wit NC, Weers-Pothoff G, van der Poll T, Wever PC. Poster: Procalciton Kinetics in Legionella pneumophila pneumonia. Intensivisten dagen 2009.

Laheij R, de Jager CP, Markese M, van der Spoel JL, van Oijen M. Poster: The consequences of large gastric volumes after start of enteral feeding in critically ill patients. GASTRO Londen, 2009.

De Jager CP. Voordracht: Predictive value of procalcitonin in legionella infections. Procalcitonin in the ICU- to do or not to do? Symposium Brahm, Utrecht, 2009.

Bisschops L, Hoedemaekers CW, Simons K, van der Hoeven JG. Abstract: Cerebrovascular reactivity during hypothermia after cardiac arrest. Annual congress of Dutch Intensive Care Society, Ede 2009.

De Jager CP. Thema conferentie VMS: vroege herkenning en behandeling van de vitaal bedreigde patiënt, Domus Medica, Dagvoorzitter 2009. De Jager CP. Poster: Increased unplanned extubations after implmentation of analgosedation. European Society of Intensive Care Medicine, Barcelona, oktober 2010.

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Bisschops L, Hoedemaekers CW, Simons K, van der Hoeven JG. Abstract: Cerebral blood flow in hypothermic and normothermic patients after cardiac arrest. Annual congress of Dutch Intensive Care Society, Ede, 2009. De Jager CP. Voordracht: Dynamisch licht op de Intensive Care.


Health to Business club JBZ Philips Eindhoven, november 2010. Veeken S, de Jager CP. Een nieuw volkslied; ritmestoornissen en pericardvocht als eerste uitingen van een primair cardiaal non-hodgkin lymfoom. Lunchbespreking Intensive Care, maart 2009. Baten A, Rozendaal FW, de Jager CP. The X-factor; pulmonale actinomycose bij een immuungecompromiteerde patiënte. Lunchbespreking Intensive Care, februari 2009. Van Gulik J, van Dorsten F, de Jager CP. Yellow Submarine; over fulminant leverfalen. Lunchbespreking Intensive Care, mei 2009. Evers J, Rozendaal FW, de Jager CP. Centrale pontine myelinolyse door een te snelle natriumcorrectie. Lunchbespreking Intensive Care, januari 2009.

De Jager CP. Invasieve Aspergillose. Lunchbespreking intensive care, 2009. De Jager CP. Thuis opgelopen longontsteking. Lunchbespreking intensive care, 2009. De Jager CP. De gevolgen van maagretentie voor de IC-patient. Lunchbespreking intensive care, 2009. De Jager CP. Het voorschrijven en stoppen van antibiotica op geleide van het procalcitonine. Lunchbespreking intensive care, 2010. Paling AJ Voordracht: Ervaring met GHB-onttrekking op IC. Opening GHB-monitor NISPA, Nijmegen, november 2010.

Publicaties (niet pubmed) Salet GA, Lammers JL, Korst MB, Beaumont F, Rozendaal FW, de Jager CP. Percutaneous mechanical thrombectomy in recurrent massive pulmonary embolism. Netherlands Journal of Critical Care, volume 14, no 6, december 2010. De Groot AC, van Meurs T, de Jager CP, Bosma J, Wever PC, Stoof TJ. Necrotiserende fasciitis: kliniek, diagnostiek en behandeling. Nederlands tijdschrift voor dermatologie en venerologie, volume 19, nummer 3, maart 2009. De Groot AC, van Meurs T, de Jager CP, Bosma J, Wever PC. Necrotiserende fasciitis: casuïstiek. Nederlands Tijdschrift voor dermatologie en venerologie, 2009.

intensive care geneeskunde

Lips DJ, van Leuken M, de Jager CP. “Goedaardig” vena cava superior syndroom, bijzondere ziektebeelden op de intensive care. Cura, april 2009. De Jager CP, van Leuken M, Wever PC. Phelephlebitis; septische tromboflebitis van de poortader en mesenteriaal vaten, bijzondere ziektebeelden op de intensive care. Cura, juli 2009. Van Kuilenburg JT, Wever PC, de Jager CP. Morbus strangularis, bijzondere ziektebeelden op de intensive care. Cura, december 2009.

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INTERNE GENEESKUNDE Wetenschappelijke publicaties Herbers AH, Verbruggen B, Van de Veerdonk F, Van Kraaij M, Blijlevens NM, Novakova IR. Misleading one-stage coagulation factor assay during rFVIIa treatment in lupus patient. Haemophilia. 2009 Sep;15(5):1164-6. PMID: 19601985 Van der Velden WJ, Herbers AH, Blijlevens NM. Palifermin in allogeneic HSCT: many questions remain. Bone Marrow Transplant. 2009 Jan;43(1):85-6. PMID: 18762763 van Poppel PC, Stehouwer CD, Beutler JJ, Korst MB, Beerlage HP, Hoogeveen EK. Hyperchloremic metabolic acidosis in a patient with an ureteroileostomy according to Bricker. Ned Tijdschr Geneeskd. 2009 May 23;153(21):1024-8. PMID: 19757757 van Poppel PC, Stehouwer CD, Beutler JJ, Korst MB, Beerlage HP, Hoogeveen EK. Hyperchloremic metabolic acidosis in a patient with an ureteroileostomy according to Bricker. Ned Tijdschr Geneeskd. 2009;153:B317. Dutch. PMID: 19785899 Anderwald C, Ankersmit HJ, Badaoui A, Beneduce L, Buko VU, Calo LA, Carrero JJ, Chang C-Y, Chang K-C,

interne geneeskunde

Chen Y-J, Cnotliwy M, Costelli P, Crujeiras AB, Cuocolo A, Davis PA, de Boer OJ, Ebenbichler CF, Erridge C, Fassina G, Felix SB, García-Gomez MC, GuerreroRomero F, Haider DG, HeinemannA, Herda LR, Hoogeveen EK, Hörl WH, Iglseder B, Huang K-C, Kaser S, Kastrati A, Kuzniatsova N, Latella G, Lichtenauer M, Lin Y-K, Lip GYH, Lu N-H, Lukivskaya O, Luschnig P, Maniscalco M, Martinez JA, MüllerKrebs S, Ndrepepa G, Nicolaou G, Peck-Radosavljevic M, Penna F, Pinto X, Reiberger T, Rodriguez-Moran M, Schmidt A, Schwenger V, Spinelli L, Starkel P, Stehouwer CDA, Stenvinkel P, Strasser P, Suzuki H, Tschoner A, van der Wal AC, Vesely DL, Wen C-J, Wiernicki I, Zanninelli G and Zhu Y. Research update for articles published in EJCI in 2008. Eur J Clin Invest. 2010; 40: 770-790. PMID: 20698878 Hoogeveen EK, Stehouwer CD. Exclusion of a case-control study from meta-analysis. Mayo Clin Proc. 2009; 84: 561. PMID: 19483176 Sleegers MJ, Beutler JJ, Hardon W, Berden JH, Hollander DA, Dautzenberg PL, Hoogeveen EK. Reversible rapidly progressive dementia induced by valproate in a patient with systemic lupus erythematosus.

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J Am Geriatr Soc. 2010; 58: 799-801. PMID: 20398172 van der Horn G, Ranschaert ER, Dubelaar IJ, van Munster IP. An adult with vague abdominal complaints and atypical colonoscopic findings. Neth J Med. 2010 Aug;68(1):324-7. No abstract available. PMID: 20739731 Van Rossum LG, van Rijn AF, van Munster IP, Jansen JB, Fockens P, Laheij RJ, Dekker E. Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests. Neth J Med. 2009 May;67(5):182-6. PMID: 19581668 Van den Broek FJ, de Graaf EJ, Dijkgraaf MG, Reitsma JB, Haringsma J, Timmer R, Weusten BL, Gerhards MF, Consten EC, Schwartz MP, Boom MJ, Derksen EJ, Bijnen AB, Davids PH, Hoff C, van Dullemen HM, Heine GD, van der Linde K, Jansen JM, Mallant-Hent RC, Breumelhof R, Geldof H, Hardwick JC, Doornebosch PG, Depla AC, Ernst MF, van Munster IP, de Hingh IH, Schoon EJ, Bemelman WA, Fockens P, Dekker E. Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TRENDstudy). BMC Surg. 2009 Mar 13;9:4. PMID: 19284647 Kuiper EM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen TJ, Haagsma EB, Houben MH, Witteman BJ, van Erpecum KJ, van Buuren HR; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009 Apr;136(4):1281-7. PMID: 19208346

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van Vugt R, Bosscha K, van Munster IP, de Jager CP, Rutten MJ. Embolization as treatment of choice for bleeding peptic ulcers in high-risk patients. Dig Surg. 2009;26(1):37-42. PMID: 19155626 Penne EL, van der Weerd NC, van den Dorpel MA, Grooteman MP, Lévesque R, Nubé MJ, Bots ML, Blankestijn PJ, ter Wee PM; CONTRAST Investigators (Hoogeveen EK). Short-term effects of online hemodiafiltration on phosphate control: a result from the randomized controlled Convective Transport Study (CONTRAST). Am J Kidney Dis. 2010 Jan;55(1):77-87. PMID: 19962805 Penne EL, van der Weerd NC, Blankestijn PJ, van den Dorpel MA, Grooteman MP, Nubé MJ, Ter Wee PM, Lévesque R, Bots ML; CONTRAST investigators. (Hoogeveen EK). Role of residual kidney function and convective volume on change in beta2-microglobulin levels in hemodiafiltration patients. Clin J Am Soc Nephrol. 2010;5:80-86. PMID: 19965537 van Kuilenburg JT, van Niekerk J, Sinnige H, de Jager CP. A woman with a swollen neck. Neth J Med. 2009 Oct;67(9):308-9. PMID: 19841489 Bax L, Mali WP, Beutler JJ. Stenting in patients with atherosclerotic renal artery stenosis Ned Tijdschr Geneeskd. 2010;154(23):A1607. PMID: 20619027 Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, Braam B, Huysmans FT, Schultze Kool LJ, Rutten MJ, Doorenbos CJ, Aarts JC, Rabelink TJ, Plouin PF, Raynaud A, van Montfrans GA, Reekers JA, van den Meiracker AH, Pattynama PM, van de Ven PJ, Vroegindeweij D, Kroon AA, de Haan MW, Postma CT,


Beutler JJ. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med. 2009 Jun 16;150(12):840-8, W150-1. PMID: 19414832

Boquoi A, Jover R, Chen T, Pennings M, Enders GH. Transgenic expression of VEGF in intestinal epithelium drives mesenchymal cell interactions and epithelial neoplasia. Gastroenterology 2009; 136:596-606. PMID: 19056388

De Mast Q, Beutler JJ. The prevalence of atherosclerotic renal artery stenosis in risk groups: a systematic literature review. J Hypertens. 2009 Jul;27(7):1333-40. PMID: 19365285

van Schaik PM, Hermans E, van der Linden JC, Pruijt JF, Ernst MF, Bosscha K. Micrometastases in stages I and II colon cancer are a predictor of the development of distant metastases and worse disease-free survival. Eur J Surg Oncol 2009; May;35(5):492-6. PMID: 18775627

Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Grönhagen-Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Süleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wüthrich RP, Gottlow M, Johnsson E, Zannad F; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009 Apr 2;360(14):1395-407. PMID: 19332456 Van Dijk S, Scharloo M, Kaptein AA, Thong MS, Boeschoten EW, Grootendorst DC, Krediet RT, Dekker FW; NECOSAD Study Group, Apperloo AJ, Bijlsma JA, Boekhout M, Boer WH, van der Boog PJ, Büller HR, van Buren M, de Charro FT, Doorenbos CJ, van den Dorpel MA, van Es A, Fagel WJ, Feith GW, de Fijter CW, Frenken LA, van Geelen JA, Gerlag PG, Grave W, Gorgels JP, Huisman RM, Jager KJ, Jie K, Koning-Mulder WA, Koolen MI, Hovinga TK, Lavrijssen AT, Luik AJ, van der Meulen J, Parlevliet KJ, Raasveld MH, van der Sande FM, Schonck MJ, Schuurmans MM, Siegert CE, Stegeman CA, Stevens P, Thijssen JG, Valentijn RM, Vastenburg GH, Verburgh CA, Vincent HH, Vos PF. Patients’ representations of their end-stage renal disease: relation with mortality. Nephrol Dial Transplant 2009 Oct;24(10):3183-5. PMID: 19383834

interne geneeskunde

Dassen AE, Lips DJ, Hoekstra CJ, Pruijt JF, Bosscha K. FDG-PET has no definite role in pre-operative imaging in gastric cancer. Eur J Surg Oncol 2009;May;35(5):449-55. PMID: 19147324 van Steenbergen LN, Rutten HJ, Creemers GJ, Pruijt JF, Coebergh JW, Lemmens VE. Large age and hospital-dependent variation in administration of adjuvant chemotherapy for stage III colon cancer in southern Netherlands. Ann Oncol. 2010 Jun;21(6):1273-8. PMID: 19880434 van Herk-Sukel MP, van de Pll-Franse LV, Lemmens VE, Vreugdenhil G, Pruijt JF, Coebergh JW, Herings RM. New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System. Eur J Cancer 2010;46:395-404. PMID: 19811904 Berger LP, Scheffer RC, Weusten BL, Seldenrijk CA, de Bruin PC, Timmer R, Stolk MF. The additional value of EUS-guided Tru-cut biopsy to EUS-guided FNA in patients with mediastinal lesions. Gastrointest Endosc. 2009 May;69(6):1045-51. PMID: 19249038

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Frankhuisen R, Van Herwaarden MA, Scheffer RC, Hebbard GS, Gooszen HG, Samsom M. Increased intragastric pressure gradients are involved in the occurrence of acid reflux in gastroesophageal reflux disease. Scand J Gastroenterol. 2009;44(5):545-50. PMID:19191069 Krediet RT, Smit W, Coester AM, Struijk DG. Dry body weight and ultrafiltration targets in peritoneal dialysis. Contrib Nephrol. 2009;163:90-5. PMID: 19494600 Krediet RT, Sampimon DE, Vlijm A, Coester AM, Struijk DG, Smit W. Biological markers in the peritoneal dialysate effluent: are they useful. Contrib Nephrol. 2009;163:54-9. PMID: 19494595 Coester AM, Smit W, Struijk DG, Krediet RT. Fluid transport with time on peritoneal dialysis: the contribution of free water transport and solute coupled water transport. Contrib Nephrol. 2009;163:22-6. PMID: 19494591 Coester AM, Smit W, Struijk DG, Krediet RT. Peritoneal function in clinical practice: the importance of follow-up and its measurement in patients. Recommendations for patient information and measurement of peritoneal function. NDT Plus. 2009 Apr;2(2):104-110. PMID: 19461865 Dorresteijn MJ, Visser T, Cox LA, Bouw MP, Pillay J, Koenderman AH, Strengers PF, Leenen LP, van der Hoeven JG, Koenderman L, Pickkers P. C1-esterase inhibitor attenuates the inflammatory response during human endotoxemia. Crit Care Med. 2010 Nov;38(11):2139-45. PMID: 20693886

50

Draisma A, Dorresteijn MJ, Bouw MP, van der Hoeven JG, Pickkers P. The role of cytokines and inducible nitric oxide synthase in endotoxemia-induced endothelial dysfunction. J Cardiovasc Pharmacol. 2010 Jun;55(6):595-600. PMID: 20224425 Dorresteijn MJ, Draisma A, van der Hoeven JG, Pickkers P. Lipopolysaccharide-stimulated whole blood cytokine production does not predict the inflammatory response in human endotoxemia. Innate Immun. 2010 Aug;16(4):248-53. PMID: 19710091 Boerjan M, Bluyssen SJ, Bleichrodt RP, van Weel-Baumgarten EM, van Goor H. Work-related health complaints in surgical residents and the influence of social support and job-related autonomy. Med Educ. 2010 Aug;44(8):835-44. PMID: 20633223 Trefwoorden: Opleidingsklimaat, arts-assistent.

Clement DS, Postma G, Rothova A, Grutters JC, Prokop M, de Jong PA. Intraocular sarcoidosis: association of clinical characteristics of uveitis with positive chest highresolution computed tomography findings. British journal of Ophthalmology 2010 Feb;94(2):219-22 PMID 19713200 Esselink AC, de Ruijter AM, Daniels MC. Application of NHG guidelines in patients referred for stable chest pain syndromes. Neth Heart J 2010; 18:178-82 PMID 20428415 Scheffer RC, Bredenoord AJ, Hebbard GS, Smout AJ, Samsom M. Effect of proximal gastric volume on hiatal hernia.


Neurogastroenterol Motil. 2010 May;22(5):552-6, e120. PMID: 20105278 Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; Dutch-Belgium Cooperative Group HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 ; 28 (19) :3160-6. PMID: 20516439 Labar B, Suciu S, Willemze R, Muus P, Marie JP, Fillet G, Berneman Z, Jaksic B, Feremans W, Bron D, Sinnige H, Mistrik M, Vreugdenhil G, de Bock R, Nemet D, Gilotay C, Amadori S, De Witte T; on behalf of the EORTC Leukemia Group. Dexamethasone versus prednisolone for adult acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma LBL) patients - final results of the ALL-4 randomized, Phase III trial of the EORTC Leukemia Group. Haematologica 2010; 95(9):1489-95. PMID: 20378563 Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian HematoOncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. PMID: 19880501 Tielemans MM, Eikendal T, Jansen JB, van Oijen MG.

interne geneeskunde

Identification of NSAID users at risk for gastrointestinal complications: a systematic review of current guidelines and consensus agreements. Drug Saf. 2010 Jun 1;33(6):443-53. PMID: 20486727 Kuiper EM, Hansen BE, De Vries RA, Den OudenMuller JW, Van Ditzhuijsen ThJ, Haagsma EB et al. Improved diagnosis of patients with PBC that have a biochemical response to ursodeoxycholic acid. Gastroenterology 2009; 136:1281-7. PMID 19208346 Ramakers BP, Pickkers P. Adenosine-mediated attenuation of the innate immune response for only those who need it? The tailored potential of pentoxifylline. Shock. 2010 Jul;34(1):105-6. PMID: 20016402 Van den Boogaard M, Ramakers BP, van Alfen N, van der Werf SP, Fick WF, Hoedemaekers CW, Verbeek MM, Schoonhoven L, van der Hoeven JG, Pickkers P. Endotoxemia-induced inflammation and the effect on the human brain. Crit Care. 2010;14(3):R81. PMID: 20444270 Pillay J, Ramakers BP, Kamp VM, Loi AL, Lam SW, Hietbrink F, Leenen LP, Tool AT, Pickkers P, Koenderman L. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010 Jul;88(1):211-20. PMID: 20400675 Herbers AHE, Feuth T, Donnelly JP, Blijlevens NM. Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy. Ann Oncol.2010 Aug;21(8):1706-11. PMID: 20089560

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Tieleman AA, Knoop H, van de Logt AE, Bleijenberg G, van Engelen BG, Overeem S. Poor sleep quality and fatigue but no excessive daytime sleepiness in myotonic dystrophy type 2. J Neurol Neurosurg Psychiatry. 2010 Sep;81(9):963-7. PMID: 20798200

Tieleman AA, den Broeder AA, van de Logt AE, van Engelen BG. Strong association between myotonic dystrophy type 2 and autoimmune diseases. J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1293-5. PMID: 19864666

Boeken Herbers AH, De Pauw P. Managing infections in patients with acute leukemia and febrile neutropenia. Managing Infections in Patients with Hematological Malignancies. Edited by Michael Kleinberg. New York, NY, United States: Humana Press - Springer New York, 2010. ISBN: 978-1-58829-986-4.

Abstracts, voordrachten en posters Bons E, Herbers AH, van der Velden WJ. Voordracht: Two cases of pneumocystis jirovecii pneumonia during R-CHOP-14 for non-Hodgkin lymphoma. NIV dagen april 2009. Herbers AH, Donnelly JP, Blijlevens NM. Poster: Influence of rKGF on intestinal mucosal damage measured by citrulline in autologous haematopoietic stem cell transplant recipients treated after BEAM: a safety and efficacy study. EBMT maart 2010.

erythematosus. Supplement Neth J Med. Abstractbook, 21e internistendagen, 2009, A75. (NIV award: best abstract/presentation) Dieker H, Dorresteijn MJ, Hoogeveen EK, Hollander AA. The wolf and the white raven: diffuse alveolar hemorrhage in SLE. Supplement Neth J Med. Abstractbook, 21e internistendagen, 2009, A46. (NIV award: best abstract/presentation)

Kampschreur LM, Hoogeveen EK, Beutler JJ, Akker

Ocak G, Halbesma N, le Cessie S, Hoogeveen EK,

op den JW, Beems T, Seveaux de RG. A haemodialysis patient with back pain. Supplement Neth J Med. Abstractbook, 20e internistendagen, 2009, A245.

van Dijk S, Kooman J, Dekker FW, Krediet RT, Boeschoten EW, Verduijn M. Hemodialysis catheters increase mortality as compared to shunts especially in elderly patients. American Society of Nephrology, Denver, USA, November 2010.

Sleegers MJ, Beutler JJ, Hardon W, Berden JH, Dautzenberg PL, Hoogeveen EK. Reversible cognitive and gait impairment induced by valproate in a patient treated for systemic lupus

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Hoogeveen EK, de Mutsert R, Halbesma N, Dekker FW, Boeschoten EW for the Netherlands Cooperative Study on the Adequacy of Dialysis-2 (NECOSAD) Study Group.


Obesity is a risk factor for mortality, especially among younger dialysis patients. American Society of Nephrology, Denver, USA, 18 november 2010. Kemperman FA. Androgeen deprivatie: effecten buiten de prostaat. Regionale refereeravond urologie JBZ, ’s-Hertogenbosch, februari 2010. van der Hilst JC, Kemperman FA. Abstract: Myxoma cordis: a rare cause of fever of unknown origin. Abstractboek NIV 21e Internistendagen 2009; blz. 123: abstractnr. 232. Ennink TA, Hamilton CJ, Kemperman FA. PICO Bello – Heeft behandeling van subklinische hypothyreoïdie bij zwangere vrouwen een positief effect op de neurologische ontwikkeling van het kind. Ned Tijdschr Obstr Gyn 2010 Feb; 121(2): blz 23-25. Boerjan M, Liem S, Renders N, Lestrade P, Bouter KP. Q-fever endocarditis: a diagnosis easily missed with serious consequences. Abstractenboek NIV (internistendagen): Infectious diseases Case reports.

Lips DL, Koebrugge B, Liefers GJ, Putter H, Smit V, van der Linden JC, Pruijt HF, van de Velde CJH, Bosscha K. The role of micro-metastases on prognosis and survival in stage I-II colon cancer patients- the EnRoute+ study. Abstr. Nr. 324 ESSO 2010 Bordeaux Jansen HJ, Pruijt JFM, de Jongh-Leuvenink J, Bouter KP, Lestrade P. Multiple hemoglobinopathies and glucose-6phosphate dehydrogenase deficiency in a patient with diabetes mellitus de novo: usefulness of glycosylated haemoglobin levels? Internistendagen, Maastricht, april 2009. Farré R, Blondeau K, Clement D, Vicario M, Cardozo L, Vieth M, Mertens V, Pauwels A, Jimenez M, Tack J, Sifrim D. Poster: Evaluation of Esophageal Mucosa Integrity “In Vivo”. Validation of Basal Intraluminal Impedance Measurements to Assess Non- Erosive Changes Induced by Esophageal Acid Exposure in Rabbit and Healthy Human Subjects. Digestive Disease Week, 4 Mei 2010. Lestrade P. Botten en buffers. Internisten, orthopeden, reumatologen en arts-assistenten, Boxtel, 12 maart 2009.

Trefwoorden: Q-koorts, endocarditis.

Toonen FAJ, Bouter KP. A 36-year-old patient with a congenital diabetes mellitus may stop his use of insulin. Internistendagen, Maastricht, april 2009. van Warmerdam LJC, Schiphorst PP, Nieboer P, Dercksen MW, Nijziel MR, Pruijt JFM, de Jongh FE, Creemers GJM. Cardiac safety of non-pegylated liposomal doxorubicine in combination with docetaxel as 1st line treatment in locally-advanced or metastatic HER-2 negative breast cancer (MYOTAX study). Abstr.nr. 5068. ESMO/ECCO 2009

interne geneeskunde

Lestrade P. Prostaatca en botten. Urologen, endocrinologen. Waalwijk, 29 september 2009. Lestrade P. 3 x voordracht Q-koorts voor patiënten. Februari/april 2010. Pruijt J. Mutatieanalyse voor therapeutische doeleinden binnen de oncologie. Nederlandse Internistendagen Maastricht, april 2009.

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Pruijt J. (Nieuwe) behandelmogelijkheden ITP. Nederlandse avond ASCO 2009. Orlando USA, 01 Juni 09. Pruijt J. Epoëtine anno 2009 bij solide tumoren- is er nog een indicatie? Nederlandse Oncologiedagen. Papendal, nov 2009. Pruijt J. “High Lights ASH 2009”. ASH review. Utrecht, 16 december 2009 Pruijt J. Voordracht voor de patiëntenvereniging van M. Waldenstrom. ’s-Hertogenbosch, 27 mei 2010 Pruijt J. Voordracht: High-lights World Congres Gastro-intestinal Cancer Barcelona 2010. IKZ symposium gastro-enterologie. 05 juli 2010 Pruijt J. Steeds meer farmaco-epidemiologie. Symposium Leren door registreren. Ter ere van 55 jaar IKZ kankerregistratie. Eindhoven, 11 november 2010. Smilde T. Welkom in de wereld van de oncologie. Voordracht voor huisartsen. Maart 2009. Smilde T. Het triple negatief mammacarcinoom. Bossche mammadagen. Juni 2009. Smilde T. Behandeling van het testiscarcinoom. Juni 2009.

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Smilde T. KPC necrologie. September 2009. Smilde T. Behandeling van het blaascarcinoom met chemotherapie. December 2009. Smilde T. Als je lijf op de foto moet. Nascholing radiologisch laboranten. Februari 2010. Smilde T. Begeleidingsmodel, opleiden in de klinische praktijk. Maart 2010. Smilde T. Het niet heldercellig niercelcarcinoom en bijzondere blaastumoren. Juni 2010. Smilde T. Het secundair gemetastaseerd mammacarcinoom, hormonale therapie? Juni 2010. Beutler JJ. Voordracht: ‘Vasculair risico begrijpen: De wetenschap in praktijk’, Diagnostiek naar nierarteriestenose: is opsporen en behandelen ook genezen?’ Amsterdam, 31 januari 2009. Beutler JJ. Voordracht: STAR trial: Efficacy and Safety of Stenting in Atherosclerotic Renovascular Disease. World Congress Nephrology, Milaan, 24 mei 2009. Tielemans MM, Van Oijen MG, Mulder CJ, Vos CJ, Lems WF. Poster: Similar effect of Esopramazole on upper


gastrointestinal symptoms in high upper GI risk versus average risk NSAID users. UEGW okt 2010. Herbers AH. Voordracht: Bloedaanmaak en aanverwante bloedziekten. Scholing Hematologie, oktober 2010.

Herbers AH. Voordracht: Bloedziekten en gebruik hematopoetische groeifactoren. Voor oncologieverpleekundigen, Oud Empel, oktober 2010.

Publicaties (niet pubmed) Ten Oever J, Herbers AH, Verhoef LH, Van den Wall Bake AW. Streptococcus equi subspecies zooepidemicus bacteremia as First Manifestation of Hairy Cell Leukemia. Infectious Diseases in Clinical Practice Nov 2009; 17: 407-408. Herbers AH, Feuth T, Donnelly JP, Blijlevens NM. Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy. Annals of Oncology 2010. Vol 21, nr 8: 1706-1711. Willemsen DJ, Bons E, Herbers AH, Mackenzie MA, Van Spronsen DJ, Van der Velden WJ. Pneumocystis jirovecii-pneumonia in non-hodgkin lymphoma patients treated with R-CHOP. Tijdschrift voor infectieziekten 2010. Vol 5, nr 4, 152-156. Hoogeveen EK, Broekman JM, Janssen RW. Induction of eruptive benign melanocytic nevi after kidney transplantation. Clin Dermatol. 2009; 1: 29-30. Kampschreur L, Hoogeveen EK, op den Akker JW, Beutler JJ, Beems T, Dorresteijn LD, de Sévaux RG. A haemodialysis patient with back pain: brown tumour as a cause of spinal cord compression under cinacalcet therapy. Nephrol Dial Transplant Plus. 2010; 3: 291-295.

interne geneeskunde

Jansen JB, van Rossum LG, Laheij RJ. Ter discussie. Bevolkingsonderzoek naar dikke darmkanker. Bij voorkeur met een immunologische test op fecaal occult bloed. Ned Tijdschr Geneeskd. 2009; 11 juli; 153 (28). Van Lieshout AW, Kampschreur LM, de Jong J, Sinnige HA. Anemie met een Chinees tintje. Ned Tijdschr Hematol 2009; 6: 194-8. Sonneveld P, Zweegman S, Vellenga E, Wittebol S, Sinnige HA, Meijer E, Minnema MC, Lokhorst HM. Richtlijn behandeling plasmacelaandoeningen anno 2010. Ned tijdschrift Hematologie 2010; 7:41-52. Van Rossum LG, van Rijn AF, van Munster IP, Jansen JB, Fockens P, Laheij RJ, Dekker E. Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests. Neth J Med. 2009; 67 (5): 182-86. Wever PC, Arts CH, Groot CA, Lestrade PJ, Koning OH, Renders NH. Screening op chronische Q-koorts bij symptomatische patiënt met aneurysma of prothese van de aorta. Ned Tijdschr Geneeskd. 2010; 154:A2122. Lips DJ, van der Linde JC, Pruijt JF, Bosscha K, Liefers GJ, Smit VT, van de Velde CJ. Betere stadiering darmkanker nodig. Medisch Contact 2010;65:484-487.

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Schipperus MR, Koene H, Zwaginga JJ, te Boekhorst PA, Vreugdenhil G, Pruijt JF, Novotny VM, van Pampus EC, Fijnheer R. Nederlandse richtlijn voor de diagnose en behandeling van immuun trombocytopenische purpura bij volwassenen. Ned Tijdschr Hematol. 2010;7:59-68 Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, Van Groeningen CJ, Sinnige HA, et al. Chemotherapy, Bevacizumab, and Cetuximab in metastatic colorectal cancer. N Engl J Med 2009; 360: 563-72. Robben SH, Sleegers MJ, Dautzenberg PL, van Bergen FS, ter Bruggen JP, Olde Rikkert MG. Pilot study of a three-step diagnostic pathway for young and old patients with Parkinson’s disease dementia: screen, test and then diagnose. Int J Geriatr Psychiatry 2009. Cnossen TT, Smit W, Konings CJ, Kooman JP, Leunissen KM, Krediet RT. Quantification of free water transport during the peritoneal equilibration test. Perit Dial Int. 2009 Sep-Oct; 29(5):523-7. Krediet RT, Coester AM, Kolesnyk I, de Graaff M, Zweers MM, Smit W, Struijk DG. Karl d. Nolph state of the art lecture: feasible and future options for salvation of the peritoneal membrane. Perit Dial Int. 2009 Feb;29 Suppl 2:S195-7. Cnossen T, Beerenhout C, Smit W, Konings C, Kooman J, Leunissen K, Krediet RT. Influence of the preceding dwell time on the peritoneal equilibration test with 3.86% glucose solution in automated peritoneal dialysis. Perit Dial Int. 2010 Jan-Feb;30(1):95-8. Toonen F, Smilde T. A retroperitoneal mass with elevated alpha-I-

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fetoprotein: not always a testicular carcinoma. The Netherlands Journal of Medicine; 2010; 68: 33-34. Case report. Van Poppel PC, Stehouwer CD, Beutler JJ, Korst MB, Beerlage HP, Hoogeveen EK. Hyperchloremische metabole acidose bij een patiënt met een brickerlis Ned Tijdschr Geneeskd. 2009;153:B317. Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, Braam B, Huysmans FT, Schultze Kool LJ, Rutten MJ, Doorenbos CJ, Aarts JC, Rabelink TJ, Plouin PF, Raynaud A, van Montfrans GA, Reekers JA, van den Meiracker AH, Pattynama PM, van de Ven PJ, Vroegindeweij D, Kroon AA, de Haan MW, Postma CT, Beutler JJ. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med. 2009 Jun 16;150(12):840-8, W150-1. Kampschreur LM, Wegdam-Blans MC, Thijsen SF, Groot CA, Schneeberger PM, Hollander AA, Schijen JH, Arents NL, Oosterheert JJ, Wever PC. Acute Q fever related in-hospital mortality in the Netherlands. Neth J Med. Dec 2010 Velden WJ, Herbers AH, Feuth T, Schaap NP, Donnelly JP, Blijlevens NM. Intestinal damage determines the inflammatory response and early complications in patients receiving conditioning for a stem cell transplantation. PloS one 2010. Vol 5, 12: 1-8. Ennink TA, Hamilton CJ, Kemperman FA. PICO Bello – Heeft behandeling van subklinische hypothyreoïdie bij zwangere vrouwen een positief effect op de neurologische ontwikkeling van het kind. Ned Tijdschr Obstr Gyn 2010 Feb; 121(2): blz 23-25


“Dit is een ervaring, die ik niet had willen missen”

Linda Kampschreur volgt de opleiding tot internist aan het Universitair Medisch Centrum in Utrecht. Ze is bijzonder geïnteresseerd in de besmettelijke ziekte Q-koorts en verdiept zich bij het Jeroen Bosch Ziekenhuis in de praktijk. Ze is jong, ambitieus en bevlogen in haar vak. Wat drijft haar? “De eerste drie jaar van mijn opleiding volgde ik in het Jeroen Bosch ziekenhuis. Vorig jaar sprak ik een microbioloog van dit ziekenhuis, die mij vroeg of ik geïnteresseerd was in onderzoek naar Q-koorts”, aldus Kampschreur. “Deze kans liet ik natuurlijk niet voorbij gaan. Ik mocht ook de Q-koorts poli in het JBZ komen versterken: ik werk nu één dag per week op de poli en dat combineer ik met mijn onderzoek.”

interview linda kampschreur

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Ziektebeeld Kampschreur: “Je hebt twee vormen: acute en chronische Q koorts. Ruim de helft van de mensen die besmet zijn, wordt overigens helemaal niet ziek. Zij die wél ziek worden, krijgen er binnen een paar weken na besmetting last van. Er is dan vaak sprake van koorts, koude rillingen, spier- en hoofdpijn. Dit gaat meestal weer gewoon over. Bij een kleine groep patiënten ontstaat echter chronische Q koorts, zelfs tot tien jaar na de eerste infectie. Vaak uit zich dit in ontsteking van de hartkleppen, grote vaten of hart- of vaatprothesen. De kans om chronische Q-koorts te krijgen is groter voor zwangere vrouwen, patiënten met hartklepafwijkingen, aneurysma’s of vaatprothesen. Zonder behandeling kan het tot ernstige complicaties lijden. Mensen met een chronische besmetting krijgen vaak langdurig antibiotica toegediend en dat valt hen zwaar. Dit zijn allemaal redenen om hier onderzoek naar te doen.” Uniek Binnen haar onderzoek heeft ze een aantal werkzaamheden. Kampschreur: “De diagnostiek was altijd lastig en we maakten gebruik van onderzoeksresultaten uit het buitenland. Maar met de uitbraak in Nederland hadden we ineens zelf een unieke onderzoekspopulatie. Daar wilden we gebruik van maken. Zo stel ik een database op voor alle patiënten met chronische Q koorts in Nederland. Ik wil weten: wat zijn dat voor mensen? Wat voor achtergrond en historie hebben zij? Dat geeft ons nog meer inzicht in de oorzaak van de chronische infectie.” Preventief “Ook schreven we mensen aan die in het verleden een hartklepprothese of hartklepoperatie hadden. Want zij hebben verhoogde kans om chronische Q-koorts op te lopen. Wij wilden hen preventief screenen om er zeker van te zijn dat deze ziekte geen kans van slagen zou hebben. Want als de Q-koortsbacterie zich bij die patiënten op de hartklep nestelt, is dat heel gevaarlijk.” Kampschreur zit in een landelijke werkgroep. “Hier stellen internisten, microbiologen, cardiologen en vaatchirurgen richtlijnen op voor chronische Q-koorts patiënten. Dit met als doel om onze eigen diagnoses en behandelingen scherper te maken.” Onder de loep Kampschreur: “Met onderzoek kunnen we de wetenschap kritisch onder de loep nemen. Ook bij het analyseren van statistieken is het de kunst om juist op een andere manier naar gegevens te kijken. Want soms zijn uitkomsten van een onderzoek niet zo hard als ze op papier lijken.” Lachend: “Ook op persoonlijk vlak leer ik veel. Zo doe ik nu meer aan timemanagement en leer ik om goed te communiceren met iedereen die bij het onderzoek betrokken is. Dit is een ervaring, die ik niet had willen missen.”

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9

KINDERGENEESKUNDE Wetenschappelijke publicaties Schatorjé E, Hoekstra JH. Transient hypertransaminasemia in paediatric patients with crohn disease undergoing initial treatment with enteral nutrition. J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):336-40. PMID: 20601906

DA, Bocca G, Mieke Houdijk EC, Hokken-Koelega AC. Bone mineral density and effects of growth hormone treatment in prepubertal children with Prader-Willi syndrome: a randomized controlled trial. J Clin Endocrinol Metab. 2009 Oct;94(10):3763-71. PMID: 19622627

Hoekstra JH, van der Weij AM, Groot-Loonen J, Hoogerbrugge P, Kooy Y, Koning F. Succesful treatment of celiac disease by allogeneic haematopoietic stem cell transplantation. J Pediatr Gastroenterol Nutr 2010;51:793-4 PMID: 20890214

Vink EE, van Coeverden SC, van Mil EG, Felius BA, van Leerdam FJ, Delemarre-van de Waal HA. Changes and tracking of fat mass in pubertal girls. Obesity (Silver Spring). 2010 Jun;18(6):1247-51. PMID: 19875991

de Lind van Wijngaarden RF, Siemensma EP, Festen DA, Otten BJ, van Mil EG, Rotteveel J, Odink RJ, Bindels-de Heus GC, van Leeuwen M, Haring DA, Bocca G, Houdijk EC, Hoorweg-Nijman JJ, Vreuls RC, Jira PE, van Trotsenburg AS, Bakker B, Schroor EJ, Pilon JW, Wit JM, Drop SL, Hokken-Koelega AC. Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome. J Clin Endocrinol Metab. 2009 Nov;94(11):4205-15 PMID: 19837938 de Lind van Wijngaarden RF, Festen DA, Otten BJ, van Mil EG, Rotteveel J, Odink RJ, van Leeuwen M, Haring

kindergeneeskunde

Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009 May;156(2):189-93. Epub 2009 Jan 22. Review. PMID: 19250275. Trefwoorden: Downsyndroom, immuundeficiëntie.

Verstegen RH, Kusters MA, Gemen EF, de Vries E. Down syndrome B-lymphocyte subpopulations, intrinsic defect or decreased T-lymphocyte help. Pediatr Res. 2010 May;67(5):563-9. PMID: 20098344. Trefwoorden: Downsyndroom, immuundeficiëntie.

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Kusters MA, Gemen EF, Verstegen RH, Wever PC, de Vries E. Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T lymphocytes. Pediatr Res. 2010 May;67(5):557-62. PMID: 20098345. Trefwoorden: Downsyndroom, immuundeficiëntie

Van Beek E, Binkhorst M, de Hoog M, de Groot P, van Dijk A, Schokking M, Hopman M. Exercise performance and activity level in children with transposition of the great arteries treated by the arterial switch operation. Am J Cardiol 2010; 105: 398-403. PMID: 20102956 Trefwoorden: inspanningstolerantie, congenitale hart

Hartley JL, Zachos NC, Dawood B, Donowitz M, Forman J, Pollitt RJ, Morgan NV, Tee L, Gissen P, Kahr WHA, Knisely AS, Watson S, Chitayat D, Booth IW, Protheroe S, Murphy S, de Vries E, Kelly DA, Maher ER. Mutations in TTC37 Cause Trichohepatoenteric Syndrome (Phenotypic Diarrhoea of Infancy). Gastroenterology. 2010 Jun;138(7):2388-98, 2398.e1-2. PMID: 20176027.

De Groot PC, Thijssen D, Binkhorst M, Green DJ, Schokking M, Hopman MT. Vascular function in children with repaired tetralogy of Fallot. Am J Cardiol. 2010 Sep 15;106(6):851-5. PMID: 20816127

Trefwoorden: Fenotypische diarree, immuundeficiëntie.

Trefwoorden: vaatfunctie, congenitale hartafwijkingen

Deniz G, Chapel H, Barlan I, de Vries E, Jaraquemada D. Women advancing science. Eur J Immunol. 2010 Mar;40(3):589-92. PMID: 20201011.

Mattheij M, van der Weij AM. A girl with recurrent swelling of the parotis region. Ned Tijdschr Geneesk. 2009;153-A188. PMID: 19930740

afwijkingen

Trefwoorden: Emancipatie, wetenschap.

Poodt AE, Driessen GJ, de Klein A, van Dongen J J, van der Burg M, de Vries E. TACI mutations and disease susceptibility in patients with common variable immunodeficiency. Clin Exp Immunol. 2009 Apr;156(1):35-9. PMID: 19210517 Binkhorst M, de Leeuw N, Otten BJ. A healthy, female chimera with 46,XX/46,XY karyotype. J Pediatr Endocrinol Metab 2009; 22: 97-102. PMID: 19344081

Munster JM, Leenders AC, van der Hoek W, Schneeberger PM, Rietveld A, Riphagen-Dalhuisen J, Stolk RP, Hamilton CJ, de Vries E, Meekelenkamp J, Lo-Ten-Foe JR, Timmer A, De Jong-van den Berg LT, Aarnoudse JG, Hak E. Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial. BMC Womens Health. 2010 Nov 1;10(1):32. PMID: 21040534.

Trefwoorden: chimeer, intersexualiteit

Boeken

Binkhorst M, de Gier RP. A large extra-abdominal prevesical pseudo-cyst in a newborn with posterior urethral valves. J Pediatr Urol 2010; 6: 91-93. PMID: 19477688

van Mil EG. Neonatale Hypoglycemiëen. C. Noordam. Uit: Werkboek Kinderendocrinologie. Serie: Werkboeken kindergeneeskunde. Eindredactie. C.M.F. Kneepkens. VU Uitgeverij. 2010 Amsterdam.

Trefwoorden: urethrakleppen, blaasruptuur

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Kuijpers TW, Prakken AB, de Vries E. Het immuunsysteem, afweerstoornissen en allergie. In: van den Brande JVL, Derksen-Lubsen G, Heymans HSA, Kollée LAA (Eds.). Leerboek kindergeneeskunde. Een interactieve benadering in woord en beeld. De Tijdstroom Uitgeverij, Utrecht, 2010. Met dvd-rom. ISBN 978-9-058-98079-3.

Abstracts, voordrachten en posters Hoekstra JH, van der Weij A, Groot-Loonen J, Hoogerbrugge P, Kooy Y, Koning F. Poster: Celiac disease cured by allogenic hematopoietic stem cell transplantation. Proceedings13th International Coeliac Disease Symposium, Amsterdam, 2009 Schatorjé E, Hoekstra JH. Poster: Transient hypertransaminasemia in pediatric patients with Crohn’s disease undergoing initial treatment with enteral feeding. Proceedings PIBD, Paris, 2009, J of Crohn’s and Colitis 2009,3:S7 De Bie CI, Hummel TZ, Kinderman A, Kokke FT, Damen GM, Kneepkens CMF, van Rheenen PF, Schweitzer JJ, Hoekstra JH, Norbruis OF, Tjon A Ten WE, Vreugdenhil AC, Deckers J, Gijsbers, de Ridder L. Escher JC. Poster: Long-term efficacy of infliximab treatment in pediatric Crohn’s disease in The Netherlands. Proceedings AGA, New Orleans, 2010 Hoekstra JH. Complicaties na rotavirusinfecties. Periodieke conferentie, Nijmegen, 26 januari 2009. Hoekstra JH. Evidence Based behandeling van acute diarree. EPGS, Amsterdam, 5 februari 2009. Hoekstra JH. ESPGHAN/ESPID EBM Guidelines for the treatment of

kindergeneeskunde

acute gastro-enteritis. Karolinka seminars, Stockholm, 25 maart 2009. Hoekstra JH. Een nieuwe manier om te selecteren voor de opleiding tot kinderarts. PRG, Leuven, 26 september 2009. Hoekstra JH. Complementary feeding. Eastern ESPGHAN Summer School, Budva, 9 september 2010. Hoekstra JH. Enteral feeding. Eastern ESPGHAN Summer School, Budva, 10 september 2010. Mattheij MA, van Mil EG. Obesity in children: what Dutch pediatricians see and do. Obesity Facts, 2 (suppl 1): 2009 van Mil EG. Management of childhood obesity: lessons from a business case. Obesity Facts, 2 (suppl 1): 2009 Schatorjé E, Gemen EF, Driessen GA, Leuvenink J, van der Burg M, de Vries E. Poster: Age-matched reference values for lymphocyte subpopulations show limitations of current EUROclass CVID classification in children.

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European Society for Immunodeficiencies, Istanbul, 2010. Schatorjé E, de Vries E. Voordracht: Normaalwaarden lymfocytensubsets in relatie tot CVID classificatie bij kinderen. Werkgroep Immuundeficiënties, Utrecht, 2010. Walker JC, Smolders MA, Gemen EF, Antonius TA, de Vries E. Poster: Ontwikkeling van lymfocytensubpopulaties bij prematuren. Nederlandse Vereninging voor Kindergeneeskunde, Veldhoven, 2009. Kusters MA, Jol-van der Zijde CM, Van Tol MJ, Bolz WE, Bok LA, Visser M, de Vries E. Poster: Serum antibody response to tetanus toxoid in children with Down syndrome. European Society for Paediatric Infectious Diseases, Brussel, 2009.

Kusters MA, de Vries E. Voordracht: Het afweersysteem bij kinderen met Down syndroom. Werkgroep Immuundeficienties, Utrecht, 2009. Kusters MA, de Vries E. Voordracht: Vaccinatieresponsen bij kinderen met Down syndroom. Werkgroep Immuundeficienties, Utrecht, 2010. Driessen GJ, van Zelm MC, van Hagen PM, Hartwig NG, Trip M, Warris A, de Vries E, Barendregt BH, Pico I, van Dongen JJ, van der Burg M. Poster: Patients with idiopathic hypogammaglobulinemia can be divided in B-cell phenotypes with different proliferation and somatic hypermutation defects. European Society for Immunodeficiencies, Istanbul, 2010.

Mattheij MA, de Vries E. Voordracht: Een vermoeden van antibiotica-allergie bij kinderen blijkt bij provocatie vaak onterecht. Nederlandse Vereniging voor Kindergeneeskunde, Veldhoven, 2009.

Van Beek E, Binkhorst M, de Hoog M, de Groot P, van Dijk A, Schokking M, Hopman M. Exercise performance and activity level in children with transposition of the great arteries treated by the arterial switch operation. Congres kindercardiologie, Weimar, Duitsland, oktober 2009.

Kusters MA, Jol-van der Zijde CM, van Tol MJ, Bolz WE, Bok LA, Visser M, de Vries E. Poster: Children with Down syndrome show decreased antibody response to tetanus toxoid. European Congress of Immunology, Berlijn, 2009.

Publicaties (niet pubmed)

Kusters MA, de Vries E. Voordracht: T-lymfocyten bij kinderen met Down syndroom (DS). Jonge Onderzoekersdag Nederlandse Vereniging voor Kindergeneeskunde, Veldhoven, 2009. Verstegen RH, de Vries E. Voordracht: B-lymfocyten bij het syndroom van Down: intrinsiek defect of gestoorde hulp van T-lymfocyten? Jonge Onderzoekersdag Nederlandse Vereniging voor Kindergeneeskunde, Veldhoven, 2009.

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Langens FN, van Binsbergen JJ, van Mil EG, Seidell JC. Obesitas en een verhoogd cardiovasculair risico: de aanpak begint al op jeugdige leeftijd! Hartbulletin december 2009 van Mil EG. Overgewicht bij een kind is eigenlijk niet meer dan een signaal. Health Management Forum. Maart 2009 van den Akker EL, van Mil EG. Obesitas: Gen Diagnostiek en Geen Diagnostiek. Praktische Pediatrie. April 2009


Vink EE, van Coeverden SC, van Mil EG, Felius BA, van Leerdam FJ, Delemarre-van de Waal HA. Changes and tracking of fat mass in pubertal girls. Obesity 2010 Jun;18(6):1247-51 Renders CM, Bulk-Bunschoten AM, van Mil EG. De richtlijn ‘Diagnostiek en behandeling van obesitas bij kinderen’. Praktische Pediatrie 2010 Juni. Jaargang 4, nr2: 94-100 van Mil EG, van den Akker EL. Het metabool syndroom bij overgewicht en obesitas. Praktische Pediatrie 2010 Juni. Jaargang 4, nr2: 102-106 van Heurn LW, Vreugdenhil A, van Mil EG. Een extreem dik kind: is operatieve behandeling wenselijk? Praktische Pediatrie 2010 Juni. Jaargang 4, nr2: 107-110 van Mil EG. Editorial: Samen sterk in de strijd tegen overgewicht. Tijdschr Kindergeneeskund 2010; nr 3; 78: 98-99 Renders CM, Bulk-Bunschoten AM, van Mil EG. De CBO-richtlijn Diagnostiek en behandeling van obesitas bij volwassenen en kinderen’ – wat betekent dit voor de kindergeneeskunde? Tijdschr Kindergeneeskund 2010; nr 3; 78: 100-106 van Heurn LW, van Mil EG, Greve JW, Delemarre-van de Waal HA. De chirurgische behandeling van morbide obesitas bij kinderen. Tijdschr Kindergeneeskund 2010; nr 3; 78: 114-118 de Vries E, Driessen GJ. Primary immunodeficiencies in children: a diagnostic challenge. Eur J Pediatr, in press. Trefwoorden: Diagnostiek, immuundeficiëntie.

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Bruggen bouwen met Bossche bollen

Het Jeroen Bosch Ziekenhuis (JBZ) doet al enige tijd wetenschappelijk onderzoek naar afwijkingen in het afweersysteem bij Downsyndroom. Want bij deze patiënten komen vaker infecties voor. Maaike Kusters doet er onderzoek naar en brengt verslag uit. “Ik studeerde geneeskunde en kwam via een wetenschappelijke stage in het JBZ terecht. Doordat ik de afgelopen jaren als ANIOS (arts-assistent niet in opleiding tot specialist) bij de kindergeneeskunde in ’s-Hertogenbosch werkte, kon ik naast mijn werkzaamheden als arts ook doorgaan met het onderzoek. Inmiddels ben ik in opleiding tot kinderarts in het Academisch Ziekenhuis Maastricht. Ik verwacht in 2012 via de ‘Bossche’ constructie in Leiden te Promoveren.” Last van infecties Kusters vertelt over de achtergronden van haar specialisme. “Het afweersysteem van kinderen met Downsyndroom werkt minder goed. Daardoor hebben ze vaker last van infecties. Ook lijkt het erop dat kinderen met Downsyndroom minder goed reageren op sommige vaccinaties.” Daarom wil het JBZ er

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graag onderzoek naar doen. “Afgelopen jaren deden we al veel onderzoek op dit gebied. Zo keken we naar de verschillende afweercellen en afweerstoffen. Veel afweercellen komen minder voor, terwijl de afweerstoffen soms juist verhoogd zijn in vergelijking met kinderen zonder Downsyndroom.” Onderzoek “Daarom zijn we verder gaan kijken hoe deze afweercellen en de afweerstoffen hun werk doen. De reactie op vaccinatie en de productie van afweerstoffen hiertegen geeft een beter inzicht in hoe het afweersysteem werkt”, vult Kusters verder aan. “We onderzoeken bijvoorbeeld wat de reactie is van het afweersysteem van deze kinderen op een vaccinatie tegen pneumococcen. Dit is een bacterie die vaak luchtweg-infecties zoals longontsteking en middenooronsteking veroorzaakt, iets wat bij kinderen met Downsyndroom juist veel voorkomt. Maar ook kijken we naar vaccinaties tegen Mexicaanse griep, tetanus en meningococcen.” Onderzoek doen geen kinderspel Een onderzoek is niet van vandaag op morgen afgerond. Kusters: “Het mag duidelijk zijn dat een onderzoekstraject zorgvuldig en met veel voorbereiding gebeurt. Je mag bijvoorbeeld nooit zomaar een medisch-wetenschappelijk onderzoek starten. Want eerst moet een erkende medisch-ethische commissie beoordelen of het onderzoek wel verantwoord is en voldoet aan alle eisen. Immers, je doet wel onderzoek met kinderen!” Krachten bundelen “Daarbij is een aantal dingen essentieel bij het doen van onderzoek”, aldus Kusters. “Het is belangrijk dat je goede contacten legt met externe partners. Want zo kun je gebruik maken van elkaars krachten.” Kusters licht dit toe aan de hand van een voorbeeld. “Het JBZ is een uitstekend perifeer ziekenhuis, maar beschikt niet altijd over alle apparatuur die vaak wel in de academische centra aanwezig is. Maar het JBZ heeft wel over een grote patiëntenpopulatie van kinderen met Downsyndroom die regelmatig in het ziekenhuis komen voor policontroles en zo gemakkelijk mee kunnen doen aan onderzoek. Daarom werken we samen met diverse centra om de krachten te bundelen. Vaak gaat dit gepaard met het uitwisselen van expertise of het publiceren van een gezamenlijk wetenschappelijk artikel.” Ze knipoogt: “Maar ook met het uitwisselen van Bossche bollen. Want daarmee zijn al heel wat bruggen gebouwd!” Wilt u meer weten over dit onderzoek? Neem gerust een kijkje op www.linkedin.com en type “Maaike Kusters” in bij het zoekscherm.

interview Maaike kusters

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KLINISCHE CHEMIE & HEMATOLOGIE Wetenschappelijke publicaties Verstegen RH, Kusters MA, Gemen EF, de Vries E. Down syndrome B-lymphocyte subpopulations, intrinsic defect or decreased T-lymphocyte help. Pediatr. Res. 2010 May;67(5):563-9. PMID: 20098344 Kusters MA, Gemen EF, Verstegen RH, Wever PC, de Vries E Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T-lymphocytes. Pediatr Res. 2010 May;67(5):557-62. PMID: 20098345 Schmeits PC, Péquériaux NC, van Geest-Daalderop JH, Ouwehand ME, Coremans AM, Hermans MH, Conemans JM. Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin. Neth J Med. 2009 Feb;67(2):76-8. PMID: 19299851 van Geest-Daalderop JH, Péquériaux NC, van den Besselaar AM. Variability of INR in patients on stable long-term treatment with phenprocoumon and acenocoumarol and implications for analytical quality requirements

klinische chemie & hematologie

Thromb Haemost. 2009 Sep;102(3):588-92. PMID: 19718481 Trefwoorden: Vitamin K antagonist, international normalised ratio, biological variation, analytical performance goal

de Jager CP, de Wit NC, Weers-Pothoff G, van der Poll T, Wever PC. Procalcitonin kinetics in Legionella pneumophila pneumonia. Clin Microbiol Infect. 2009 Nov;15(11):1020-5. PMID: 19438643 De Wit NC, de Jager CP, Meekelenkamp JC, Schoorl M, van Gageldonk-Lafeber AB, Leenders AC, Kusters R, Wever PC. Markers of infection in inpatients and outpatients with acute Q-fever. Clin Chem Lab Med. 2009;47(11):1407-9. PMID: 19778289 Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome; a review. Clin Exp Immunol. 2009 May;156(2):189-93. PMID: 19250275

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Meijer RP, Gemen EF, van Onna IE, vd Linden JC, Beerlage HP, Kusters GC. The value of an artificial neural network in the decision-making for prostate biopsies. World J Urol. 2009 Jun 28 Volume 27, Issue 5 (2009), Page 593. PMID: 19562346 Hermans MH, Poodt J, van Geest-Daalderop JH, Péquériaux NC, Conemans JM. Resistance to coumarin derivatives due to mutated vitamin-K enzyme. Ned Tijdschr voor Geneeskd. 2009:153:A691 PMID: 19857286 De Waard H, van ’t Sant P. Use of serum myoglobin assays for urine myoglobin measurements can cause false-negative results. Clin. Chem. 2009 Jun;55(6):1240-1. PMID: 19342504 Schmeits PC, Hermans MH, van Geest-Daalderop JH, Poodt J, de Sauvage Nolting PR, Conemans JM. VKORC1 mutations in patients with partial resistance to phenprocoumon. Br J Haematol. 2010 Mar;148(6):955-7. PMID: 19961479

Van Geest-Daalderop JH, Kraaijenhagen RJ, Van Der Meer FJ, Van Den Besselaar AM. Intraindividual variation of the International Normalized Ratio in patients monitored with a recombinant human thromboplastin. J Thromb Haemost. 2010 Jul;8(7):1641-2. PMID: 20403089 Van Geest-Daalderop JH, Hutten BA, Péquériaux NC, Levi M, Sturk A. Improvement in the regulation of the vitamin K antagonist acenocoumarol after a standard initial dose regimen: prospective validation of a prescription model. J Thromb Thrombolysis. 2009 Feb;27(2):207-14. PMID: 18270659 De Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 2010;14(5):R192. PMID: 21034463

Boeken de Wit NC Klinische Chemie en Hematologie voor Analisten. Deel 2, Hoofdstuk 17: “Bloedgassen” Lesboek “Klinische Chemie en Hematologie voor Analisten”. Editors: E. ten Boekel en B.A. de Boer. Heron reeks Februari 2010. ISBN 9789077423738

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De Waard H, van ’t Sant P. Klinische Chemie deel 1. Hoofdstuk 3. De chemie-analyser en inleiding tot de fotometrie. Uitgever: Syntax media, Arnhem, 33-50. Heron reeks Maart 2009. ISBN 9789077423684


Abstracts, voordrachten en posters Gemen EF Voordracht: The value of an artificial neural network in the decision-making for prostate biopsies. Wetenschapsdag Jeroen Bosch Ziekenhuis,’sHertogenbosch, 4 Februari 2010. (3e prijs behaald). Hoedemakers RM, Martens HA, Pruijt JF. Poster: Efficiënt screening algoritme voor detectie van monoklonale gammopathie. NVKC congres, Veldhoven, 22 april 2010 t/m 23 april 2010. Hoedemakers RM, Martens HA, Pruijt JF. Abstract: Efficiënt screening algoritme voor detectie van monoklonale gammopathie. Nederlands Tijdschrift Klinische Chemie en Laboratoriumgeneeskunde 2010; 35:107-108. de Waard H, Gemen EF, Leuvenink J, Péquériaux NC Poster: Diagnostiek ijzergebrek, RET-He of toch maar klassiek? Een systematische vergelijking met de ijzervoorraad in beenmerg. NVKC congres, Veldhoven, 22 april 2010 t/m 23 april 2010. Leuvenink J, Gerven MP, Martens HA Poster: IJzerdeficiëntie en Hb-pathie vaststellen op basis van volbloedparameters. NVKC congres, Veldhoven, 22 april 2010 t/m 23 april 2010. van Hulstein J, de Waard H, van Gool MJ, Vanderloo RA, Kusters GC, van ‘t Sant P Poster : Validatie Dimension Vista 1500 (Siemens Healthcare Diagnostics). NVKC congres, Veldhoven, 22 april 2010 t/m 23 april 2010. Schatorjé E, Gemen EF, Driessen GA, Leuvenink J, van der Burg M, de Vries E Poster: Age-matched reference values for lymphocyte


subpopulations show limitations of current EUROClass CVID classification in children. ESID, Istanbul, Turkije, 6 oktober 2010 t/m 9 oktober 2010. Kariman MA, Gemen EF, Péquériaux NC Poster: Verlenging van het tijdsinterval tussen bloedafname en plasmabereiding naar 6 uur is zonder consequentie voor routine stollingsonderzoek. NVKC congres, Veldhoven, 22 april 2010 t/m 23 april 2010. Gemen EF, Kusters MA. Kunst poster: thema “ Immunologie/primaire afweerziekten”, titel: Mijkes world ESID, Istanbul, Turkije, 6 oktober 2010 t/m 9 oktober 2010. (ESID Junior Best PID&ART Award 2010 behaald) de Waard H, Gemen EF, Leuvenink J, Péquériaux NC Poster: Iron deficiency, a systemic comparison of red blood cell parameters, ferritin and iron-stores in the bonemarrow. First European Joint congress of EFCC and UEMS, Lissabon, Portugal, 13 oktober 2010 t/m 16 oktober 2010. (1e prijs behaald) van ’t Sant P, de Waard H. Voordracht: Traject naar geautomatiseerd laboratorium 2011/2012. Regio overleg klinisch chemici Oost Brabant, 2 april 2009. Hoedemakers RM Voordracht: Efficiente workflow M-proteinen onderzoek Sebia gebruikersdag, Februari 2009. Péquériaux NCV, van Litsenburg EHAA, Kooyman PJ, Ligthart, M de Haas PC. Poster: CASUS: Complexe antistoffen binnen het Kell systeem bij noodzaak tot onderbeenamputatie. NVB symposium, Ede, 13 mei 2009.

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van Litsenburg EHAA, Péquériaux NCV. Poster: Zeer ernstige auto-immuun hemolytische anaemie; Transfusie met rug tegen de muur. NVB symposium, Ede, 13 mei 2009. van Litsenburg EHAA, Péquériaux NCV. Voordracht: Zeer ernstige auto-immuun hemolytische anaemie; Transfusie met rug tegen de muur. NVB symposium, Ede, 13 mei 2009. Walker JC, Smolders MAJC, Gemen EFA, de Vries E. Poster: Ontwikkeling van lymfocytensubpopulaties bij prematuren. NVK Veldhoven, 4 t/m 6 nov 2009. Péquériaux NC. Voordracht: DVT Diep veneuze trombose. Huisartsen duodagen microbiologie en klinische chemie. 27 mei en 2 juni 2009. de Wit NC, Oosting JD, Hoffmann JJ, Krockenberger L, van Dun M. Poster: Novel method for measuring reticulated platelets using the Abbott Cell Dyn Sapphire. ISLH Symposium, Las Vegas, USA, Mei 2009.

de Wit NC, Oosting JD, Hoffmann JJ, Krockenberger L, van Dun M. Poster: Comparative Evaluation of the Abbott CELL-DYN Sapphire Reticulated Platelets fraction and the Sysmex XE-2100 IPF. ISLH Symposium, Las Vegas, USA, Mei 2009. de Wit NC. Voordracht: Reticulated platelets. ISLH Symposium, Las Vegas, USA, Mei 2009. Poodt J, Schmeits PC, Van Geest-Daalderop JH, Conemans JM, Hermans MH. Poster: Patients with partial resistance to acenocoumarol and phenprocoumon; screening the VKORC1 gene. European Meeting on Molecular Diagnostics, Scheveningen, 22/23-10-2009. Vissers E, de Jager CP, Kusters R, van Gageldonk-Lafeber AB, Wever PC. Poster: Hypophosphatemia and prolonged length of hospital stay in seronegative PCR positive patients with early acute Q-fever. Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, 18-19 november 2010.

Publicaties (niet pubmed) Hoedemakers RM, Martens HA, Pruijt JF. Efficiënt screeningalgoritme voor detectie van monoklonale gammopathie. Ned Tijdschr Klin Chem Labgeneesk 2010; 35: 182-183. Gijsbrechts C Nederland komt vitamine D3 tekort. Folia Orthica, jaargang 2010, nr 1; mei 2010 pag 26-27. van ‘t Sant P, de Waard H Reflecterend testen: een toegevoegde

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waarde bij laboratoriumdiagnostiek, van reflexen naar reflectie. Labcontact 2010, nr 32. Wetzer PM, Péquériaux NCV. Plasmatransfusies, doen wij het goed? Tijdschrift voor bloedtransfusie, VOL.2 NR.3 – 2009. Trefwoorden: CBO-richtlijn Bloedtransfusie 2004, FFP.

van Lieshout AWT, Kampschreur LM, de Jongh J, Sinnige HAM. Anemie met een Chinees tintje.


NTVH, Vol. 6 Nr. 5; 2009. Trefwoorden: anemie, chelatietherapie Conemans J, Poodt J, Schmeits P, Péquériaux N, van Geest A, Hermans M. Een nieuwe VKORC1-mutatie in een patiënt met fenprocoumonresistentie. Cura: April 2009. de Wit NC, Oosting JD. Evaluatie van de aangepaste 4-5-6-flexinorm in Ziekenhuis. Bernhoven. Nederlands Tijdschrift voor Bloedtransfusie 2009, 2,(1) 10-14. de Wit NC, Baadenhuijsen H, Weykamp CW, van ’t Sant P. Geen goede commuteerbaarheid van monsters in de SKML Combi Algemene Chemie enquete voor de ASAT-bepaling. Ned Tijdschr Klin Chem Labgeneesk 2009; 34: 162-164. Gemen EF, de Wit NC, van Gerven MP, de Jongh-Leuvenink J. The Sysmex SP1000i for Automated Bone Marrow Slide Smear Staining. LABMEDICINE December 2009 vol 40 no 12 pp 719-723. Conemans J, Péquériaux N, de Boer M, Eppenga W. Wat moet de huisarts weten over orale anticoagulantia en de trombosedienst? Labcontact 2009, oktober, nr 30.


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KLINISCHE FYSICA Abstracts, voordrachten en posters Renders AH, Claessens RA. Voordracht: Bouw, kwaliteitscontrole en toepassing van een generator voor Rb-82. XXIVe NVKF-conferentie Woudschoten Nederland, 15 en 16 mei 2009. Renders AH. Quality assurance in nuclear medicine. Gastcollege aan de Universiteit Twente in de cyclus ‘Medical Technology’ 11 maart 2009 en 31 maart 2010.

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KNO-HEELKUNDE Abstracts, voordrachten en posters Balter SG Gastspreker op Tinnitus Informatie-avond (georganiseerd door de NVVS) JBZ lokatie Carolus ziekenhuis, 9 maart 2010

Op de Coul B, Presentatie “Innovaties binnen KNO/ KNOstraten-boek” Duodagen Huisartsen Vlissingen, 2-3 december 2010.

Op de Coul B, Presentatie “Hooikoorts bestaat niet meer.” Huisartsen en Apothekers Vught, 30 juni 2010.

De Visscher AV Het KNO-stratenboek 1e editie Voordracht Bossche samenscholingsdagen, Vlissingen, 25 en 26 november 2010.

Publicaties (niet pubmed) Rutten GJ, Op de Coul B, Verschoor N. Cervicale hyperostosis als behandelbare oorzaak voor dysfagie. Nederlands Tijdschrift voor Keel- Neus en Oorheelkunde, 2009;15(1):29-31.

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LONGZIEKTEN Wetenschappelijke publicaties Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. PMID: 20570559 Krzakowski M, Ramlau R, Jassem J, Szczesna A, Zatloukal P, Von Pawel J, Sun X, Bennouna J, Santoro A, Biesma B, Delgado FM, Salhi Y, Vaissiere N, Hansen O, Tan EH, Quoix E, Garrido P, Douillard JY. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol. 2010 May 1;28(13):2167-73. PMID: 20351334 Scagliotti GV, Germonpré P, Bosquée L, Vansteenkiste J, Gervais R, Planchard D, Reck M, De Marinis F, Lee JS, Park K, Biesma B, Gans S, Ramlau R, Szczesna A, Makhson A, Manikhas G, Morgan B, Zhu Y, Chan KC, von Pawel J.

longziekten

A randomized phase II study of bortezomib and pemetrexed, in combination or alone, in patients with previously treated advanced non-small-cell lung cancer. Lung Cancer. 2010 Jun;68(3):420-6. PMID: 19692142 Veen EJ, Janssen-Heijnen ML, Ritchie ED, Biesma B, van den Bogart MP, Bolhuis RJ. Pneumonectomy for bronchogenic carcinoma: analysis of factors predicting short- and long-term outcome. Interact Cardiovasc Thorac Surg. 2009 Aug;9(2):260-4. PMID: 19443491 Smit EF, Burgers SA, Biesma B, Smit HJ, Eppinga P, Dingemans AM, Joerger M, Schellens JH, Vincent A, van Zandwijk N, Groen HJ. Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer. J Clin Oncol. 2009 Apr 20;27(12):2038-45. PMID: 19307503 Goss G, Ferry D, Wierzbicki R, Laurie SA, Thompson J, Biesma B, Hirsch FR, Varella-Garcia M, Duffield E, Ataman OU, Zarenda M, Armour AA.

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Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status. J Clin Oncol. 2009 May 1;27(13):2253-60. PMID: 19289623

Pompen M, Gok M, Novák A, van Wuijtswinkel R, Biesma B, Schramel F, Stigt J, Smit H, Postmus P. Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands. Lung Cancer. 2009 Apr;64(1):110-6. PMID: 18805601

Boeken Schreurs AJ. Corticosteroïden. In: COPD, Dekhuijzen,P.N.R. (ed),van Zuiden Comm. B.V., 2009.

Abstracts, voordrachten en posters Gatzemeier U, Eisen T, Santoro A, Paz-Ares L, Bennouna J, Liao M, Strauss UP, Montegriffo E, Ong TJ, Biesma B. Voordracht: Sorafenib (S) + Gemcitabine/Cisplatin (GC) vs GC alone in the First-line treatment of advanced non-small cell lung cancer (NSCLC): phase III NSCLC research experience utilizing Sorafenib (NExUS) trial. ESMO meeting, 8-12 October 2010, Milan. Groen HJM, Hochstenbag MMH, van Putten JWG, Vincent A, Dalesio O, Biesma B, Smit JM, Termeer A, van den Borne BEEM, Schramel FMNH. Abstract: A randomized placebo-controlled phase III study of docetaxel/carboplatin with celecoxib in patients (pts) with advanced non-small cell lung cancer (NSCLC). The NVALT-4 study. Proc Am Soc Clin Oncol, 2009, abstract ID 8005 Wymenga ANM, Biesma B, Vincent A, Dalesio O, Groen HJM. Is there a role for Complete Geriatric Assessment (CGA) in the treatment of elderly non-small cell lung cancer (NSCLC) patients (pts) receiving combination chemotherapy? Final results from prospective

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multicenter NVALT-3 study. Proc Am Soc Clin Oncol, 2009. Biesma B. Interpretatie van studieresultaten. Cursus ”Oncologie voor de longarts”. Terschelling 15-19 maart 2009. Biesma B. Chemotherapie voor de oudere patiënt. Cursus ”Oncologie voor de longarts”, Prof. Dr. Jaap Swierenga Stichting. Terschelling 15-19 maart 2009. Biesma B. (Neo-)adjuvante chemotherapie in NSCLC. Curriculum Longoncologie voor longartsen in opleiding. Utrecht 3 april 2009. Biesma B, Jacobs M, Bots A. De patiënt met acute dyspnoe. Geaccrediteerde nascholingscursus voor huisartsen. Vught, 12 mei 2009. Biesma B. Biologicals: een update.


Post WCLC meeting. Vught, 9 september 2009. Biesma B, Lucas A. CASPIR cursus 2009: Praktische spirometrie voor de eerst lijn. Vught, 16 september 2009. Biesma B. Nascholing voor longartsen: het belang en de implicaties van EGFRmutatiebepaling bij het NSCLC. Tyrosine Kinase Inhibitors. ’s-Hertogenbosch 5 november 2009. Biesma B. Statistiek bij longkanker studies. Avondsymposium Longoncologie. Wageningen 14 januari 2010. Biesma B. Nascholing voor longartsen en aios: de rol van TKI’s bij de behandeling van NSCLC. ’s-Hertogenbosch 11 maart 2010. Biesma B. Chemotherapie voor de oudere patiënt. Cursus ”Oncologie voor de longarts”, Prof. Dr. Jaap Swierenga Stichting. Terschelling 14-18 maart 2010.

Biesma B. Bewijsvoering, richtlijnen en veiligheid bij het gebruik van ESA’s. Symposium Groeifactoren. ’s-Hertogenbosch 15 april 2010. Macken T. Voordracht: Rijvaardigheidskeuring bij OSAS. Nederlandse Vereniging SlaapapneuPatienten. ’s-Hertogenbosch, 24 maart 2010. Macken T. Voordracht: COPD. Nascholing huisartsen SCEM, 13 april 2010. Macken T. Caspir nascholing longfunctie. Vught, 19 januari 2010 / 13 juli 2010. Macken T. COPD ketenzorg. Bossche samenscholingsdagen, 26 november 2010. Macken T. Docentschap Ziekteleer Longziekten Master Medische Psychologie,. Universiteit van Tilburg (jaarlijks), september 2010.

Publicaties (niet pubmed) Biesma B. Palliatieve chemotherapie voor de oudere patient. Gamma Professional, 2: 28-32, 2009. De Visser VL, Biesma B. Wat is de beste eerstelijnsbehandeling voor gemetastaseerd bronchoalveolaircel carcinoom. Oncologie Vademecum, 6: 5, 2009.

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MEDISCHE MICROBIOLOGIE Wetenschappelijke publicaties Budding AE, Ingham CJ, Bitter W, VandenbrouckeGrauls CM, Schneeberger PM. The Dienes phenomenon: competition between unrelated strains of Proteus mirabilis. J Bacteriol 2009 Jun;191(12):3892-900. PMID: 19251852 Karagiannis I, Schimmer B, van Lier A, Timen A, Schneeberger PM, van Rotterdam B, de Bruin A, Wijkmans C, Rietveld A, van Duynhoven Y. Investigation of a Q fever outbreak in a rural area of The Netherlands. Epidemiol Infect 2009 Sep;137(9):1283-94. PMID: 19161644 Schimmer B, Dijkstra F, Vellema P, Schneeberger PM, Hackert V, ter Schegget R, Wijkmans C, van Duynhoven Y, van der Hoek W. Sustained intensive transmission of Q fever in the south of the Netherlands, 2009. Euro Surveill 2009;14:pii=19210. PMID: 19442401 Penninx J, Brandes M, de Bruin JP, Schneeberger PM, Hamilton CJ. Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests.

medische microbiologie

Eur J Obstet Gynecol Reprod Biol 2009;147:178-82. PMID: 19733956 de Jager CP, de Wit NC, Weers-Pothoff G, van der Poll T, Wever PC. Procalcitonin kinetics in Legionella pneumophila pneumonia. Clin Microbiol Infect 2009;15:1020-5. PMID: 19438643 Daha TJ, Bilkert-Mooiman MA, Ballemans C, Frijstein G, Keeman JN, de Man RA, van Steenbergen JE, Weers-Pothoff G, Zaaijer HL. Hepatitis B virus infected health care workers in The Netherlands, 2000-2008. Eur J Clin Microbiol Infect Dis 2009;28:1041-4. PMID: 19350292 De Wit NC, de Jager CP, Meekelenkamp JC, Schoorl M, van Gageldonk-Lafeber AB, Leenders AC, Kusters R, Wever PC. Markers of infection in inpatients and outpatients with acute Q-fever. Clin Chem Lab Med 2009;47:1407-9. PMID: 19778289 Van Asten L, van der Lubben M, van den Wijngaard C, van Pelt W, Verheij R, Jacobi A, Overduin P, Meijer A,

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Luijt D, Claas E, Hermans MH, Melchers W, Rossen J, Schuurman R, Wolffs P, Boucher C, Schirm J, Kroes L, Leenders AC, Galama J, Peeters M, van Loon A, Stobberingh E, Schutten M, Koopmans M. Strengthening the diagnostic capacity to detect Bio Safety Level 3 organisms in unusual respiratory viral outbreaks. J Clin Virol 2009; 45:185-90. PMID: 19515608 Chinnadurai SK, Troan BV, Wolf KN, DeVoe RS, Huijsmans CJ, Hermans MH, Wever PC. Septicemia, endocarditis, and cerebral infarction due to Staphylococcus aureus in a harp seal (Phoca groenlandica). J Zoo Wildl Med 2009;40:393-7. PMID: 19569495 Van de Veerdonk FL, de Jager CP, Schellekens JJ, Huijsmans CJ, Beaumont F, Hermans MH, Wever PC. Legionella pneumophila DNA in serum samples during Legionnaires’ disease in relation to C-reactive protein levels. Eur J Clin Microbiol Infect Dis 2009;28:371-6. PMID: 18855027 Schneeberger PM, Hermans MH, van Hannen EJ , Schellekens JJ, Leenders AC, Wever PC. Real-time PCR with serum samples is indispensable for early diagnosis of acute Q fever. Clin Vaccine Immunol. 2010 Feb;17(2):286-90. PMID:20032219 Van Wijk PT, Boland GJ, Voss A, Schneeberger PM. Impact of new guidelines for blood exposure incidents in The Netherlands. Occup Med (Lond). 2010;60:270-6. PMID: 20448058 Van Wijk P, Schneeberger PM, Heimeriks KT, Boland GJ, Karagiannis I, Geraedts J, Ruijs WL. Occupational blood exposure accidents in the Netherlands Eur J Public Health. 2010 Jun; 20(3): 281-7.

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PMID: 19864365 Schimmer B, ter Schegget R, Wegdam M, Züchner L, de Bruin A, Schneeberger PM, Veenstra T, Vellema P, van der Hoek W. The use of a geographic information system to identify a dairy goat farm as the most likely source of an urban Q-fever outbreak. BMC Infect Dis 2010 Mar 16; 10: 69. PMID: 20230650 Van der Hoek W, Dijkstra F, Schimmer B, Schneeberger PM, Vellema P, Wijkmans C, ter Schegget R, Hackert V, van Duynhoven Y. Q fever in the Netherlands: an update on the epidemiology and control measures. Euro Surveill 2010 Mar 25;15(12):pii=19520. PMID: 20350500 Van der Hoek W, Dijkstra F, Rietveld A, Wijkmans CJ, Steenbergen JE, Notermans DW, Schneeberger PM. Three years of Q fever in the Netherlands: faster diagnosis. [Drie Jaar Q-koorts in Nederland: snellere diagnose.] Ned Tijdschr Geneeskd 2010; 154:A1845 PMID: 20619049 Wegdam-Blans MC, Nabuurs-Franssen MH, Horrevorts AM, Peeters MF, Schneeberger PM, Bijlmer HA. Laboratory diagnosis of acute Q fever. [Laboratoriumdiagnostiek van acute Q-koorts.] Ned Tijdschr Geneeskd 2010;154:A2388. PMID: 20858325 Wever PC, Arts CH, Groot CA, Lestrade PJ, Koning OH, Renders NM. Screening for chronic Q fever in symptomatic patients with an aortic aneurysm or prosthesis. [Screening op chronische Q-koorts bij symptomatische patiënt met aneurysma of prothese van de aorta.] Ned Tijdschr Geneeskd 2010;154:A2122. PMID: 20699030


Kusters MA, Gemen EF, Verstegen RH, Wever PC, de Vries E. Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T lymphocytes. Ped Res 2010 May;67(5):557-62. PMID: 20098345 Jager MM, Murk JL, Pique R, Wulf MW, Leenders AC, Buiting AG, Bogaards JA, Kluytmans JA, Vandenbroucke-Grauls CM. Prevalence of carriage of meticillin-susceptible and meticillin-resistant Staphylococcus aureus in employees of five microbiology laboratories in The Netherlands. J Hosp Infect 2010 Mar;74(3):292-4. PMID: 20149482 Munster JM, Leenders AC, van der Hoek W, Schneeberger PM, Rietveld A, Riphagen-Dalhuisen J, Stolk RP, Hamilton CJ, de Vries E, Meekelenkamp J, Lo-Ten-Foe JR, Timmer A, De Jong-van den Berg LT, Aarnoudse JG, Hak E. Cost-effectiveness of a screening strategy for Q fever among pregnant woman in risk areas: a clustered randomized controlled trial. BMC Womens Health. 2010 Nov 1;10:32. PMID: 21040534 Limonard GJ, Nabuurs-Franssen MH, Weers-Pothoff G, Wijkmans C, Besselink R, Horrevorts AM, Schneeberger PM, Groot CA. One-year follow-up of patients of the ongoing Dutch Q fever outbreak: clinical, serological and echocardiographic findings.

Infection 2010 Dec;38(6):471-7. PMID: 20857313 Limonard GJ, Peters JB, Nabuurs-Franssen MH, Weers-Pothoff G, Besselink R, Groot CA, Dekhuijzen PN, Vercoulen JH. Detailed analysis of health status of Q fever patients 1 year after the first Dutch outbreak: a case-control study. QJM 2010 Dec;103(12):953-8. PMID: 20802011 De Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010;14(5):R192. PMID: 21034463 Kampschreur LM, Wegdam-Blans MC, Thijsen SF, Groot CA, Schneeberger PM, Hollander AA, Schijen JH, Arents NL, Oosterheert JJ, Wever PC. Acute Q fever related in-hospital mortality in the Netherlands. Neth J Med 2010 Dec;68(12):408-413. PMID: 21209466 Dijkstra F, Riphagen-Dalhuisen J, Wijers N, Hak E, van der Sande MA, Morroy G, Schneeberger PM, Schimmer B, Notermans DW, van der Hoek W. Antibiotic therapy for acute Q fever in The Netherlands in 2007 and 2008 and its relation to hospitalization. Epidemiol Infect 2010 Nov 19:1-10. PMID: 21087542

Proefschriften Van Wijk P. (copromotor Schneeberger PM) Improving the Management of Blood Exposure Accidents in The Netherlands, Radboud Universiteit Nijmegen, 18 november 2009.


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Abstracts, voordrachten en posters De Jager CP, de Wit NC, Weers-Pothoff G, van der Poll T, Wever PC. Poster: Procalcitonin kinetics in Legionella pneumophila pneumonia. Nederlandse Intensivisten Dagen 2009, Ede, 11-13 februari 2009. Wever PC. Voordracht: Q-koorts, geiten en bioterrorisme. Venticare 2009, Utrecht, 14 mei 2009. De Jager CP, Mathoera RB, de Jongh-Leuvenink J, van Wijk PT, van der Poll T, Wever PC. Poster: Lymphocytopenia and neutrophil/lymphocyte count ratio predict bacteremia better than conventional parameters in an emergency care unit. ECCMID, Helsinki, Finland, 16-19 mei 2009. Schneeberger PM, van Hannen EJ, Schellekens JJ, Leenders AC, Hermans MH, Wever PC. Poster: Real-time PCR is indispensable for early diagnosis of acute Q-fever. ICAAC, San Francisco, USA, 12-15 september 2009. Meiberg AE, van Wijk PT, Dam BA, Groenewold MH, Bruers JJ, Schneeberger PM. Poster: National program on blood-exposure incidents in dental practices in The Netherlands. ICAAC, San Francisco, USA, 12-15 september 2009. Rentenaar RJ, de Jager CP, Schneeberger PM, de Wit NC, Wever PC. Poster: Cytomegalovirus latency does not influence clinical presentation and outcome of infection with Legionella pneumophila serogroup 1. Legionella 2009, Parijs, Frankrijk, 13-17 oktober 2009. Schellekens JJ, Wever PC, Schneeberger PM, van Hannen EJ, Leenders AC, Hermans MH. Voordracht en Poster: Real-time PCR is indispensable for early diagnosis of acute Q-fever. 6th European Meeting on Molecular Diagnostics,

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Scheveningen, 22-23 oktober 2009. Jager MM, Weers-Pothoff G, Hermans MH, Schellekens JJ, Meekelenkamp J, Schneeberger PM, Wever PC. Voordracht: Value of a diagnostic algorithm for the diagnosis of acute Q-fever in an outbreak setting. Symposium Q-koorts: een complexe ziekte, ’s-Hertogenbosch, 5 november 2009. Dijkstra F, Riphagen-Dalhuisen J, Wijers N, Hak E, van der Sande MA, Schneeberger PM, Morroy G, Schimmer B, van der Hoek W. Vooprdracht: Antibiotic therapy for Q fever in the Netherlands in 2007 and 2008 and its relation to clinical course: preliminary results. Symposium Q-koorts: een complexe ziekte, ’s-Hertogenbosch, 5 november 2009. Leenders AC. Voordracht: De ene zwangerschap is de ander (niet)? Symposium Q-koorts: een complexe ziekte, ’s-Hertogenbosch, 5 november 2009. Renders NH. Voordracht: Chronische Q-koorts. Symposium Q-koorts: een complexe ziekte, ’s-Hertogenbosch, 5 november 2009. Kampschreur LM, Wegdam-Blans MC, Thijsen SF, Groot CA, Schneeberger PM, van Eede WL, Stals FS, Hollander AA, Schijen JH, Arents NL, Wever PC. Voordracht: Acute Q-fever-related mortality in the Netherlands. Najaarsvergadering NVMM, Zeist, 24 november 2009. Jager MM, Weers-Pothoff G, Hermans MH, Schellekens JJ, Meekelenkamp JC, Schneeberger PM, Wever PC. Voordracht: Evaluation of a diagnostic algorithm for acute Q-fever in an outbreak setting. ECCMID, Wenen, Oostenrijk, 10-13 april 2010.


Schimmer B, Notermans DW, Harms MG, Reimerink JH, Bakker J, Schneeberger PM, Mollema L, Teunis PF, van Pelt W, van Duynhoven YT. Poster: Seroprevalence of Q fever in The Netherlands just preceding a series of large outbreaks. ECCMID, Wenen, Oostenrijk, 10-13 april 2010. Schneeberger PM, Schimmer B, Dijkstra F, Rietveld A, Notermans D, Wegdam-Blans M, van Duynhoven Y, van Rotterdam BJ, Vellema P, Roest HJ, Wijkmans C, van der Hoek W. Voordracht: Epidemiology and control of Q fever in the Netherlands, 2007-2009. ECCMID, Wenen, Oostenrijk, 10-13 april 2010. Schimmer B, ter Schegget R, Wegdam M, Züchner L, de Bruin A, Schneeberger PM, Veenstra T, Vellema P, van der Hoek W. Poster: The use of a geographic information system to identify a dairy goat farm as the most likely source of an urban Q-fever outbreak. ECCMID, Wenen, Oostenrijk, 10-13 april 2010. Jager MM, Weers-Pothoff G, Hermans MH, Schellekens JJ, Meekelenkamp JC, Schneeberger PM, Wever PC. Voordracht: Evaluation of a diagnostic algorithm for acute Q-fever in an outbreak setting. Voorjaarsvergadering NVMM, Papendal, 20-21 april 2010. Renders NH, Stekelenburg CM, Lestrade PJ, Arts CH, Wever PC. Voordracht: In-hospital screening for Q-fever in patients undergoing elective and emergency aneurysm repair. Voorjaarsvergadering NVMM, Papendal, 20-21 april 2010. Schneeberger PM. Voordracht: Diagnostic Dilemma’s for Q fever. Voorjaarsvergadering NVMM, Papendal, 20-21 april 2010.


Wever PC, van Hannen EJ, Schellekens JJ, van Lokven JW, Schneeberger PM, Zaaijer HL, Hermans MH. Voordracht: Detection of Coxiella burnetii DNA in veterinary samples and supermarket dairy products using routine hospital developed real-time PCR techniques. Voorjaarsvergadering NVMM, Papendal, 20-21 april 2010. Kampschreur LM, Schneeberger PM, Jager MM, Hoepelman AI, Leenders AC, Hermans MH, Wever PC. Poster: Early antibiotic treatment of acute Q-fever does not preclude IgG antibody responses to Coxiella burnetii. Voorjaarsvergadering NVMM, Papendal, 20-21 april 2010. Stekelenburg CM, Renders NH, Lestrade P, Wever PC, Koning OH, Arts CH. Voordracht: Q-koorts screening bij patiënten die een electieve of acute aneurysma operatie ondergaan. Chirurgendagen, Veldhoven, 20-21 mei 2010. Wever PC. Voordracht: Q-koorts, een complexe diagnostiek! Infectieziektenserologie-SKML deelnemersmiddag, Het Trippenhuis, Amsterdam, 27 mei 2010. Wever PC. Voordracht: Diagnostiek en behandeling bij Q-koorts. Bijeenkomst Academische Werkplaats AMPHI, Studiecentrum Soeterbeeck, Ravenstein, 1 juni 2010. Wever PC. Voordracht: Q-koorts. Cursus Serologische Diagnostiek van Infectieziekten, VU Medisch Centrum, Amsterdam, 15-17 juni 2010. Leenders AC. Voordracht: Q & A’s over Q koorts. Schellekens symposium Infecties in de Obstetrie en Gynaecologie, Den Haag, 18 juni 2010.

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Meijer A, Jonges M, Abbink F, Ang W, Beersma T, Bloembergen P, Boucher C, Claas E, Donker G, Gooskens J, Isken L, de Jong A, Leenders AC, van der Lubben M, Mascini E, Niesters B, Oosterheert JJ, Osterhaus A, Riesmeijer R, Riezebos-Brilman A, Schutten M, Sebens F, Stelma F, Swaan C, Timen A, van ’t Veen A, van der Vries E, Wierik M, Koopmans M. Voordracht en Poster: Oseltamivir resistant pandemic A(H1N1) 2009 influenza viruses detected in the Netherlands. Options for the Control of Influenza VII, HongKong, China, 3-7 september 2010. Teunis P, Schimmer B, Leenders AC, Notermans D, Herremans T, Wever PC, Schneeberger PM. Poster: Modeling longitudinal serum antibody responses against Coxiella burnetii phase I and II in patients with acute Q fever. ICAAC, Boston, Verenigde Staten, 12-15 september 2010. Van der Hoek W, Versteeg B, Meekelenkamp JC, Renders NH, Leenders AC, Weers-Pothoff G, Wever PC, Schneeberger PM. Poster: How to identify chronic Q fever with serologic follow-up. ICAAC, Boston, Verenigde Staten, 12-15 september 2010. Van de Sande N, Leverstein M, Muilwijk J, Janssen M, de Neeling H, Leenders A, Schneeberger PM. Poster: Should Pig-MRSA Be Part Of The Dutch ‘Search And Destroy’ Policy For MRSA? ICAAC, Boston, Verenigde Staten, 12-15 september 2010. Van der Meeren BT, Chaganial KD, Pfeiffer A, Gomez E, Ferro JJ, Macome C, Abdul R, van de Vondervoort FJ, Steidel K, Wever PC. Poster: Extremely high prevalence of multi-resistance among uropathogens from hospitalized children in Beira, Mozambique. ICAAC, Boston, Verenigde Staten, 12-15 september 2010.

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Leenders AC. Voordracht: Q & A’s over Q koorts. Stafbijeenkomst. Diaconessenziekenhuis, Utrecht, 14 oktober 2010. Munster JM, Leenders AC, Aarnoudse JG, Hak E, for the Q fever during pregnancy study group, The Netherlands. Poster: A screening strategy for Q fever during pregnancy. ESCAIDE, Lissabon, Portugal, 11-13 november 2010. Hautvast J, Schimmer B, Aangenend H, Lenferink A, Schneeberger PM, Vellema P, van Duijnhoven Y. Poster: Risk factors for Q fever infections in dairy goat farmers’ households in the Netherlands. ESCAIDE, Lissabon, Portugal, 11-13 november 2010. Raven S, Hautvast JL, Herremans T, Leenders AC, Schneeberger PM. Poster: Predictive value of solitary IgM phase II positive serology in acute Q fever; comparison of IFA and ELISA. ESCAIDE, Lissabon, Portugal, 11-13 november 2010. Whelan J, Schimmer B, Vromen H, Schneeberger PM, Meekelenkamp J, van der Hoek W, du Ry van Beest Holle MR. Voordracht: Q fever in culling workers before and after animal culling in the Netherlands, 2010. ESCAIDE, Lissabon, Portugal, 11-13 november 2010. Naesens R, Magerman K, Gyssens I, Leenders AC, Coppens G, Oris E, Craeghs J, Thoelen I, Gabriëls P, Vandevelde M, Forier A, Waumans L, Cartuyvels R. Poster : Q-fever in Belgian Limburg: myth or reality? Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, 18-19 november 2010. Van den Brom R, Schimmer B, Schneeberger PM, Swart W, van der Hoek W, Vellema P. Poster: Seroepidemiological survey for Coxiella bunetii antibodies and associated risk factors in Dutch livestock veterinarians.


Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, 18-19 november 2010. Herremans T, Hogema B, Galama J, Peeters M, Nijhuis C, Notermans D, Nabuurs M, Schneeberger PM, Wegdam M, Horrevorts A, van Loo I, Vlaminckx B, Zaaijer H, Koopmans M, Berkhout H, Bijlmer H. Voordracht: Comparison of the performance of CFA, IFA and ELISA assays for the serodiagnosis of Q fever by quality assessment. Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, 18-19 november 2010. Renders NH. Voordracht: Chronic Q fever, a previously rare disease in the Netherlands. Najaarsvergadering NVMM/VIZ/ BVIKM, Amsterdam, 18-19 november 2010.

Kampschreur LM, de Vries Feyens CA, Renders NH, Hermans MH, Oosterheert JJ, Lestrade PJ, Elsman P, Wever PC. Voordracht: Chronic Q-fever related dual pathogen endocarditis: case reports of three patients. Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, 18-19 november 2010. Vissers E, de Jager CP, Kusters R, van Gageldonk-Lafeber AB, Wever PC. Poster: Hypophosphatemia and prolonged length of hospital stay in seronegative PCR positive patients with early acute Q-fever. Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, 18-19 november 2010.

Publicaties (niet pubmed) Schneeberger PM. Het mysterie van de Q-koorts. Mednet 2009:5;20 Steggerda LM, van der Hoek W, Schimmer B, Schneeberger PM, Opstelten W, Oldelohuis A, Hak E. Q-koorts in de huisartsen praktijk: de stand van zaken. Patient Care 2009; juni:7-11. Meekelenkamp JC, Notermans DW, Rietveld A, Marcelis JH, Schimmer B, Reimerink J, Vollebergh J, Wijkmans CJ, Leenders AC. Seroprevalentie van Coxiella burnetii bij zwangere vrouwen in Noord-Brabant in 2007. Infectieziektenbull 2009;20:57-61. Leenders AC. Operatie in beeld. Medisch Contact 2009;64:345.


Leenders AC, Pelk MP, Oosting JD, Brenninkmeijer BJ, van ’t Hullenaar NG. Handvat voor BOA-incidenten. Medisch Contact 2009:64:1102. De Groot AC, van Meurs T, de Jager CP, Bosma J, Wever PC, Stoof TJ. Necrotiserende fasciitis: kliniek, diagnostiek en behandeling. Ned Tijdschr Dermatol Venereol 2009;19:123-9. Van Gageldonk-Lafeber R, van der Lubben M, de Jager CP, Wever PC. Tussenrapportage van de ‘VLO-CAP studie’. Community-acquired pneumonia. Cura 2009;6(1):9-10. De Jager CP, Leuken M, Wever PC. Pylephlebitis; septische tromboflebitis van de poortader en mesenteriaal vaten. Cura 2009;6(2):13.

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Van Kuilenburg JT, Wever PC, de Jager CP. Bijzondere ziektebeelden op de Intensive Care; Morbus Strangularis. Cura 2009;6(3):10. Wever PC. Is het zinvol om peracute cito-diagnostiek te verrichten naar de immuunstatus voor parvovirus B19 bij een zwangere met een parvoviruscontact binnen het gezin? Labcontact 2009;10(28):1-2. Wever PC, Hermans MH. Wat zijn de nieuwe ontwikkelingen in de diagnostiek van acute Q-koorts? Labcontact 2009;10(29):3-4. Wever PC. Q-koorts versus de media. Ned Tijdschr Med Microbiol 2010;18:26. Schneeberger PM. Wits and no genes. Ned Tijdschr Med Microbiolog 2010;18:7-8. Daha TJ, Bilkert-Mooiman MA, Ballemans C, Frijstein G, Keeman JN, de Man RA, van Steenbergen JE, Weers-Pothoff G, Zaaijer HL. Gezondheidszorgmedewerkers met hepatitis B in Nederland, 2000-2008. Infect Bull 2010;21:online publicatie. Wever PC. Waarom lees je niet: ‘Pas op Q-koorts’? De Volkskrant, 20 juni 2009. Wever PC. Zo vlot bij de griep, zo traag bij de Q-koorts. NRC Handelsblad, 11 december 2009.

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MOLECULAIRE DIAGNOSTIEK Wetenschappelijke publicaties Van de Veerdonk FL, de Jager CP, Schellekens JJ, Huijsmans CJ, Beaumont F, Hermans MH, Wever PC. Legionella pneumophila DNA in serum samples during Legionnaires’ disease in relation to C-reactive protein levels. Eur J Clin Microbiol Infect Dis. 2009 Apr;28(4):371-6. PMID: 18855027 trefwoorden: Legionella pneumophila, PCR

Lippert E, Girodon F, Hammond E, Jelinek J, Reading NS, Fehse B, Hanlon K, Hermans M, Richard C, Swierczek S, Ugo V, Carillo S, Harrivel V, Marzac C, Pietra D, Sobas M, Mounier M, Migeon M, Ellard S, Kröger N, Herrmann R, Prchal JT, Skoda RC, Hermouet S. Concordance of assays designed for the quantification of JAK2V617F: a multicenter study. Haematologica. 2009 Jan;94(1):38-45. PMID: 19001280 trefwoorden: JAK2V617F, MPD

Schmeits PC, Péquériaux NC, van Geest-Daalderop JH, Ouwehand ME, Coremans AM, Hermans MH, Conemans JM. Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin. Neth J Med. 2009 Feb;67(2):76-8.

moleculaire diagnostiek

PMID: 19299851 trefwoorden: VKORC1, INR

Van Asten L, van der Lubben M, van den Wijngaard C, van Pelt W, Verheij R, Jacobi A, Overduin P, Meijer A, Luijt D, Claas E, Hermans M, Melchers W, Rossen J, Schuurman R, Wolffs P, Boucher C, Schirm J, Kroes L, Leenders S, Galama J, Peeters M, van Loon A, Stobberingh E, Schutten M, Koopmans M. Strengthening the diagnostic capacity to detect Bio Safety Level 3 organisms in unusual respiratory viral outbreaks. J Clin Virol. 2009 Jul;45(3):185-90. PMID: 19515608 Erratum in: J Clin Virol. 2010 Feb;47(2):204. trefwoorden: diagnostiek, pandemie

Meijer A, Beerens A, Claas E, Hermans M, de Jong A, Molenkamp R, Niesters H, Overduin P, Rossen J, Schuurman R, Wolffs P, Fouchier R, Osterhaus A, Schutten M, Koopmans M. Preparing the outbreak assistance laboratory network in the Netherlands for the detection of the influenza virus A(H1N1) variant. J Clin Virol. 2009 Jul;45(3):179-84. PMID: 19540155 trefwoorden: Influenza, pandemie

Chinnadurai SK, Troan BV, Wolf KN, DeVoe RS,

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Huijsmans CJ, Hermans MH, Wever PC. Septicemia, endocarditis, and cerebral infarction due to Staphylococcus aureus in a harp seal (Phoca groenlandica). J Zoo Wildl Med. 2009. 40:393. PMID: 19569495

Schellekens JJ, Leenders AC, Wever PC. Real-time PCR with serum samples is indispensable for early diagnosis of acute Q fever. Clin Vaccine Immunol. 2010 Feb;17(2):286-90. PMID: 20032219 trefwoorden: Q fever, diagnosis

trefwoorden: harp seal, Staphylococcus aureus

Hermans MH, Poodt J, van Geest-Daalderop JH, Péquériaux NC, Conemans JM. Resistance to coumarin derivatives due to mutated vitamin-K enzyme. Ned Tijdschr Geneeskd. 2009;153:A691. PMID: 19857286 trefwoorden: VKORC1, coumarines

Tilburg JJ, Melchers WJ, Pettersson AM, Rossen JW, Hermans MH, van Hannen EJ, Nabuurs-Franssen MH, de Vries MC, Horrevorts AM, Klaassen CH. Interlaboratory evaluation of different extraction and real-time PCR methods for the detection of Coxiella burnetii DNA in serum. J Clin Microbiol. 2010 Nov;48(11):3923-7. PMID: 20826645 trefwoorden: Q fever, PCR

Schmeits PC, Hermans MH, van Geest-Daalderop JH, Poodt J, de Sauvage Nolting PR, Conemans JM. VKORC1 mutations in patients with partial resistance to phenprocoumon. Br J Haematol. 2010 Mar;148(6):955-7. PMID: 19961479 trefwoorden: VKORC1, mutatie

Schneeberger PM, Hermans MH, van Hannen EJ,

Huijsmans CJ, Damen J, van der Linden JC, Savelkoul PH, Hermans MH. Comparative analysis of four methods to extract DNA from paraffin-embedded tissues: effect on downstream molecular applications. BMC Res Notes. 2010 Sep 14;3:239. PMID: 20840759 trefwoorden: paraffine, DNA extractie

Abstracts, voordrachten en posters Trienekens TA, Broeren M, Linssen ET, Roorda L, Hermans MH. Poster: Evaluation of Becton Dickinson GeneOhm, Hain GenoType MRSA Direct and two in house assays for MRSA screening. Antonie van Leeuwenhoek 95: 109: P076, Papendal, 2009. Trienekens TA, van der Velden JJ, Heumassej AW, Hermans MH. Poster: Performance of Becton Dickinson GeneOhm Methicillin-resistent Staphylococcus aureus PCR assay in different spa- and PFGE-types of MRSA. Antonie van Leeuwenhoek 95: 109: P077, Papendal, 2009.

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Zee, A van der, Hermans MH, Kroonen R, Breugelmans AJ, Mooy N, Westenend PJ. Poster: Evaluation of an internally controlled semiquantitative real-time PCR for detection of Pneumocystis jiroveci in paraffin-embedded clinical samples. European Meeting on Molecular Diagnostics, Scheveningen, 22/23-10-2009. Geraats CW, Catsburg A, Savelkoul P, Hermans MH. Poster: Evaluation of a commercial real time PCR test (Presto CT/NG Test) for simultaneous detection of CT and NG. European Meeting on Molecular Diagnostics, Scheveningen, 22/23-10-2009.


Poodt J, Schmeits PC, Van Geest-Daalderop JH, Conemans JM, Hermans MH. Poster: Patients with partial resistance to acenocoumarol and phenprocoumon; screening the VKORC1 gene. European Meeting on Molecular Diagnostics, Scheveningen, 22/23-10-2009. Poodt J, Hermans MH. Poster: Ultra-sensitive and fast detection of the JAK2V617F mutation in patients with a myeloproliferative disease. European Meeting on Molecular Diagnostics, Scheveningen, 22/23-102009.

Poodt J. Voordracht:Patients with partial resistance to acenocoumarol and phenprocoumon; screening the VKORC1 gene. European Meeting on Molecular Diagnostics, Scheveningen, 22-10-2009. Hermans M. Voordracht: Real-time PCR is indispensable for early diagnosis of acute Q-fever. European Meeting on Molecular Diagnostics, Scheveningen, 23-10-2009.

Zee A van der, Hermans M, Kroonen R, Breugelmans A-J, Mooy N, Westenend PJ. Poster: Evaluation of an internally controlled semiquantitative real-time PCR for detection of Pneumocystis jiroveci in paraffin-embedded clinical materials. European Meeting on Molecular Diagnostics, Scheveningen, 22/23-10-2009. Schellekens J, Wever P, Schneeberger P, van Hannen E, Leenders A, Hermans M. Poster: Real-time PCR is indispensable for early diagnosis of acute Q-fever. European Meeting on Molecular Diagnostics, Scheveningen, 23-10-2009. Huijsmans CJ, Damen J, van der Linden JC, Savelkoul PH, Hermans MH. Poster: Comparison of four methods to extract DNA from paraffin embedded tissues for molecular applications. European Meeting on Molecular Diagnostics, Scheveningen, 2 3-10-2009 en Pathologendagen Zeist, 7/8-4-2010. Huijsmans R. Voordracht: Patientenverwisselingen binnen de pathologie. Congres Vereniging Analisten Pathologie (VAP), Jaarbeurs Utrecht, 15-09-2009.

moleculaire diagnostiek

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Onderzoekstalenten aan boord halen

Hij praat enthousiast over DNA, celmembranen, vetten, eiwitten en suikers. Ook gaat zijn bloed sneller stromen op het moment dat hij micro-organismen bestudeert. Al met al heeft hij een passie voor moleculaire diagnostiek. Dat moet hij even uitleggen… Ronald Huijsmans is promovendus bij het Jeroen Bosch Ziekenhuis en daarnaast unithoofd van de afdeling Moleculaire Diagnostiek. Hij vertelt meer over zijn achtergrond: “Aan het einde van mijn studie Hogere Laboratorium Opleiding kwam ik in aanraking met een moleculair bioloog van dit ziekenhuis. Ik kreeg de mogelijkheid hier een afstudeerstage te volgen. Daarna behaalde ik een master en nu promoveer ik bij de Vrije Universiteit in Amsterdam. Ik had het hier altijd naar mijn zin en ben er trots op dat ik mijn promotieonderzoek in dit ziekenhuis kan afronden.”

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Vingerafdruk Het project van Huijsmans richt zich specifiek op het onderzoeken van de zogenaamde Single Nucleotide Polymorphism (SNP). “De afkorting SNP wordt uitgesproken als snip. Het DNA bestaat simpel gezegd uit vier bouwstenen: A, C, T en G. Een SNP is een variatie van zo’n bouwsteen. Persoon 1 heeft op een bepaalde plaats in het DNA een A, persoon 2 heeft op die plek een C. Alle levensvormen hebben een groot aantal van deze SNP’s. Door een slimme combinatie van SNP’s te gebruiken, kun je veel toepassingen onderzoeken. Ik zie het als een vingerafdruk van ieder levend organisme.” Snel, goedkoop en eenvoudig Huijsmans: “Om DNA te onderzoeken moeten we het eerst zuiveren van allerlei celmateriaal, zoals eiwitten, membranen en celorganellen. Dit noemen we DNA-isolatie. Vervolgens stelt de SNP-technologie ons in staat snel, goedkoop en relatief eenvoudig genetische kenmerken uit het DNA in kaart te brengen.” En dat is niet het enige: “Er is minder materiaal nodig om tot een genetische afdruk van een persoon, tumor of micro-organisme te komen. De SNP-technologie is geschikt voor het werken met sterk gedegradeerd DNA, vaak het geval bij weefsels van de pathologie” Toepassingen We gebruiken deze techniek voor een aantal toepassingen. Huijsmans: “Zo kijken we naar SNP’s wanneer er mogelijk een monster verwisseld is. Een andere toepassing is het SNP-onderzoek waarbij we kijken naar het verlies of juist de vermeerdering van bepaalde genen die kunnen leiden tot het ontstaan van kanker. In Nederland was de afgelopen jaren de grootste Q-koorts uitbraak ter wereld. Dit is een zeer besmettelijke infectieziekte die van dieren over kan gaan op mensen. Ook hier hebben we de SNPtechniek ingezet.” Samenwerking “De Q-koorts wordt veroorzaakt door de bacterie Coxiella burnetii”, vervolgt Huijsmans. “Met de SNP-techniek ontdekten we maar liefst vijf verschillende typen bacteriën. Daarnaast toonden we met deze test aan dat het DNA uit het Q-koorts vaccin in de melk van gevaccineerde geiten terechtkomt. Naar aanleiding van deze bevinding is op landelijk niveau de tijd tussen vaccinatie en het nemen van een diagnostisch tankmelk monster aangepast. Dat zou ons niet gelukt zijn zonder het doen van onderzoek. Ook was er steeds goede samenwerking met artsen en andere paramedici. Dit topklinische ziekenhuis heeft dan ook de ambitie onderzoekstalenten aan boord te halen!”

interview ronald huijsmans

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NEUROLOGIE Wetenschappelijke publicaties Jongen PJ, Sindic C, Carton H, Zwanikken C, Lemmens W, Borm G; Functional composite and quality of Life in Avonex-treated Relapsing multiple sclerosis patients study group. Anten, Driessen, Baard, Frequin, Hintzen, Hupperts, Jongen, Linssen, MispelblomBeyer, Moll, van Munster, Pratzsky, Sanders, Smits, van Walbeek, Willems, Witjes, van Zuilen, Bartholomé, Braeckveldt, Van der Motte, Debruyne, Decoo, Dedeyn, Engelborghs, Dupuis, Jacquerye, Van de Gaer, Guillaume, Reznik, Harmant, D’Hooghe, Klippel, Willems, van Landegem, Strauven, Maertens de Noordhout, Delavaux, Nagels, Seeldrayers, Vervonck, Sindic, Goffette, El-Memar, Hawkins, de Diego. Improvement of health-related quality of life in relapsing remitting multiple sclerosis patients after 2 years of treatment with intramuscular interferonbeta-1a. J Neurol. 2010 Apr;257(4):584-9. PMID: 19921303 Sleegers MJ, Beutler JJ, Hardon WJ, Berden JH, Verhave JC, Conemans JM, Hollander DA, Dautzenberg PL., Hoogeveen EK. Reversible rapidly progressive dementia with parkinsonism induced by valproate in a patient with systemic lupus erythematosus. J Am Geriatr Soc. 2010. Apr; 58(4): 799-801. PMID: 20398172

neurologie

Trefwoorden: Dementie en valproïnezuur

Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen MP, van Doorn PA, Steyerberg EW, Jacobs BC. Prediction of respiratory insufficiency in Guillain-Barré syndrome. Ann Neurol. 2010 Jun;67(6):781-7. PMID: 20517939 Van Nes SI, Vanhoutte EK, Faber CG, Garssen MP, van Doorn PA, Merkies IS; PeriNomS Study Group. Improving fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity scale. J Peripher Nerv Syst. 2009 Dec;14(4):268-78. PMID: 20021568 Bernsen RA, de Jager AE, Kuijer W, van der Meche FG, Suurmeijer TP. Psychosocial dysfunction in the first year after Guillain-Barre syndrome. Muscle Nerve 2010 Apr;41(4):533-9. PMID: 19941334 Trefwoorden: Guillain-Barre syndrome, psychosocial.

Verra WC, Snijders TJ, Seute T, Han KS, Nieuwenhuis HK, Rutten GJ. Myeloid Sarcoma presenting as a recurrent, multifocal

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nerve root entrapment syndrome. J Neurooncol. 2009 Jan;91(1):59-62. PMID: 18712278 Rutten GJ, Ramsey NF. The role of functional magnetic resonance imaging in brain surgery. Neurosurg Focus 2010 Feb;28(2): E4. PMID: 20121439

Munneke M, Nijkrake MJ, Keus SH, Kwakkel G, Berendse HW, Roos RA, Borm GF, Adang EM, Overeem S, Bloem BR; ParkinsonNet Trial Study Group.(ter Bruggen JP) Efficacy of community-based physiotherapy networks for patients with Parkinson’s disease: a clusterrandomised trial. Lancet Neurol. 2010 Jan;9(1):46-54. PMID: 19959398

Keus SH, Nijkrake MJ, Borm GF, Kwakkel G, Roos RA, Berendse HW, Adang EM, Overeem S, Bloem BR, Munneke M; ParkinsonNet Trial Study Group. (ter Bruggen JP) The ParkinsonNet trial: design and baseline characteristics. Mov Disord. 2010 May 15;25(7):830-7. PMID: 20461799

Robben SH, Sleegers MJ, Dautzenberg PL, van Bergen FS, ter Bruggen JP, Rikkert MG. Pilot study of a three-step diagnostic pathway for young and old patients with Parkinson’s disease dementia: screen, test and then diagnose. Int J Geriatr Psychiatry. 2010 Mar; 25(3):258-65. PMID: 19582760

Abstracts, voordrachten en posters Jongen PJ, van Munster ETh. Poster: Retrospective study on predictors of a favourable outcome of Mitoxantrone treatment in patients with multiple sclerosis. ECTRIMS Dusseldorf 2009. Reijmers R, van Munster ETh. e.a. Poster: Functional ambulation and handfunction improves while using natalizumab in multiple sclerosis. ECTRIMS Goteborg, 15 oktober 2010. Vennegoor A, van Munster ETh. e.a Poster: Indolent course of progressive multifocal leukoencephalopathy during natalizumab treatment in multiple sclerosis. ECTRIMS Goteborg, 15 oktober 2010. van Munster ETh. Kwaliteitsdag zorgverzekeraars. 26 januari 2009. van Munster ETh.

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Minisymposium WDH; nieuwe ontwikkelingen. 15 april 2009. van Munster ETh. Voordracht: Mutiple Sclerose, wat hebben we te bieden? Symposium voor fysiotherapeuten, 12 mei 2009. van Munster ETh. Metaplansessie Parkinson. 16 september 2009. van Munster ETh. Verleden, heden en toekomst. Landelijk symposium Multiple Sclerosis, 9 en 10 oktober 2009. van Munster ETh. Neuromyelitis optica, huidige inzichten en parktische handvaten. Landelijk symposium Multiple Sclerosis de komende 5 jaar, 5 en 6 november 2009.


van Munster ETh. MS patiënten bijeenkomst DUET. 6 november 2009. van Munster ETh. Wereldwijd onerzoek bij MS. Nationale MS-dag, 28 november 2009. van Munster ETh. Regionaal MS fysiotherapie netwerk. 15 januari 2010. van Munster ETh. Neurologie in ontwikkeling. Rotary, 3 februari 2010. van Munster ETh. MS en multidisciplinair overleg. MSVN, 16 juni 2010. van Munster ETh. Kwaliteitsdag zorgverzekeraars. 11 oktober 2010.

Van Nes SI, Vanhoutte EK, Faber CG, Garssen MP, van Doorn PA, Merkies IS, on behalf of the PeriNomS study group. Improving Fatigue assessment in immune-mediated neuropathies: The modified Rasch-built Fatigue Severity Scale. Peripheral Nerve Society 2009. Garssen MP. Voordracht: Het Guillain-Barré syndroom, bespoedigen van het herstel. Venticare, nationaal intensive care congres, 2010. Rutten GJ. A short history of functional neuroimaging. Symposium Functional Neuro-Imaging: new clinical applications. Hilvarenbeek, 26 juni 2009. Rutten GJ. Herstellen en voorspellen: neuropsychologisch onderzoek bij patienten met een hersenaandoening. Symposium “de geest uit de fles: medisch psychologisch onderzoek in het St Elisabeth Ziekenhuis”, CORPS, Tilburg, april 2010.

Publicaties (niet pubmed) Jongen PJ, Lehnick D, Sanders E, S eeldragers P, Frederikson S, Anderson M, Speck J, Focus Study Group (van Munster ETh, e.a.). Health related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatirameracetate: a prospective, observational, international, multi-centre study. Health and quality of life outcomes 2010,8:133-140. Jeene PM, van Munster ETh, Louwerse ES. Pergolidegebruik, benauwdheid en oedeem; altijd klepfibrose? Tijdschrift voor neurologie en neurochirurgie 2010;111:160-2 .

neurologie

van Munster ETh. Copaxone: een remmende medicatie. Uitgave van national ms fonds 2010. White CM, van Doorn PA, Garssen MPJ, Stockley RC. Interventions for fatigue in peripheral neuropathy. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD008146. DOI:10.1002/14651858. Rutten GJ, op de Coul B, Verschoor N. Cervicale hyperostosis als behandelbare oorzaak voor dysfagie. Nederlands Tijdschrift voor Keel- Neus en Oorheelkunde, 2009;15(1):29-31.

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Rutten GJ, Vincent AJ, Gosselaar PH, de Witt Hamer PC. Vroege resectie voor een vermoedelijk laaggradig glioom. Tijdschrift voor Neurologie en Neurochirurgie; 111:72-78, 2010 Jeene P, ter Bruggen JP. Duodenal Duodopa in MSA-P. Movement disorders. Supplement: 2010: 25: 2 Jeene PM, ter Bruggen JP. Depressie bij de ziekte van Parkinson. Neurologie Aktueel: 6: juli 2009 ter Bruggen JP. Chronische vermoeidheid bij de ziekte van Parkinson en MS. Script neurologie: juli 2010

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NUCLEAIRE GENEESKUNDE Wetenschappelijke publicaties Hoetjes NJ, van Velden FH, Hoekstra OS, Hoekstra CJ, Krak NC, Lammertsma AA, Boellaard R. Partial volume correction strategies for quantitative FDG PET in oncology. Eur J Nucl Med Mol Imaging. 2010 Aug;37(9):1679-87. PMID: 20422184 Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, Oyen WJ, Kotzerke J, Hoekstra OS, Pruim J, Marsden PK, Tatsch K, Hoekstra CJ, Visser EP, Arends B, Verzijlbergen FJ, Zijlstra JM, Comans EF, Lammertsma AA, Paans AM, Willemsen AT, Beyer T, Bockisch A, Schaefer-Prokop C, Delbeke D, Baum RP, Chiti A, Krause BJ.

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010 Jan;37(1):181200. PMID: 19915839 Dassen AE, Lips DJ, Hoekstra CJ, Pruijt JF, Bosscha K. FDG-PET has no definite role in preoperative imaging in gastric cancer. Eur J Surg Oncol. 2009 May;35(5):449-55. PMID: 19147324

Abstracts, voordrachten en posters Hoekstra CJ FDG PET respons monitoring bij het maligne lymfoom HOVON Roadshow Dordrecht en Amersfoort, 2009.

nucleaire geneeskunde

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OOGHEELKUNDE Wetenschappelijke publicaties Van Meel G. Voordracht: “laserbehandeling van diabetische retinopathie”. De landelijke laserdag voor oogartsen in Nijmegen, 13 februari 2010.

oogheelkunde

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ORTHOPEDIE Wetenschappelijke publicaties Rutten MJ, Spaargaren GJ, van Loon T, de Waal Malefijt MC, Kiemeney LA, Jager GJ. Detection of rotator cuff tears: the value of MRI following ultrasound. Eur Radiol. 2010 Feb;20(2):450-7. PMID: 19727754

A Prospective, Randomized, Controlled, Multicenter Study of Osteogenic Protein-1 in Instrumented Posterolateral Fusions. Report on Safety and Feasibility. SPINE (Phila Pa 1976). 2010 May 20;35(12):1185-91. PMID: 20445470 Trefwoorden:”OP1, posterolateral fusion

Delawi D, Dhert WJ, Rillardon L, Gay E, Prestamburgo D, Garcia-Fernandez C, Guerado E, Specchia N, Van Susante JL, Verschoor N, Quarles van Ufford HM, Oner FC.

Publicaties (niet pubmed) Rutten GJ, op de Coul B, Verschoor N. Cervicale hyperostosis als behandelbare oorzaak voor dysfagie. Nederlands Tijdschrift voor Keel- Neus en Oorheelkunde, 2009;15(1):29-31. Trefwoorden: DISH, dysfagie

orthopedie

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PATHOLOGIE Wetenschappelijke publicaties Giard RW, Broekman JM. Missed malignant melanoma: legal considerations Ned Tijdschr Geneeskd. 2009;153:A1237. PMID: 20015414 van la Parra RF, Ernst MF, Bevilacque JL, Mol SJ, van Zee KJ, Broekman JM, Bosscha K. Validation of a nomogram to predict the risk of nonsentinal lymph node metastases in breast cancer patients with a positive sentinel node biopsy: Validation of the MSKCC breast nomogram. Ann Surg. Oncol. 2009 May; 16(5)11285-35 PMID: 19252954 Van Wensen RJA, Bosscha K, Jager GJ, van der Linden JC, Fijnheer R. Een ruimteinnemend proces in het pancreas. Niet altijd een carcinoom. [An invasive process in the pancreas: sometimes lymphoma.] Ned Tijdschr Geneeskd. 2009;153:B164. Dutch. PMID: 19818177 Van Schaik PM, Hermans E, van der Linden JC, Pruijt JR, Ernst MF, Bosscha K.

pathologie

Micro-metastases in stages I and II colon cancer are a predictor of the development of distant metastases and worse disease-free survival. Eur J Surg Oncol. 2009 May;35(5):492-6. PMID: 18775627 Ritchie ED, Jager GJ, van der Linden JC, Bosscha K. Three adults with intra-abdominal lymphangioma. Ned Tijdschr Geneeskd. 2009 Mar 7;153(10):456-9. PMID: 19374097 Meijer RP, Gemen EF, van Onna IE, van der Linden JC, Beerlage HP, Kusters GC. The value of an artificial network in the decisionmaking for prostate biopsies. World J Urol. 2009 Oct;27(5):593-8. PMID 19562346 Huijsmans CJ, Damen J, van der Linden JC, Savelkoul PH, Hermans MH. Comparative analysis of four methods to extract DNA from paraffin-embedded tissues: effect on downstream molecular applications. BMC Res Notes. 2010 Sep 14;3:239. PMID: 20840759

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Abstracts, voordrachten en posters Meijer RP, Gemen EF, Onna IE, van der Linden JC, Kusters GC. Poster: The valus of an artificial network in the decision making for prostate biopsies. Congres Nederlandse Vereniging voor Klinische Chemie (NVKC) 24-25 april 2009. Huijsmans CJ, Damen J, van der Linden JC, Savelkoul PH, Hermans MH. Poster: Comparison of four methods to extract DNA from paraffin embedded tissues for molecular applications. European Meeting on Molecular Diagnostics, Scheveningen, 23-10-2009 en Pathologendagen Zeist, 7/8-4-2010.

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PLASTISCHE CHIRURGIE Wetenschappelijke publicaties Kenis H, Zandbergen HR, Hofstra L, Petrov AD, Dumont EA, Blankenberg FD, Haider N, Bitsch N, Gijbels M, Verjans JW, Narula N, Narula J, Reutelingsperger CP. Annexin A5 Uptake in Ischemic Myocardium: Demonstration of Reversible Phosphatidylserine Externalization and Feasibility of Radionuclide Imaging. Journal of Nuclear Medicine Vol. 51 No. 2 259-267, 2010. Dumont EA, Lutgens SP, Reutelingsperger CP, Bos GM, Hofstra L. Minocycline Inhibits Apoptotic Cell Death in a Murine Model of Partial Flap Loss. J reconstr Microsurg 2010; 26(8): 523-528.

de With MC, de Vries AM, Kroese AB, van der Heijden EP, Bleys RL, Segal SS, Kon M. Vascular anatomy of the hamster retractor muscle with regard to its microvascular transfer. Eur Surg Res. 2009;42(2):97-105. PMID: 19088476 de Wijn RS, van der Heijden EP, Kon M. On lipoma of the buccal fat pad: report of two cases and review of the literature. J Plast Reconstr Aesthet Surg. 2009 Jan;62(1):28-35. PMID: 18249050

Schouten HW, Knippels MC, Franken RJ. Maggots in the wound, debridement, disinfection and wound healing. Ned Tijdschr Geneeskd. 2009;153:A624. PMID: 19900320 de With MC, van der Heijden EP, van Oosterhout MF, Kon M, Kroese AB. Contractile and morphological properties of hamster retractor muscle following 16 h of cold preservation. Cryobiology. 2009 Dec;59(3):308-16. PMID: 19733556

plastische chirurgie

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Abstracts, voordrachten en posters Franken RJ De Hand: Geneeskunde of geneeskunst? Nederlandse OK dagen, RAI Amsterdam, 5 en 6 oktober 2010. Van der Heijden EP CMC1 arthrosis: diagnostiek en behandeling Scholingsdag revalidatieartsen in opleiding, ’s-Hertogenbosch, februari 2009.

Van der Heijden EP Diagnostiek en behandeling van dupuytren en mallet vinger Informatie avond fysiotherapeuten verzorgd door handpolsexpertise centrum JBZ (HPEC), ’s-Hertogenbosch, augustus 2010. Van der Heijden EP Artrose van de handgewrichten en de operatieve behandelopties Bossche Samenscholingsdagen, Vlissingen, november 2010.

Publicaties (niet pubmed) Rutten MJ, Setz-Pels W, Hermens RA, Franken RJ. Nieuwe CT-angiografie toepassing verkort borstreconstructie. Cura, jaargang 6, nr 3, dec 2009, blz 17. Trefwoorden: borstreconstructie, CT-angiografie

Hermens RA, Franken RJ, Setz-Pels W, Rutten MJ. Opereren aan de hand van een landkaart. JBZ Palet, jaargang 5, nr 8, dec 2009. Trefwoorden: borstreconstructie, CT-angiografie

Setz-Pels W, Rutten MJ, Franken RJ, Hermens RA. Jeroen Bosch Ziekenhuis gebruikt nieuwe methode bij borstreconstructie. Medicalfacts: 20 jan 2010, Thuis in het nieuws: 23 jan 2010, Brug Berlicum eo: 28 jan 2010. Trefwoorden: borstreconstructie, CT-angiografie

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RADIOLOGIE Wetenschappelijke publicaties Rutten MJ, Collins JM, Maresch BJ, Smeets JH, Janssen CM, Kiemeney LA, Jager GJ. Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MRarthrography. European Radiology, 2009; 19 (3):722-730. PMID: 18958474 Trefwoorden: Echogeleide punctie, schouder

Vugt R, Bosscha K, van Munster IP, de Jager CP, Rutten MJ. Embolization as Treatment of Choice for Bleeding Peptic Ulcers in High Risk Patrients. Digestive surgery 2009;26(1):37-42 (DOI: 10.1159/000193476). PMID: 19155626. Trefwoorden: Gastro-enterale bloeding, embolisatie

Ploegmakers MJ, Rutten MJ. Fatal pericardial tamponade after superior vena cava stenting. CardioVascular Interventional Radiology 2009 May;32(3):585-9. PMID: 18855048 Trefwoorden: Vena cava superior, stent

Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek EJ, Braam BB, Huysmans FT, Schultze Kool LJ, Rutten MJ, Doorenbos CJ, Aarts HC, Rabelink TJ,

radiologie

Plouin PF, Raynaud A, van Montfrans GA, Reekers JA, van den Meiracker AH, Pattynama PM, van de Ven PJ, Vroegindeweij D, Kroon BA, de Haan MW, Postma CT, Beutler JJ. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med 2009 Jun 16;150(12):840-8. PMID: 19414832 Trefwoorden: a renalis stenose, stent

Rutten MJ, Spaargaren GJ, van loon T, de Waal Malefijt MC, Kiemeney LA, Jager GJ. Detection of rotator cuff tears: the value of MRI following ultrasound. European Radiology, 2010; 20 (2):450–457. DOI 10.1007/s00330-009-1561-9 PMID: 19727754. Trefwoorden: Schouderechografie, rotator cuff rupturen

Rutten MJ, Collins JM, de Waal Malefijt MC, Kiemeney LA, Jager GJ. Unsuspected sonographic findings in patients with post-traumatic shoulder complaints. J Clin Ultrasound. 2010 Nov;38(9):457-65. PMID: 20848574 Trefwoorden: Schouder trauma, echografie

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Rutten MJ, de Jong MD, van Loon T, Jager GJ. Intratendinous ganglion of the long head of the biceps tendon: US and MRI features (2010: 9b). Intratendinous ganglion. Eur Radiol. 2010 Dec;20(12):2997-3001. PMID: 21069528 van der Horn G, Ranschaert ER, Dubelaar IJ, van Munster IP. An adult with vague abdominal complaints and atypical colonoscopic findings. Neth J Med. 2010 Aug;68(1):324-7. PMID: 20739731 Tiessen RG, Lagerwey HJ, Jager GJ, Sprenger HG. Drug interaction caused by communication problems. Rhabdomyolysis due to a combination of itraconazole and simvastatin. Ned Tijdschr Geneeskd. 2010;154(14):A762. PMID: 20456775 van Wensen RJ, Bosscha K, Jager GJ, van der Linden JC, Fijnheer R. An invasive process in the pancreas: sometimes lymphoma. Ned Tijdschr Geneeskd. 2009;153:B164. PMID: 19818177 Hövels AM, Heesakkers RA, Adang EM, Barentsz JO, Jager GJ, Severens JL. Cost-effectiveness of MR lymphography for the detection of lymph node metastases in patients with prostate cancer. Radiology. 2009 Sep;252(3):729-36. PMID: 19717752

Ritchie ED, Jager GJ, van der Linden JC, Bosscha K. Three adults with intra-abdominal lymphangioma. Ned Tijdschr Geneeskd. 2009 Mar 7;153(10):456-9. PMID: 19374097 van Vugt R, Bosscha K, Olsman J, Jager GJ, de Jager CP. Management of hepatic trauma: a 9-year experience in ’s-Hertogenbosch. Acta Chir Belg. 2009 Jan-Feb;109(1):42-6. PMID: 19341194 Brink M, Kool DR, Dekker HM, Deunk J, Jager GJ, van Kuijk C, Edwards MJ, Blickman JG. Predictors of abnormal chest CT after blunt trauma: a critical appraisal of the literature. Clin Radiol. 2009 Mar;64(3):272-83. PMID: 19185657 Looij BG, Jager GJ, van Munster IP. An adult with lower abdominal pain. Neth J Med. 2008 Dec;66(11):495-6. PMID: 19075319 Koebrugge B, van Leuken M, Ernst MF, van Munster I, Bosscha K. Percutaneous Cholecystostomy in Critically Ill Patients with a Cholecystitis: A Safe Option. Dig Surg. 2010 Oct 15;27(5):417-421. PMID: 20948216

Heesakkers RA, Jager GJ, Hövels AM, de Hoop B, van den Bosch HC, Raat F, Witjes JA, Mulders PF, van der Kaa CH, Barentsz JO. Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran10-enhanced MR imaging. Radiology. 2009 May;251(2):408-14. PMID: 19401573

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Proefschriften

Boeken

Rutten MJ. Ultrasound of the shoulder. Efficacy studies. St. Radboud Universiteit Nijmegen, 15 juni 2010, Nijmegen.

Rutten MJ. Ultrasound of the shoulder. Efficacy studies. 15 juni 2010. ISBN: 978-90-9025418-0

Trefwoorden: Echografie, Schouder

Trefwoorden: Echografie, Schouder

Abstracts, voordrachten en posters Looij BG, Kreb DL, van der Linden JC, Ernst MF, Pruijt JFM, Bosscha K, Jager GJ, Rutten MJ. In vivo radio frequency ablation (RFA) in small breast cancer: Preliminairy results. ECR 2009, Oral presentation, Wenen, 6 maart 2009. Rutten MJ. Radiofrequentie ablatie van longtumoren: techniek en indicaties. Thema-avond IKZ-werkgroep longtumoren: ‘Nieuwste behandelingsmogelijkheden in de longoncologie’, Eindhoven, 16 juni 2009. Rutten MJ. “Shoulder US: my number one”. MSK Refresher Course Annual Meeting Radiological Society. “How to try not to be torn between ultrasound and MRI of the shoulder”. Radiologendagen 2009, Amsterdam, 18 september 2009. Rutten MJ. Shoulder Imaging. Symposium Radiologie voor sport fysiotherapeut. Nederland. Ede, 21 november 2009. Martinoli C, Genova, ITALY; Bouffard JA, Detroit, MI; Brandon CJ, Ann Arbor, MI; Cardinal E, Montreal, QC; Ceulemans RY, Chicago, IL; Craig JG, Ann Arbor, MI; Fessell DP, Ann Arbor, MI; Habra G, Troy, MI; Kislyakova M, Moscow, RUSSIAN FEDERATION; Introcaso JH, Northfield, IL; Jacobson JA, Ann Arbor, MI; Rutten MJ,

radiologie

’s-Hertogenbosch, NETHERLANDS; Van Holsbeeck MT, Detroit, MI; Wortsman XL, Santiago, CHILE; Lee KS, Marx MV. RSNA 96th Scientific assembly and annual Meeting. RSNA Refresher course: Musculoskeletal Ultrasound with focus on peripheral nerves: The Brachial plexus. Chicago, 1 december 2010. Cardinal E, Montreal, QC; Van Holsbeeck MT, Detroit, MI; Wortsman XL, Santiago, RM CHILE; Bouffard JA, Detroit, MI; Bureau NJ, Montreal, QC; Craig JG, Ann Arbor, MI; Ceulemans RY, Chicago, IL; Fessell DP, Ann Arbor, MI; Habra G, Troy, MI; Introcaso JH, Northfield, IL; Jacobson JA, Ann Arbor, MI; Martinoli C, Genova, ITALY; Rutten MJ, ’s-Hertogenbosch, NETHERLANDS; Khoury V, Montreal, QC; Lee KS, Marx MV. RSNA 96th Scientific assembly and annual Meeting. RSNA Refresher course: Dynamic Musculoskeletal Ultrasound of the upper extremity (Hands-on Workshop). Chicago, 2 december 2010. Martinoli C, Genova, ITALY; Bouffard JA, Detroit, MI; Brandon CJ, Ann Arbor, MI; Cardinal E, Montreal, QC; Ceulemans RY, Chicago, IL; Craig JG, Ann Arbor, MI; Fessell DP, Ann Arbor, MI; Habra G, Troy, MI; Kislyakova M, Moscow, RUSSIAN FEDERATION; Introcaso JH, Northfield, IL; Jacobson JA, Ann Arbor, MI; Rutten MJ, ’s-Hertogenbosch, NETHERLANDS; Van Holsbeeck MT, Detroit, MI; Wortsman XL, Santiago, CHILE; Lee KS, Marx MV. RSNA 95th Scientific assembly and annual Meeting. RSNA Refresher course: Musculoskeletal Ultrasound

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with focus on peripheral nerves: The Brachial plexus. Chicago, 2 december, Wen: 08:30 AM - 10:00 AM 2009.

Onderliggende techniek en scanmethode. Regionale refereeravond OOR Oost Nederland. Vught, 23 september 2010.

Cardinal E, Montreal, QC; Van Holsbeeck MT, Detroit, MI; Wortsman XL, Santiago, RM CHILE; Bouffard JA, Detroit, MI; Bureau NJ, Montreal, QC; Craig JG, Ann Arbor, MI; Ceulemans RY, Chicago, IL; Fessell DP, Ann Arbor, MI; Habra G, Troy, MI; Introcaso JH, Northfield, IL; Jacobson JA, Ann Arbor, MI; Martinoli C, Genova, ITALY; Rutten MJ, ’s-Hertogenbosch, NETHERLANDS; Khoury V, Montreal, QC; Lee KS, Marx MV. RSNA 95th Scientific assembly and annual Meeting. RSNA Refresher course: Dynamic Musculoskeletal Ultrasound of the upper extremity (Hands-on Workshop). Chicago, 3 december, Thu: 08:30 AM - 10:00 AM. 2009.

Fassaert T, de Jong M, Dubelaar I, Rutten MJ. Automated 3D Breast Volume Scanning. Voor- en nadelen. Regionale refereeravond OOR Oost Nederland. Vught, 23 september 2010.

Rutten MJ. Instabiele schouder: CT-, directe en indirecte MR-arthrografie SWC Skelet. Bijscholingscursus Nederlandse Vereninging voor Radiologie. Ede, 2 en 5 februari 2010. Rutten MJ. Ultrasound of the shoulder. Efficacy studies. Onderwijsdag OOR ZUID en Oost Nederland, Den Bosch, 23 april 2010. Rutten MJ. Musculoskeletal lesions: Mistakes you shouldn’t make. Interactive teaching session. Onderwijsdag OOR ZUID en Oost Nederland, Den Bosch, 23 april 2010. Rutten MJ. Ultrasound of the shoulder. Efficacy studies. Verdediging dissertatie aan Radboud University Nijmegen, 15 juni 2010. Dubelaar I, Fassaert T, de Jong M, Rutten MJ. Automated 3D Breast Volume Scanning.

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Fassaert T, de Jong M, Dubelaar I, Rutten MJ. Automated 3D Breast Volume Scanning. Echografische kenmerken van solide tumoren en eerste klinische ervaringen. Regionale refereeravond OOR Oost Nederland. Vught, 23 september 2010. Rutten MJ. Ultrasound of the shoulder. Efficacy studies. Werkgroep Deskundigheidsbevordering Sportgeneeskunde. UMCU: Opleidingen in de Sportgeneeskunde: Cursus gewricht: De schouder. Utrecht, 12 oktober 2010. Rutten MJ. Automated 3D Breast Volume Scanning. Siemens Usersday 2010. Groningen, 4 november 2010. Rutten MJ. Ultrasound of the shoulder. Efficacy studies. Siemens Usersday 2010. Groningen, 4 november 2010. Ranschaert ER. Online Radiology Resources: top 10 teaching websites and how to find them. ECR 2009, Vienna, Austria, 6-10 maart 2009. Ranschaert ER. Klinische ervaring met diffusie-MRI in het Jeroen Bosch Ziekenhuis. Symposium “Diffusie brengt MRI in beweging”, ’s-Hertogenbosch, 27 maart 2010.


Ranschaert ER. How Radiologists can use the Web as a tool to Enhance their Profession. http://www.isrvirtual.org/program/congisr_prog_2009.htm ISR 2nd Virtual Congress, 1-24 april 2009. Ranschaert ER, Deckers F. Diffusie-MRI van het abdomen, Sectiedag Abdominale Radiologie NVvR, Leiden, 8 mei 2010. Ranschaert ER. CT-colonografie, Siemens CT-userdag, Haarlem, 12 maart 2009. Ranschaert ER. Diffusie-MRI van het abdomen. Radiologendagen, Amsterdam, 17-18 september 2009.

Ranschaert ER CT-colonografie. Regionale nascholing MDL-artsen, Ravenstein, 27 januari 2009. Ranschaert ER. Is er nog een rol voor X-colon? Regionale nascholing MDL-artsen OOR-ON, ’s-Hertogenbosch, 8 Mei 2009. Ranschaert ER. CT colonografie: waar gaan we en waar staan we? 11e Bossche Gastro-enterologie Symposium, Vught, 5 februari 2009. Koebrugge B, Van Leuken M, Ernst MF, Van Munster I, Bosscha K. Percutane galblaasdrainage bij patiënten met een acute cholecystitis in slechte klinische toestand: een goede optie ?! Najaarsvergadering NVvH, Ede, 27 november 2009.

Publicaties (niet pubmed) Rutten MJ, Setz-Pels W, Hermens H, Franken R. Nieuwe CT-angiografie toepassing verkort borstreconstructie. Cura, jaargang 6, nr 3, dec 2009, blz 17.

Rutten MJ, de Jong MD, van Loon T, Jager GJ. Intratendinous ganglion of the long head of the biceps tendon: US and MRI features. European Radiology (2010). DOI 10.1007/s00330-010-1818-3.

Trefwoorden: borstreconstructie, CT-angiografie

Trefwoorden: Schouder, echografie

Hermens H, Franken R, Setz-Pels W, Rutten MJ. Opereren aan de hand van een landkaart. JBZ Palet, jaargang 5, nr 8, dec 2009. Trefwoorden: borstreconstructie, CT-angiografie

Spaargaren GJ, Rutten MJ. Bone infarct. Radiological Documents 2009; 27 (1): 1-3. JBR-BTR.

Setz-Pels W, Rutten MJ, Franken R, Hermens H. Jeroen Bosch Ziekenhuis gebruikt nieuwe methode bij borstreconstructie. Medicalfacts: 20 jan 2010, Thuis in het nieuws: 23 jan 2010, Brug Berlicum eo: 28 jan 2010.

Trefwoorden: Bot infarct, radiologische beeldvorming

Rutten MJ, Jager GJ, Kiemeney LA. Ultrasound detection of rotator cuff tears: observer agreement related to increasing experience. AJR 2010; 195:W440-W446 Trefwoorden: Schouderechografie, onderzoekers afhankelijkheid

Trefwoorden: borstreconstructie, CT-angiografie

radiologie

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Rutten MJ. De schouders eronder. De Gelderlander, 8 juni 2010.

mammadiagnostiek en screening Medical 2010; 50:16-17 Trefwoorden: borstkanker, 3D-echografie

Trefwoorden: Schouder, echografie

van den Horn G, Rutten MJ. Pilomactricoma or epithelioma of Malherbe. Radiological Documents 2009; 27 (2), case 10. JBR-BTR.

Rutten MJ, Mus RD. Automated Breast Volume Scanning. 3D echografie van de mammae. Siemens Whitepaper, september 2010 Trefwoorden: borstkanker, 3D-echografie

Trefwoorden: weke delen tumor, echografie

Crommentuyn R, Rutten MJ. Nieuwe opleiden biedt houvast. Medisch Contact 2010; 65 (27):1318-1321. Trefwoorden: Medische opleiding, vernieuwing Boon P, Rutten MJ. Nieuwe echografie scanner ontdekt eerder borsttumoren Telegraaf. 28 aug 2010

Rutten MJ, Mus RD. Automated Breast Volume Scanning. 3D Ultrasound of the Breast. Siemens Whitepaper, oktober 2010 Trefwoorden: borstkanker, 3D-echografie

Rutten MJ. 3D-echografie van de borsten. Financieel Dagblad, November 2010. Trefwoorden: borstkanker, 3D-echografie

Trefwoorden: borstkanker, 3D-echografie

Rutten MJ. Veelbelovende toekomst voor driedimensionale echografie. Brabants Dagblad, 18 september 2010, Heusdense Courant, 22 september 2010 Trefwoorden: borstkanker, 3D-echografie

Mus RD, Rutten MJ. Radboudziekenhuis: 3D-echo zoekt naar borsttumor De Gelderlander, dinsdag 05 oktober 2010. Trefwoorden: borstkanker, 3D-echografie

Mus RD, Rutten MJ. UMC St Radboud en Jeroen Bosch Ziekenhuis testen nieuw 3D-echoapparaat. Borstkankeronderzoek in drie dimensies. Nieuwsbank, 04-10-2010.

Rutten MJ, de Jong MD, van Loon T, Jager GJ. A rare Cause of a soft tissue mass at the shoulder (2010:9A). European Radiology (2010) 20 (9): 2305. DOI Trefwoorden: Schouder, echografie

M. Scholman, Rutten MJ Primeur: radiologie heeft nieuwe 3D echografie scanner. Intranet JBZ. 27 aug 2010. Trefwoorden: borstkanker, 3D-echografie

Ranschaert ER. Tele-educatie voor CT-colonoscopie. MemoRad 2009; 14(1): 26-28 Ranschaert ER, Jager G, CT-colonografie. Labcontact 2009.

Trefwoorden: borstkanker, 3D-echografie

Rutten MJ, Mus RD. 3D-echografie opent deuren voor efficiëntere

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De Jong MD, Fassaert TA, Ranschaert ER. Arrested pneumatization of the skulle base. Radiological documents. 2010 Sep 8.


23

REUMATOLOGIE Wetenschappelijke publicaties Hartkamp A, Geenen R, Godaert GL, Bijl M, Bijlsma JW, Derksen RH. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial. Ann Rheum Dis. 2010 Jun;69(6):1144-7. PMID: 19854713

Van Hulst LT, Creemers MC, Fransen J, Li LC, Grol R, Hulscher ME, van Riel PL. How to improve DAS28 use in daily clinical practice? A pilot study of a nurse-led intervention. Rheumatology (Oxford). 2010 Apr;49(4):741-8. PMID: 20083537 Trefwoorden: reumatoide arthritis, monitoring ziekte-activiteit

Van Koulil S, van Lankveld W, Kraaimaat FW, van Helmond T, Vedder A, van Hoorn H, Donders R, de Jong AJ, Haverman JF, Korff KJ, van Riel PL, Cats HA, Evers AW. Tailored cognitive-behavioral therapy and exercise training for high-risk patients with fibromyalgia. Arthritis Care Res (Hoboken). 2010 Oct;62(10):1377-85. PMID: 20521308

De Brouwer SJ, Kraaimaat FW, Sweep FC, Creemers MC, Radstake TR, van Laarhoven AI, van Riel PL, Evers AW. Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses. Arthritis Res Ther 2010;12(3):R89 PMID: 20478029 Trefwoorden: psychofysiologische stressrespons,

Kroft EB, Creemers MC, van den Hoogen FH Boezeman JB, de Jong EM. Effectiveness, side-effects and period of remission after treatment with methotrexate in localized scleroderma and related sclerotic skin diseases: an inception cohort study. Br J Dermatol. 2009;160:1075-82 PMID: 19210503

reumatologische ziekten

Trefwoorden: methotrexaat, sclerodermiforme huidbeelden

reumatologie

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Proefschriften

Boeken

Creemers MC. Co-promotor M. Flendrie. Titel dissertatie: Effectiveness and safety of TNFalpha-blocking therapy in patients with rheumatoid artrhitis. 2009.

Creemers MC. Hoofdstuk 4. Anti-TNF. In: Reumatologie protocollen handboek. Ed. M. Janssen, C.G.M. Kallenberg, PLCM van Riel. Academic Pharmaceutical Productions bv. 2009 Trefwoorden: biologicals, anti-TNF

Abstracts, voordrachten en posters Creemers MC. Klinische manifestaties van systemische vasculitis. PAOG Heijendaal, Nijmegen, april 2009. Creemers MC. Dermatologie binnen de reumatologie. Landelijke nascholing Nurse Practioners. Utrecht, oktober 2009.

Creemers MC. International course for rheumatologists and dermatologists ‘psoriasis and psoriatic arthritis’. Chairmen organising committee, speaker and trainer workshop. Nijmegen, september 2009 Creemers MC. Biologicals; pros and cons. (N)ERASS; out of the box thinking, Leiden, maart 2010

Creemers MC. Peers-to-peers bijeenkomst arthritis psoriatica. Eindhoven, februari 2010.

Publicaties (niet pubmed) de Smit OJ, van Vugt RM. Gestruikeld over een paaltje? Nederlands tijdschrift voor Reumatologie, september 2009 Trefwoorden: Reactieve artritis na HIV infectie.

Van Koulil S, van Lankveld W, Kraaimaat FW, van Helmond T, Vedder A, van Hoorn H, Donders R, de Jong AJ, Haverman J, Korff KJ, van Riel PL, Cats HA, Evers AW. Tailored Cognitive–Behavioral Therapy and Exercise Training for High-Risk Patients With Fibromyalgia. Arthritis Care & Research.Vol. 62, No. 10, October 2010, pp 1377–1385.

Creemers MC. Reumatoide Artritis: Inzichten, Strategien en vErwachtingen – de RAISE survey. Immunology Results Today Sept. 2009 Trefwoorden: reumatoide artritis, patientenverwachtingen Evers AW, van Burik A, van de Goor SS, Hoeve D, Kraaimaat FW, de Jong EM, Creemers MC, van de Kerkhof PC, van Riel PL. E-health behandelingen bij chronische lichamelijke aandoeningen: Het patiëntenperspectief. N T v Reum 2010 Trefwoorden : E-health, chronische ziekten

Trefwoorden: fibromyalgie, cognitieve gedragstherapie

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24

REVALIDATIE GENEESKUNDE Wetenschappelijke publicaties Meijer JW, Voerman GE, Santegoets KM, Geurts AC. Short-term effects and long-term use of a hybrid orthosis for neuromuscular electrical stimulation of the upper extremity in patients after chronic stroke. J Rehabil Med. 2009 Feb;41(3):157-61. PMID: 19229448 van Nes IJ, van der Linden S, Hendricks HT, van Kuijk AA, Rulkens M, Verhagen WI, Geurts AC. Is visuospatial hemineglect really a determinant of postural control following stroke? An acute-phase study. Neurorehabil Neural Repair. 2009 Jul-Aug;23(6):609-14. PMID: 19118129

revalidatiegeneeskunde

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SPOEDEISENDE GENEESKUNDE Wetenschappelijke publicaties Jaspers JW, Kuppens SM, van Zundert AA, de Wildt MJ. Vaginal stones in a 5 year old girl: a novel approach of removal. J. Pediatrics and Adolescent Gynaecology 2010 feb: 23(1):e23-5 PMID 19643641. Trefwoorden: vaginal stones.

Boeken Alkemada AJ, Caminda K, Slenter M. Coauteur: Vernooij CM. Zakboek Spoedeisende geneeskunde voor artsen op de SEH. Eerste editie. Uitgave van Bohn Stafleu van Loghum, Nederland, 2010. ISBN: 978 90 313 4260 0

Abstracts, voordrachten en posters Gafni A. Poster: Diagnostic value of the ECG in extreme hyperkalemia. A case report. 3rd Dutch Emergency Medicine Conference, Egmond aan zee, June 2009.

spoedeisende geneeskunde

Vreeburg ME, Vernooij CM, Segers MJ, Hammacher ER. Poster: Treatment of impacted greenstick forearm fractures in children using bandage therapy; a validation study. EUSEM congress, Stockholm, Sweden, October 2010.

119

Vissers E, de Jager CP, Kusters R, van GageldonkLafeber AB,Wever PC. Poster: Hypophosphatemia and prolonged length of hospital stay in seronegative PCR positive patients with early acute Q-fever. Najaarsvergadering NVMM/VIZ/BVIKM, Amsterdam, November 2010. Vissers E, van Bebber IP, de Jager CP. Poster: ‘Giant Kidney Stone’ as Surprising Cause of Acute Abdominal Pain. 4th Dutch Emergency Medicine Conference, Egmond aan zee, June 2010. Gresnigt FM, de Jager CP. Poster: When bacterial infection is suspected; Don’t forget procalcitonin! 4th Dutch Emergency Medicine Conference, Egmond aan zee, June 2010.

Gresnigt FM, Louwerse E, de Jager CP. Voordracht: Does reversal of oral anticoagulant therapy in patients with intracerebral hemorrhage improve clinical outcome? Mediterranean Emergency Medicine Conference, Valencia, Spain, September 2009. Jaspers JW, van Leuken MH, Duppen JH, de Jager CP. Poster: Acute painfull paraplegia: beware of aortic dissection. Fifth Mediterranean Emergency Medicine Congress, Valencia, Spain, sept 2009. Menapal K, Macken T, Korst M, Laheij R, de Jager CP. Poster: The relation between D-dimer level and radiographically proven pulmonary embolism. 4th Dutch Emergency Medicine Conference, Egmond aan zee, June 2010.

Gresnigt FM, Paling A. Voordracht: Procedural sedation and analgesia, Propofol-ketamine or propofol-fentanyl? 4th Dutch Emergency Medicine Conference, Egmond aan zee, June 2010. Gresnigt FM, Louwerse E, de Jager CP. Voordracht: Does reversal of oral anticoagulant therapy in patients with intracerebral hemorrhage improve clinical outcome? 3rd Dutch Emergency Medicine Conference, Egmond aan zee, June 2009.

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26 UROLOGIE

Wetenschappelijke publicaties Persoon MC, Scherpbier AJ, Oei SG, Meijerink WJ, Schijven MP, Schout B, Beerlage HP, Hendrikx AJ. Learning laparoscopy without patients Ned Tijdschr Geneeskd. 2009 Jan 17;153(3):60-2. PMID: 19235339 Van Poppel PC, Stehouwer CD, Beutler JJ, Korst MB, Beerlage HP, Hoogeveen EK. Hyperchloremic metabolic acidosis in a patient with an ureteroileostomy according to Bricker. Ned Tijdschr Geneeskd. 2009 May 23;153(21):1024-8. PMID: 19757757 Meijer RP, Gemen EF, van Onna IE, van der Linden JC, Beerlage HP, Kusters GC. The value of an artificial neural network in the decision-making for prostate biopsies. World J Urol. 2009 Oct;27(5):593-8. PMID: 19562346

Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Piérart M, Mauer ME, Collette L; EORTC Radiation Oncology Group and Genito-Urinary Tract Cancer Group. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009 Jun 11;360(24):2516-27. PMID: 19516032 Van Onna IE, Oddens JR, Kok ET, van Moorselaar RJ, Bosch JL, Battermann JJ. External beam radiation therapy followed by interstitial radiotherapy with iridium-192 for solitary bladder tumours: results of 111 treated patients. Eur Urol. 2009 Jul;56(1):113-21. PMID: 18722048

De Vries RR, Nieuwenhuijzen JA, van Tinteren H, Oddens JR, Visser O, van der Poel HG, Bex A, Meinhardt W, Horenblas S; Urological Working Group of the Amsterdam Comprehensive Cancer Center. Prostate-sparing cystectomy: long-term oncological results. BJU Int. 2009 Nov;104(9):1239-43. PMID: 19549261

urologie

121

Boeken Beerlage HP. Hoofdstuk : “Laparoscopische radicale prostatectomie” in Handboek prostaataandoeningen. onder redactie van prof. dr. T.A. Boon; prof. dr. J.L.H.R. Bosch De Tijdstroom, maart 2009.

Beerlage HP. Aanbevelingen laparoscopie in de urologie. Onder redactie van dr. J.P. van Basten en dr. H.P. Beerlage Najaar 2010

Abstracts, voordrachten en posters Schipper RA. Erectiele Disfunctie: Oorzaak & Behandeling. NVFB Voorjaarscongres Zadelpijn en ander mannenleed. Zwolle, 26-3-2010. Schipper RA. De geschiedenis van pompen, prikken, pillen en prothesen. Symposium Urologie Seks in de Oude Kijk in ’t Jat. Groningen, 11-9-2010. Schipper RA. Opleiding stomaverpleegkundigen. JBZ, 24-3-2009. Schipper RA. Huisartsen Nascholing Erectiele Disfunctie (BMC). Vught, 21-4-2009. Schipper RA. BPH voor huisartsen, bijscholing. ’s-Hertogenbosch, 13-10-2009. Schipper RA. Opleiding artsenbezoekers Lilly: “Wat doet een uroloog”. St. Michielsgestel, 7-1-2010. Schipper RA. Onderwijs arts-assistenten Geriatrie. CLZ, 4-3-2010.

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Jansonius, De Vylder A. Voordracht: Buccal Mucosa Urethraplastiek, onze ervaringen. Jeroen Bosch Ziekenhuis, ’s Hertogenbosch. NVU najaarsvergadering,Groningen, 13 november 2009. Schrier BPh. Laparoscopische Sacrocolpopexie. NVEC, april 2009 & 2010 Schrier BPh. Resultaten Argus male sling. AUA, april 2009 & 2010 Schrier BPh. Workshop Argus male sling JBZ, november 2009 & 2010 Beerlage HP. Complicatie registratie en zo….. NVEC congres, Amsterdam, 2 april 2009. Beerlage HP. Behandeling van UPJ-stenose. Verplichte AIOS cursus laparoscopie, RITME instituut Rotterdam, 3 juni 2009. Beerlage HP. Waarom maken mensen fouten Praktisch Workshop Laparoscopie, ’s-Hertogenbosch, 26 juni 2009.


Beerlage HP. Radicale prostatectomie; snijvlakken en leercurve. Update in Urology, Lunteren, 5 september 2009. Beerlage HP. Toekomstige ontwikkelingen in de laparoscopie. Cursus laparoscopie, Elancourt Parijs, 28 Oktober 2009. Beerlage HP. Assistentie, van laparoscopie naar robotchirurgie. Congres OK-assistenten, AVL, Amsterdam, 28 november 2009. Beerlage HP. Transurethrale resectie blaastumor (TURT). Upfront cursus, Catharina ZKHS, Eindhoven, 18 december 2009. Beerlage HP. Transurethrale Resectie Prostaat (TURP). Upfront cursus, Catharina ZKHS, Eindhoven, 18 december 2009. Beerlage HP. Radicale prostatectomie; snijvlakken en leercurve. Update in Urology revisited, Oosterbeek, 6 februari 2010. Beerlage HP. Robot geassisteerde prostatectomy; impact van conversie. NVEC congres, Amersfoort, 16 maart 2010. Beerlage HP. Leercurve bij radicale prostatectomie, welke benadering is de beste? NVEC congres, Amersfoort, 16 maart 2010. Ontwikkelingen in de laparoscopie. Verplichte AIOS cursus laparoscopie, Elancourt, Frankrijk, 13 april 2010.

urologie

Beerlage HP. Conversion. Advanced course on laparoscopic nephrectomy, European School of Urology, EAU congres, Barcelona, 19 april 2010. Beerlage HP. Critical view of safety in laparoscopic nephrectomy. Advanced course on laparoscopic nephrectomy, European School of Urology, EAU congres, Barcelona, 19 april 2010. Beerlage HP. Extraperitoneal access. Advanced course on laparoscopic nephrectomy, European School of Urology, EAU congres, Barcelona, 19 april 2010. Beerlage HP. Extraperitoneal safe control of renal pedicle. Advanced course on laparoscopic nephrectomy, European School of Urology, EAU congres, Barcelona, 19 april 2010. Beerlage HP. Haemostasis. Advanced course on laparoscopic nephrectomy, European School of Urology, EAU congres, Barcelona, 19 april 2010. Beerlage HP. (Robot) partial nephrectomy. Advanced course on laparoscopic nephrectomy, European School of Urology, EAU congres, Barcelona, 19 april 2010. Beerlage HP. Laparoscopisch knopen. Praktisch Workshop Laparoscopie, ’s-Hertogenbosch, 11 juni 2010. Oddens JR. (Laparoscopische) lymfeklierdissectie bij prostaatcarcinoom: Vinden we wel wat we zoeken?

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State of the art urology, Wolfheze, 6 februari 2009. Oddens JR. Quality control in Transurthral resection of bladder tumours (TURBT). EAU congress, Stockholm, 17 maart 2009. Oddens JR. Nut van een eenmalige instillatie bij het nietspierinvasief blaascarcinoom. Refereeravond urologie, UMCN Nijmegen, 9 april 2009. Oddens JR. Kwaliteit van TURT in relatie tot oncologische uitkomst. Decembersymposium Het blaascarcinoom van A tot Z, JBZ, ’s-Hertogenbosch, 4 december 2009.

Publicaties (niet pubmed) Bochove-Overgaauw DM, Gelders W, De Vylder AM. Routine biopsies in pediatric circumcision: (non) sense? Journal of Pediatric Urology, Volume 5,Issue 3,1 june 2009, Pages 178-180.

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De Vylder AM, Van der Horst HJ. Is de optimale leeftijd voor behandeling van een primaire niet ingedaalde testis nog altijd tussen het eerste en tweede levensjaar? Urologen Vademecum,jaargang 4 nr.5/oktober 2009.


27

ZIEKENHUISFARMACIE Wetenschappelijke publicaties Sleegers MJ, Beutler JJ, Hardon WJ, Berden JH, Verhave JC, Conemans JM, Hollander DA, Dautzenberg PL, Hoogeveen EK. Reversible rapidly progressive dementia with parkinsonism induced by valproate in a patient with systemic lupus erythematosus. J Am Geriatr Soc. 2010 Apr;58(4):799-801. PMID: 20398172

Schmeits PC, Péquériaux NC, van Geest-Daalderop JH, Ouwehand ME, Coremans AM, Hermans MH, Conemans JM. Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin. Neth J Med. 2009 Feb;67(2):76-8. PMID: 19299851

Schmeits PC, Hermans MH, van Geest-Daalderop JH, Poodt J, de Sauvage Nolting PR, Conemans JM. VKORC1 mutations in patients with partial resistance to phenprocoumon. Br J Haematol. 2010 Mar;148(6):955-7. PMID: 19961479

Van Puijenbroek EP, Conemans JM, Van Grootheest AC. Spontaneous ADR Reports as a Trigger for Pharmacogenetic Research: Experiences in the Netherlands. Drug Saf 2009;32(3):255-64. PMID: 19338383

Hermans MH, Poodt J, van Geest-Daalderop JH, Péquériaux NC, Conemans JM. Resistance to coumarin derivatives due to mutated vitamin-K enzyme. Ned Tijdschr Geneeskd. 2009;153:A691. PMID: 19857286

Van Puijenbroek E, Conemans JM, Van Grootheest K. Spontaneous reports and pharmacogenetics. The role of the pharmacovigilance centre. Drug Saf 2009;32:357-8. PMID: 19388726

Dautzenberg PL, van der Zande JA, Conemans JM, Rikkert MG. Off-label drug use on a Dutch geriatric ward. Int J Geriatr Psychiatry. 2009 Oct;24(10):1173-4. PMID: 19771542

ziekenhuisfarmacie

Derijks HJ, Janknegt R, Heerdink ER, De Koning GH, Krekels M, Looij, B-J, Egberts AC. Influence of antidepressants on glycaemic control in patients with diabetes mellitus: an open label comparative study. J Clin Psychopharmacol. 2009; 29(4): 405-8. PMID: 19593191

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Proefschriften Derijks HJ. Influence of antidepressants on glucose homeostasis. 11 november 2009. ISBN/EAN: 978-90-8559-564-9 Proefschrift digitaal te raadplegen op: http://igitur-archive. library.uu.nl/dissertations/2009-1019-200116/UUindex.html

Abstracts, voordrachten en posters Poodt J, Schmeits PC, Van Geest-Daalderop JH, Conemans JM, Hermans MH. Patients with partial resistance to acenocoumarol and phenprocoumon; screening the VKORC1 gene. Meeting on Molecular Diagnostics. Scheveningen, 2009. Conemans JM. Bewaking op bijwerkingen in de (ziekenhuis)apotheek. Lareb Bijwerkingendag. Utrecht, 2009. Derijks HJ. Influence of antidepressant use on glycemic control in patients with diabetes mellitus: an open-label comparative study. 9th Congress of the European

Association for Clinical Pharmacology and Therapeutics, Edinburgh, 12-15 July 2009. Derijks HJ. Invloed van antidepressiva op de glucosehuishouding Highlights Pharmacotherapy 2010, Utrecht, 16 December 2010. Derijks HJ. Farmacologische profielen van antidepressiva Kerstbijeenkomst Lareb 2010, Beesd, 21 December 2010 Deinum JT. Medicatieoverdracht: een regionale verantwoordelijkheid. Prisma symposium, Amersfoort, 26 januari 2010.

Publicaties (niet pubmed) Conemans JM, Eppenga W. De koppeling van de gegevens van klinisch-chemische laboratoria, apotheken en huisartsen. Wat kan de voorschrijver op dit gebied verwachten? Een nieuwe generatie medicatiebewaking. Labcontact 2009;10(28):3-4. Conemans JM, Péqueriaux N, de Boer M, Eppenga W. Wat moet de huisarts weten over orale anticoagulantia en de trombosedienst? Labcontact 2009;30:1-2. Derijks HJ, Heerdink ER, Janknegt R, De Koning GH,

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Olivier B, Loonen AJ, Egberts AC. Farmacologische profielen van antidepressiva. Pharm Weekbl 2010; 4(5): 79-85. Derijks HJ, Meyboom RH, Heerdink ER, De Koning, Janknegt R, Lindquist M, Egberts AC. Associatie tussen antidepressivagebruik en glucosedisregulatie bewijs op basis van bijwerkingenmelding. Pharm Weekbl 2009; 3(2): 22-27. Derijks HJ. Invloed van antidepressiva op de glucosehuishouding. Psyfar 2010; 5(3): 28-33


28

OVERIGE STAFDIENSTEN Verpleegkunde / kwaliteit van zorg Wetenschappelijke publicaties Schuurman JP, Schoonhoven L, Defloor T, van Engelshoven I, van Ramshorst B, Buskens E. Economic evaluation of pressure ulcer care: a cost minimization analysis of preventive strategies. Nurs Econ. 2009 Nov-Dec;27(6):390-400, 415. PMID: 20050490

overige stafdiensten

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29 DIVERSEN Proefschriften Van Wijk P. (Co-promotor Schneeberger PM) Improving the Management of Blood Exposure Accidents in The Netherlands, Radboud Universiteit Nijmegen, 18 november 2009. Rutten MJ. Ultrasound of the shoulder. Efficacy studies. St. Radboud Universiteit Nijmegen, 15 juni 2010, Nijmegen. Trefwoorden: Echografie, Schouder

Creemers MC. Titel dissertatie: Effectiveness and safety of TNFalpha-blocking therapy in patients with rheumatoid artrhitis. 2009. Derijks HJ. Influence of antidepressants on glucose homeostasis. 11 november 2009. ISBN/EAN: 978-90-8559-564-9 Proefschrift digitaal te raadplegen op: http://igiturarchive.library.uu.nl/dissertations/2009-1019-200116/ UUindex.html

diversen

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WETENSCHAPSMIDDAG 2009 Programma 5de Wetenschapsmiddag JBZ – 12 maart 2009 – aula GZG 15:00

Opening

15:05

eter de Jager, internist-intensivist P PROCALCITONIN KINETICS IN LEGIONELLA PNEUMOPHILA PNEUMONIA

15:20 Boukje Koebrugge, arts-assistent chirurgie DELIRIUM NA ABDOMINALE CHIRURGIE OP EEN CHIRURGISCHE AFDELING MET STANDAARD AANDACHT VOOR HET DELIRIUM: INCIDENTIE, RISICOFACTOREN EN UITKOMSTEN 15:35 Marjolein Mattheij, arts-assistent kindergeneeskunde OVERWEIGHT IN CHILDREN: WHAT DO DUTCH PEDIATRICIANS SEE AND DO? 15:50 Deirdre Bochove-Overgaauw, arts-assistent urologie ARGUS “ADJUSTABLE MALE SLING” VOOR STRESSINCONTINENTIE BIJ MANNEN 16:05 Ellen Schatorjé, arts-assistent kindergeneeskunde HYPERTRANSAMINASEMIE BIJ PEDIATRISCHE CROHN PATIËNTEN TIJDENS INITIËLE BEHANDELING MET ENTERALE VOEDING 16:20

Pauze

16:35 Janneke Bressers, arts-assistent geriatrie BESPREKEN VAN HET REANIMATIEBELEID OP EEN AFDELING GERIATRIE: DE ERVARING VAN PATIËNT EN FAMILIE 16:50 Maaike Kusters, arts-assistent kindergeneeskunde ANTISTOFRESPONS NA TETANUSVACCINATIE BIJ KINDEREN MET DOWNSYNDROOM 17:05 Dashti Faraj, arts-assistent chirurgie FIVE YEARS RESULTS OF INGUINAL HERNIA TREATMENT WITH THE PROLENE HERNIA SYSTEM: A RETROSPECTIVE ANALYSIS 17:20 Robert Laheij, arts-assistent interne geneeskunde THE ANTIBACTERIAL ACTIVITY OF HONEY AGAINST A HYPERVIRULENT CLOSTRIDIUM DIFFICILE STRAIN 17:35

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Borrel en prijsuitreiking


WETENSCHAPSMIDDAG 2010 Programma 6de Wetenschapsmiddag JBZ – 4 februari 2010 – aula GZG 15:00

Openingswoord Willy Spaan, Voorzitter Raad van Bestuur, Jeroen Bosch Ziekenhuis

15:15 Wietske Wester, arts-assistent geriatrie DE ROL VAN MRI ONDERZOEK IN HET DIAGNOSTISCH TRAJECT VAN DE OUDERE ALZHEIMER PATIËNT 15:30 Frank van Eijkeren, klinisch fysiotherapeut NORDIC WALKING IN PARKINSON’S DISEASE: IMPROVES WALKING SPEED BUT LEAVES STRIDE LENGTH UNCHANGED 15:45 Mischa Jager, arts-assistent medische microbiologie EVALUATION OF A DIAGNOSTIC ALGORITHM FOR ACUTE Q-FEVER IN AN OUTBREAK SETTING 16:00

eter Schmeits, biomedisch wetenschapper P VKORC1 - RESISTENT VOOR DE TROMBOSEDIENST

16:15 Maurits Barendrecht, arts-assistent urologie EFFECTEN VAN FAST-TRACK PROTOCOL NA EEN CYSTECTOMIE MET URINEDEVIATIE 16:30

Pauze

16:45 Willemijn Eppinga, ziekenhuisapotheker in opleiding MEDICATIEBEWAKING “NEXT GENERATION” 17:00 Boukje Koebrugge, arts-assistent chirurgie ACCURATESSE VAN TRANSRECTALE ECHOGRAFIE IN DE PREOPERATIEVE STADIERING VAN T1 RECTUM LESIES MOGELIJK GESCHIKT VOOR TRANSANALE ENDOSCOPISCHE MICROCHIRURGIE (TEM) 17:15 Linda Kampschreur, arts-assistent interne geneeskunde ACUTE Q-FEVER-RELATED MORTALITY IN THE NETHERLANDS 17:30 Eugenie Gemen, research analist THE VALUE OF AN ARTIFICIAL NEURAL NETWORK IN THE DECISION-MAKING FOR PROSTATE BIOPSIES 17:45

Borrel en prijsuitreiking

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Wetenschappelijk onderzoek: hoe en waarom?

Dr. Mirrian Hilbink werkt als klinisch epidemioloog bij het wetenschapsbureau van het Jeroen Bosch Ziekenhuis. Zij helpt medisch specialisten, paramedici, analisten, arts-assistenten en verpleegkundigen bij het opzetten van onderzoek en bij het verzamelen, verwerken en analyseren van onderzoeksgegevens. Ze vertelt enthousiast over het belang hiervan. “Het wetenschapsbureau heeft als belangrijkste taak wetenschappelijk onderzoek binnen het Jeroen Bosch Ziekenhuis (JBZ) zoveel mogelijk te ondersteunen”, vertelt Hilbink. “Ik ben uitermate geïnteresseerd in onderzoek binnen een ziekenhuis. Zo denk ik vaak mee over bijvoorbeeld de onderzoeksvragen, uitvoeringsmethoden en analyses. De onderzoeken zijn boeiend, praktisch en zeer divers van aard. Ook begeleid ik vaker het opzetten van postermateriaal voor congressen of het schrijven van wetenschappelijke publicaties. Ik werk twee dagen per week in dit ziekenhuis. De overige tijd doe ik onderzoek in het Universitair Medisch Centrum St Radboud in Nijmegen.”

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Werkwijze Hilbink licht kort toe hoe ze te werk gaat: “Vaak krijg ik eerst een mailtje van een collega met een vraag over het doen van patiëntonderzoek. Dan ga ik met diegene in gesprek om na te denken over de onderzoeksvraag, het bepalen van de juiste onderzoeksopzet of geschikte analysetechniek. Ik heb graag dat mensen mij vroegtijdig bij hun onderzoek betrekken zodat we samen na kunnen denken over een opzet die valide en betrouwbare onderzoeksresultaten oplevert. Daarnaast is onderzoek vaak aan regels gebonden. Dit vanwege de patiëntveiligheid. Het is uitermate belangrijk dat de patiënten die meedoen geen schade oplopen door het onderzoek.” Advies op maat “Na het verzamelen van de onderzoeksgegevens begint het echte werk”, lacht Hilbink. “Namelijk het analyseren van de data en het beschrijven van de onderzoeksresultaten. Dat is mijns inziens het leukste onderdeel van het doen van onderzoek. De resultaten moeten altijd zorgvuldig en begrijpelijk opgeschreven worden: geven de figuren en tabellen het juiste beeld? Klopt de structuur? En zijn de conclusies juist en helder verwoord? Ik lever als het ware advies op maat. Dit is afhankelijk van de wensen en behoeften van de betreffende collega.” Visie Hilbink heeft een duidelijke visie voor ogen: “Binnen het JBZ is het aantal initiatieven voor het doen van onderzoek groot. Alleen publiceren we er nog te weinig over. Dat is jammer! Ook loopt een onderzoek nog wel eens vast in een vroeg stadium. Ik kan helpen om dat te voorkomen.” Tot slot benadrukt Hilbink nog een belangrijk punt: “Niet alleen in academische, maar ook in perifere ziekenhuizen, zoals het JBZ, is het doen van onderzoek belangrijk. De patiëntenpopulatie van perifere ziekenhuizen leent zich hier uitstekend voor. Mijns inziens is het essentieel om bij te dragen aan het verbeteren van de patiëntenzorg. Ik wil mensen hier graag bij helpen. Niet alleen individuele verzoeken, maar ik ga ook binnenkort intern scholingsbijeenkomsten geven.” Meer informatie Wilt u meer weten over dit onderwerp? Of heeft u vragen over het opzetten of uitvoeren van wetenschappelijk patiëntenonderzoek? Neem dan contact op met epidemioloog dr. Mirrian Hilbink via tel.: (073) 699 2970 of e-mail [email protected]. Zij werkt op woensdag en vrijdag bij het wetenschapsbureau van het Jeroen Bosch Ziekenhuis.

interview mirrian hilbink

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1. De rol van mri onderzoek in het diagnostisch traject van de oudere alzheimer patiënt 1. W.N. Wester1, M.D. Beutick1, P. Scheltens2, R.J. van Marum1, P.L.J. Dautzenberg1 Klinische geriatrie, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch, 2Afdeling neurologie, VU, Amsterdam

1

Achtergrond Vanuit de huidige Richtlijn diagnostiek en medicamenteuze behandeling van dementie (2005) wordt beeldvormend onderzoek van de hersenen aanbevolen bij patiënten jonger dan 65 jaar, bij iedere patiënt met klinische verdenking op een neurochirurgisch behandelbare aandoening en indien er meer zekerheid verlangd wordt omtrent de oorzaak van de cognitieve stoornis. Hieruit volgt dat op de afdeling geriatrie en op het geheugencentrum Jeroen Bosch Ziekenhuis niet bij iedereen met verdenking dementie beeldvormend onderzoek plaats heeft en er protocollair gestart wordt met een cholinesterase remmer bij de ziekte van Alzheimer en Lewy Body dementie en gestart wordt met preventieve maatregelen bij de klinische verdenking op Vasculaire dementie. In andere centra, zoals het academisch ziekenhuis de VU, vindt wel bij iedereen met cognitieve klachten beeldvormend onderzoek van de hersenen plaats. In de VU zullen door deze wijze ook weinig specifieke zeldzame aandoeningen minder worden gemist. De vraag is of de werkwijze van de afdeling geriatrie van het Jeroen Bosch Ziekenhuis, voortkomend uit de huidige Richtlijn patiënten tekort doet. De onderzoeksvraag is als volgt geformuleerd: leidt aanvullend MRI-cerebrum onderzoek bij patiënten >75jaar, tot verandering van reeds gestelde diagnose en/of reeds voorgenomen beleid als daar klinisch geen argumenten voor zijn? Methode Het betreft een prospectief, gerandomiseerd onderzoek. Van december 2008 tot november 2009 werden patiënten gerekruteerd van de poliklinieken en afdeling klinische geriatrie van het JBZ. Inclusiecriteria waren leeftijd >75 en, op grond van anamnese, lichamelijk onderzoek en beperkt NPO, multidisciplinair vast gesteld geen noodzaak tot aanvullend MRI cerebrum onderzoek. De interventiegroep onderging alsnog een MRI cerebrum. De controle groep is prospectief vervolgd om veranderingen in behandeling zonder MRI cerebrum te kunnen vervolgen. Patiënten die 2 jaar voorafgaand aan dit onderzoek MRI-c hadden ondergaan zijn geëxcludeerd. De MRI’s werden verslagen en beoordeeld door prof. dr. Ph, Scheltens, hoogleraar cognitieve neurologie aan het VU medisch centrum. Naar aanleiding van criteria volgens consensus in huidige literatuur werd de eerder gestelde diagnose heroverwogen en eventueel bijgesteld. Voorlopige resultaten Er werden in totaal 48 patiënten bereid gevonden te participeren in de controle en de interventiegroep. Gemiddelde leeftijd in de interventie groep was 82,8 jaar, variërend van 77-95 jaar. Ten tijde van deze wetenschapsmiddag zijn 16 van de 24 MRI’s officieel verslagen, waarbij vooralsnog geen diagnose wijzigingen zijn opgetreden. Voorlopige conclusie Voor alsnog is er geen diagnose of behandeling gewijzigd. Echter, vanwege de incomplete data op dit moment, is het nog te vroeg om onze onderzoeksvraag gefundeerd te beantwoorden. Wel bleek het erg lastig om voldoende patiënten te includeren in de interventiegroep. Blijkbaar worden aanvullende onderzoeken als overmatig belastend bevonden, hetgeen als secundaire overweging zeker meegenomen dient te worden in de beslissing omtrent aanvullend onderzoek in een kwetsbare oudere populatie.

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2. Nordic walking in parkinson’s disease: improves walking speed but leaves stride length unchanged Frank J.M. van Eijkeren1 Ruud S.J. Reijmers1 Mirjam J. Kleinveld1 Angret Minten1 Jan Pieter ter Bruggen1, Bastiaan R. Bloem2 1

Department of Neurology, Jeroen Bosch Hospital, ’s-Hertogenbosch, The Netherlands, 2Parkinson Center Nijmegen

(ParC), Department of Neurology, Donders Center for Neuroscience, Radboud University Nijmegen Medical Center, The Netherlands Objective Does a Nordic Walking-training program improve motor skills and walking condition in patients with Parkinson’s disease (PD)? What is the effect of this training on stride length? Methods We included 23 patients with PD. (16 men; mean age 64 years; range 48-78; disease severity Hoehn Yahr mean stage 2, range 1-3). Patients were trained for 6 weeks, with a frequency of twice a week. Patients were tested at baseline and immediately after the complete training program. Outcome measures included: the Timed 10-meter maximum walking speed (10 M Walk), the Timed Get Up and Go Test (TUG), the 6 minutes walking test (6 Min Walk), the number of steps as measured with the Runner FM05B step indicator (STEPS), stride length in meters (Stride Length) and the Parkinson Disease Quality of life questionnaire (PDQ-39). Results After training, the 10 M Walk, TUG, 6 Min Walk and the STEPS had improved significantly compared to baseline. Stride length and the PDQ-39 had not changed significantly. Conclusion After a six-week Nordic Walking training program, mildly affected IPD patients were able to improve their walking speed. The improved walking speed could not be attributed to an increased stride length, but rather to an increased movement frequency of the legs. Controlled studies are now justified to identify the intrinsic treatment effects, why especially bradykinesia has been changed and to determine how clinically meaningful these improvements are.

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3. Evaluation of a diagnostic algorithm for acute q-fever in an outbreak setting Mischa M. Jager1, Ineke Weers-Pothoff1, Mirjam H.A. Hermans2, Jeroen J.A. Schellekens2, Jamie C.E. Meekelenkamp1, Peter M. Schneeberger1, Peter C. Wever1 1

Department of Medical Microbiology and Infection Control, 2Molecular Diagnostics, Jeroen Bosch Ziekenhuis,

’s-Hertogenbosch Objectives An outbreak of Q-fever with over 3300 notified cases is ongoing in the Netherlands. Since 2007, immunofluorescence assay (IFA) has been the cornerstone of Q-fever serology in our hospital. IFA, however, is time-consuming and subject to inter-observer variability. Furthermore, the lag phase in antibody response to Coxiella burnetii renders serology less suitable for diagnosing early disease. Alternative diagnostic approaches include an ELISA for IgM phase II antibodies as screening assay (M II screen). In addition, IS1111 PCR on serum samples is capable of diagnosing acute Q-fever before antibodies appear. In 2009, we introduced a diagnostic algorithm (figure) for acute Q-fever with the M II screen as initial step. Subsequently, IFA and/or PCR were performed depending on outcome of M II screen, date of onset of disease and inpatient or outpatient setting. When diagnostics were inconclusive a 14-day follow-up serum sample was requested. Here, we evaluated the value of the algorithm in an outbreak setting. Methods We retrospectively evaluated outcome of Q-fever diagnostics according to the new algorithm in all patients referred between May 15th and 31st, 2009, with date of onset of disease unknown or < 3 months. Results In the 17-day period, 825 patients were tested. The diagnosis acute Q-fever was made in 256 patients (31%) - in 197 patients on the first serum sample, in 59 patients on the 14-day follow-up serum sample. A negative M II screen was obtained in 669/825 first serum samples resulting in reduction of IFAs performed by more than 80%. Ninety-two M II screen negative patients were diagnosed with acute Q-fever by positive PCR. Cross-reactivity was documented in 4% of patients with a positive M II screen. Almost 50% of physicians did not list date of onset of disease. Requested follow-up serum samples were not received from 306 patients leading to inconclusive outcomes. Conclusion Introduction of the M II screen significantly reduced the number of IFAs performed, while introduction of PCR allowed for diagnosis of acute Q-fever in a substantial number of seronegative patients. Pitfalls to the presented algorithm are the poor communication by many physicians of the first day of disease, which is a critical component in the algorithm, and the suboptimal response to requests for follow-up serum samples implying that cases of acute Q-fever might have been missed.

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ELISA M2 screen

positive /

negative

doubtful

positive:

first day of

acute

symptoms:

Q-fever

≤ 14 days or applicant is specialist and unknown day of first symptoms

IFA G

PCR

and M negative: request for

at least M2

follow-up

and G2

acute Q-fever

positive first day of symptoms

no Q-fever

> 14 days

past or

only G

chronic

positive

infection positive: acute Q-fever

applicant general practitioner

request for

and unknown

follow-up

first day of symptoms

other

PCR

negative: request for follow-up

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4. Vkorc1 - resistent voor de trombosedienst Peter C. Schmeits1, Jeroen Poodt2, Mirjam H.A. Hermans2, Nathalie C. Péquériaux3, Jean M. Conemans1 1

Ziekenhuisapotheek Noordoost-Brabant’, ’s-Hertogenbosch, 2Moleculaire Diagnostiek, 3Laboratorium voor Klinische Chemie

en Hematologie, Jeroen Bosch Ziekenhuis,’s-Hertogenbosch In 2006 stond er een casus in het Nederlands Tijdschrift voor de Geneeskunde van een 78-jarige man die niet ingesteld kon worden op zijn antistollingsmedicatie. Eerst was hem acenocoumarol voorgeschreven; wegens onvoldoende effect werd overgeschakeld op fenprocoumon. De maat van antistolling wordt weergegeven in een INR waarde. Een normale antistolling heeft een INR (International Normalised Ratio) van 1. Patiënten die ontstold moeten worden, hebben een streefgebied waar de INR tussen moet liggen. Dit streefgebied is meestal tussen de 2,5 en de 4,0. Bij de beschreven patiënt kon nauwelijks een INR-verhoging worden bereikt. De auteurs suggereerden dat de oorzaak een genetische resistentie kon zijn in het VKORC1 (Vitamine K-epoxidereductasecomplex subunit 1) gen. Dit gen codeert voor het eiwit VKOR, het sleutelenzym in de vitamineK-pomp. Coumarines interacteren met dit eiwit. Afwijkingen in het VKORC1 gen kunnen de oorzaak zijn van therapiefalen. Wij zochten contact met de auteurs en vroegen een buis bloed op van de patiënt. Deze patiënt bleek een afwijking te hebben die zorgde voor een aminozuurverandering met als code Trp59Arg. De Tryptofaan op de 59e plaats van het eiwit was vervangen door een Arginine. Deze variant werd niet eerder beschreven in de literatuur. Bij het aanbieden van de bevindingen aan een internationaal tijdschrift kwamen de reviewers met twee belangrijke vragen. 1) Komt deze variant nog meer voor bij mensen met therapiefalen? 2) Komt deze variant niet voor bij patiënten die normaal reageren op hun medicatie? Om dit uit te zoeken hebben we in het hele land bloedmonsters opgevraagd van patiënten die niet op coumarines reageerden. Dit leverde 10 monsters op waarvan er 2 een genetische afwijking toonden in het VKORC1 gen. Bij 1 patiënt werd de Trp59Arg mutatie gevonden, bij een andere patiënt werd een andere nieuwe mutatie gevonden: Ser52Leu, de inbouw van een Leucine in plaats van een Serine op aminozuur 52 van het eiwit. Bij de overige 8 patiënten had de lastige instelbaarheid een andere oorzaak (non-adherence, interacties). Daarnaast werden 100 anonieme controles verkregen van de trombosedienst. Geen van deze 100 monsters bezat één van de bovengenoemde genetische afwijkingen in het VKORC1 gen. Tijdens het schrijven van een artikel om de resultaten te publiceren ontvingen we een aanvraag van nog een patiënt. Ook deze patiënt bezat de Trp59Arg mutatie. Bij patiënten die niet in te stellen zijn op antistollingsmedicatie wordt eerst een aantal zaken nagekeken, waaronder geneesmiddeleninteracties en therapietrouw. Wanneer alle mogelijkheden zijn uitgesloten wordt de serumconcentratie van het coumarine bepaald. Bij een hoge concentratie met tegelijk een erg lage INR wordt al veel duidelijk. Ter confirmatie wordt de genetica nagekeken. Wanneer een genetische variant wordt gevonden betekent dit veel voor de patiënt en zijn behandelaar. Het belangrijkste is duidelijkheid. Er hangt altijd een geur van therapieontrouw over een patiënt wanneer deze niet is in te stellen. Wanneer wordt aangetoond dat de oorzaak in zijn/haar genen zit, zorgt dat voor veel opluchting. De therapie wordt vervolgd door de antistollingsmedicatie verder op te hogen tot een dosis die levensgevaarlijk zou zijn bij patiënten zonder genetische resistentie. Inmiddels hebben wij 5 patiënten geïdentificeerd met een dergelijke genetische “warfarine-resistentie.” Wij vonden bij hen dus 2 genetische varianten die beide niet eerder in de literatuur werden beschreven. Tenslotte formuleerden wij een algoritme voor het Netherlands Journal of Medicine voor de onbegrepen INR, waar de besproken coumarine-resistentie een -bescheiden- plaats in kreeg.

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5. Effecten van fast-track protocol na een cystectomie met urinedeviatie Maurits Barendrecht, Jorg R. Oddens Afdeling Urologie, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch Introductie In de postoperatieve fase na een cystectomie met aanleg van een urine deviatie (ileo-uretero-cutaneostomie volgens Bricker of dundarm-neoblaas) wordt regelmatig een postoperatieve ileus (tot dag 4 post-operatief ontbreken van darm peristaltiek) als complicatie gezien. Het Fast-Track protocol volgens ERAS (Enhanced Recovery After Surgery) heeft het aantal complicaties, waaronder de postoperatieve ileus, bij verschillende vormen van colon-chirurgie verminderd. Echter, deze vorm van peri-operatieve zorg is bij een cystectomie relatief onbekend. In deze studie is gekeken naar de effecten van het invoeren van het Fast-Track protocol na een cystectomie met urinedeviatie. Methode Een retrospectieve analyse is verricht van de cystectomiën over de periode 2006 t/m 2009 bij patiënten van de afdeling urologie in het Jeroen Bosch Ziekenhuis . Traditionele peri-operatieve zorg in het jaar 2006 en 2007 is vergeleken met de jaren 2008 en 2009 waarin het Fast-Track protocol is toegepast. De uitkomstmaten voor deze vergelijking zijn het optreden van een postoperatieve ileus en de gemiddelde opnameduur. Daarnaast zijn patiëntkarakteristieken, indicatie, per-operatieve gegevens, pathologische verslagen en follow-up geanalyseerd. Resultaten In 2006-2007 en 2008-2009 werden door 3 operateurs respectievelijk 27 en 30 (n totaal = 57) cystectomiën uitgevoerd. Gemiddelde leeftijd, geslachtsverhouding, en per-operatieve parameters verschilden niet tussen de groepen. De gemiddelde opnameduur in de traditionele behandelingsgroep en Fast-Track groep was 20,4 ± s.d. 7,8 en 17,0 ± s.d. 6,9 dagen respectievelijk (p = 0.08). De postoperatieve complicatie ileus kwam in de Fast-Track groep minder voor dan in de traditionele groep (13% vs 19%) echter statistisch niet significant. Conclusie Het Fast-Track protocol volgens ERAS bij de cystectomie met aanleg urinedeviatie in deze retrospectieve studie lijkt tot een daling van het aantal patiënten met een postoperatieve ileus te leiden. Gekoppeld aan deze bevinding is een dalende trend waarneembaar in de gemiddelde opnameduur.

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6. Medicatiebewaking ‘next generation’ Willemijn L. Eppenga, Jean M.H. Conemans Ziekenhuisapotheek Noordoost-Brabant’, ’s-Hertogenbosch, Inleiding Het HARM-wrestling rapport heeft veel stof doen opwaaien. Maar liefst 19.000 medicatiegerelateerde ziekenhuisopnames per jaar zijn onnodig. Het HARM-wrestlingrapport geeft gedetailleerde aanbevelingen om bijwerking-gerelateerde ziekenhuisopnames te reduceren. De suggesties zijn zowel inhoudelijk als organisatorisch. Eén van de aanbevelingen (aanbeveling 1e) betreft ondersteuning door ICT. Aanbeveling 1(e): Het benutten van nieuwe ICT mogelijkheden, zoals het raadplegen en toepassen van elektronische patiëntgegevens via koppelingen tussen de computersystemen van zorgprofessionals en zorginstellingen in de eerste en tweede lijn. Het aanbod aan software die medicatiegegevens kan combineren met laboratoriumuitslagen is beperkt. Ziekenhuisapotheek Noordoost-Brabant heeft daarom in samenwerking met de bedrijven Inforay en Emotional Brain Pharmaps® Medicatiebewaking PLUS ontwikkeld. Dit is een intelligent medicatiebewakingssysteem dat webbased fungeert, onafhankelijk van andere software. Met intelligent wordt bedoeld dat met redeneerregels alleen de echt relevante signalen met betrekking tot geneesmiddelen zichtbaar gemaakt worden. Om te laten zien dat het nieuwe systeem Pharmaps daadwerkelijk beter is dan het huidige systeem Centrasys is als eerste onderzoeksvraag het volgende geformuleerd: “Hoe verhouden de sensitiviteit, specificiteit en positief voorspellende waarde van verschillende versies van Pharmaps® zich tot die van verschillende versies van Centrasys (“nieuwe” versus “oude” medicatiebewaking)? Een voorbeeld van medicatiebewaking nieuwe stijl is de geautomatiseerde bewaking van de dosering door toetsing aan de kreatinineklaring bij renaal geklaarde geneesmiddelen. Onderzoeksopzet Er wordt op dit moment een vergelijkend observationeel onderzoek uitgevoerd, waarbij de performance van 6 verschillende versies van 2 medicatiebewakingssystemen met elkaar vergeleken worden. Hiervoor worden ongeveer 2000 medicatieopdrachten gebruikt. Om een goed beeld te krijgen moeten minimaal 400 medicatiebewakingsignalen beoordeeld worden. De studie vindt plaats in het Jeroen Bosch Ziekenhuis. Deze studie wordt uitgevoerd op 3 afdelingen van het Jeroen Bosch ziekenhuis, te weten cardiologie, orthopedie en geriatrie. Door te kiezen voor drie verschillende afdelingen wordt gedacht een brede variëteit aan medicatiebewakingsignalen te observeren. Zo wordt de performance van de systemen op verschillende vlakken bekeken. Het JBZ gebruikt Centrasys. Het EVS van iSoft is sinds 2007 operationeel in het Jeroen Bosch ziekenhuis. Voorschrijvers krijgen een beperkt aantal medicatiebewakingsignalen te zienen de ziekenhuisapotheker controleert aan het eind van de dag nog de overige medicatiebewakingsignalen.. Discussie Het onderzoek is momenteel in volle gang. De resultaten zullen voor de zomer bekend zijn. Pharmaps® Medicatiebewaking Plus is nog volop in ontwikkeling. Na uitvoering van deze studie en een validatietraject met de gewenste uitkomst zal Pharmaps® Medicatiebewaking Plus geïmplementeerd worden in de ziekenhuisapotheek. Tevens zijn er gesprekken met Alert® om Pharmaps® Medicatiebewaking Plus te integreren. Het is evident dat door het combineren van individuele laboratoriumgegevens van een patiënt met zijn/haar medicatiegegevens leidt tot medicatiebewakingsignalen toegespitst op de specifieke patiënt. Naast de individuele farmacotherapie is er nu ook een weg ingeslagen om de medicatiebewaking van deze farmacotherapie te individualiseren en optimaliseren. Het gaat om een systeem dat nu transmuraal functioneert. De medicatiebewakingsignalen komen nu nog in de ziekenhuisapotheek of stadsapotheek terecht. In de toekomst lijkt het zinvol om de signalen te presenteren op moment van voorschrijven (clinical decision support). Voor het formuleren van farmacotherapeutisch beleid en van medicatieprotocollen zal een beroep gedaan worden op ervaren clinici.

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7. Accuratesse van transrectale echografie in de preoperatieve stadiering van rectum lesies mogelijk geschikt voor transanale endoscopische microchirurgie (tem) Boukje Koebrugge1, Koop Bosscha1, Gerrit Jager2, Miranda Ernst1 1

Afdeling Chirurgie, 2 Afd. Radiologie, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch

Achtergrond De Transanale Endoscopische Microchirurgie (TEM) is een minimaal invasieve techniek voor de locale resectie van benigne adenomen en stadium T1 rectum carcinomen in geselecteerde patiënten, gepaard gaande met lagere morbiditeit en mortaliteit dan conventionele open chirurgie. Transrectale Echografie is een belangrijk diagnosticum ter preoperatieve stadiëring van deze rectumlaesies. Het doel van de studie was het bepalen van de accuratesse van preoperatieve transrectale echografie bij rectumlaesies, mogelijk geschikt voor TEM. Methode Sinds 2006 ondergaan alle patiënten mogelijk geschikt voor TEM transrectale echografie als onderdeel van de preoperatieve T-stadiering. De belangrijkste vraag was of de muscularis propria was onderbroken (scheidingsvlak T1-T2 laesies). Naar aanleiding van de stadiëring middels transrectale echografie werd respectievelijk een TEM uitgevoerd of aanvullende diagnostiek vervaardigd (MRI rectum). Preoperatieve echografische bevindingen werden vergeleken met de postoperatieve pathologische stadiering. Resultaten 36 patiënten met rectale laesies met een gemiddelde leeftijd van 66 jaar werden geïncludeerd. Bij 30 patiënten was de transrectale echografie conclusief en toonde 28 T0/T1 laesies waarbij een TEM werd vervaardigd, 1 T2 carcinoom (bevestigd middels een MRI rectum) waarbij een Low Anterior Resectie werd vervaardigd en 1 T3 carcinoom (mogelijk artefact bevinding na eerdere biopsie). Na MRI werd bij deze patiënt alsnog een TEM uitgevoerd. Postoperatieve stadiëring bevestigde de preoperatieve echografische bevindingen bij 29/30 patiënten. De T3 laesie bleek inderdaad een eerder gebiopteerde T0 laesie te zijn. Er vond geen onderstadiëring plaats. De accuratesse in deze groep was 97%. Bij 6 patiënten was de transrectale echografie niet conclusief; bij 4 patiënten werd aanvullende diagnostiek verricht middels een MRI, waarbij in geen van de 4 patiënten tumorinvasie werd gezien. Bij 5 van de 6 patiënten werd alsnog een TEM uitgevoerd. Bij 2 patiënten werd deze geconverteerd naar een Low Anterior Resectie in verband met localisatie/grootte van de tumor. Postoperatieve stadiëring toonde 5 adenomen. Bij 1 patiënt werd geen chirurgische ingreep uitgevoerd, omdat er geen tumor zichtbaar was op MRI. Stadiering van de rectale laesie middels Transrectale echografie was mogelijk bij 30/36 patiënten (83%). Overall accuratesse van transrectale echografie in de preoperatieve stadiëring van rectumlaesies mogelijk geschikt voor TEM was 80%. Accuratesse in de conclusieve groep was echter 97%. Conclusie Transrectale echografie is een goed diagnostisch middel om preoperatief T0/T1 laesies geschikt voor TEM te onderscheiden van rectum laesies met invasie van de muscularis propria; een indicatie voor radicale chirurgie. Als Transrectale echografie niet conclusief is of een hoog stadium rectum laesie (>T2) toont, dan is aanvullende diagnostiek (MRI rectum) geïndiceerd.

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8. Acute q-fever-related mortality in the Netherlands(tem) L.M. Kampschreur1, M.C.A. Wegdam-Blans2, S.F.T. Thijsen3, C.A.R. Groot4, P.M. Schneeberger5, W.L. van Eede6, F.S. Stals7, A.A.M.J. Hollander1, J.H.E.M. Schijen8, N.L.A. Arents2, P.C. Wever5 Dept. of Internal Medicine, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch, 2Regional Laboratory for Medical Microbiology, St.

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PAMM, Veldhoven, 3Dept. of Microbiology, Diakonessenhuis Utrecht, Utrecht, 4Dept. of Pulmonology, Bernhoven Hospital, Oss, Department of Medical Microbiology and Infection Control, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch, 6Dept. of Intensive Care

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Medicine, Diakonessenhuis Utrecht, Utrecht, 7Atrium Medisch Centrum Parkstad, Heerlen, 8St. Elisabeth Hospital, Tilburg, The Netherlands A large outbreak of Q-fever with over 3300 cases since 2007 has been reported in the Netherlands. Available date indicate that approximately 700 patients have been hospitalized with acute Q-fever. Reported mortality rates in hospitalized patients with acute Q-fever range from 0.9 to 2.4%. Here, we analyzed mortality among hospitalized patients with acute Q-fever. Death resulting from chronic Q-fever was not evaluated. Clinicians and microbiologists from hospitals in the afflicted region were asked to provide details about patients who had died after diagnosis of acute Q-fever. Eight patients (7 males, 1 female) from 6 hospitals were identified who died in approximately one month following hospitalization with acute Q-fever. Diagnosis was made by PCR only (4x), serology only (2x) or both (2x). Six patients presented with infiltrative changes on the X-thorax and a median CURB-65 score of 3 (range 1-3). Median age at time of death was 76 years (range 55-86). Median time of hospitalization was 13 days (range 1-33). All patients had serious, often coinciding, underlying conditions including chronic cardiovascular disease (6x), chronic lung disease (5x), diabetes mellitus (3x) or malignancy (2x). Thus, we found a mortality rate around 1% among patients hospitalized with acute Q-fever in the Netherlands. All patients had serious underlying conditions. It cannot be excluded that death to acute Q-fever is underreported for instance because in many hospitals PCR for Q-fever was not introduced until 2009. This is illustrated by the fact that in one case PCR analysis allowed for diagnosis four months postmortem.

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9. The value of an artificial neural network in the decision-making for prostate biopsies RP Meijer1, EFA Gemen2, IEW van Onna4, JC vd Linden3, HP Beerlage1, GCM Kusters2 Department of Urology, 2Laboratory of Clinical Chemistry and Haematology, 3Laboratory of Pathology, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch, The Netherlands, 4Department of Urology, Amphia Ziekenhuis, Breda Purpose In the majority of patients that are subjected to prostate biopsies, no prostate carcinoma (PCA) is found. It is important to prevent unnecessary biopsies since serious complications may occur. An artificial neural network (ANN) may be able to predict the risk of the presence of prostate cancer (PCa). Methods Included were all patients, who underwent transrectal ultrasound-guided prostate biopsies between June 2006 and June 2007 with a total PSA (tPSA) level between 2−20 μg/L. The patients were divided in two groups according to their tPSA level (2−10 μg/L and 10−20 μg/L). The ANN ProstataClass of the Universitätsklinikum Charité in Berlin version 9/29/2003 and the new ANN ProstataClass HCS 2008/4.2 was used. The predictions of the ANN were compared to the pathology results of the biopsies. Results Overall 165 patients were included. PCa was diagnosed in 53 patients, whereas the ANN predicted ‘no risk’ in 19 of these patients (36%). The new version of the ANN uses a lower cut off value, thereby predicting minimal risk in 7 of these patients (13%). Conclusions The ANN resulted in a false negative rate of 36%, missing PCa in 19 patients. As expected, by lowering the cut off, the application of the new ANN results in a false negative rate of 7% and will advice to take more biopsies in 52 patients with no proven PCa. We conclude that both the ANN and the new ANN are insufficient to predict the risk of presence of PCa reliably, for use in an outpatient-clinical setting.

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BIJLAGE I Wetenschappelijke publicaties 2009-2010 opgenomen in PubMed Volgorde op PubMed ID nummer. Waar mogelijk is een samenvatting van de publicatie opgenomen. De artikelen worden in het overzicht opgenomen op basis van het jaar van publicatie (dus niet het jaar van Epub).

PMID: 18249050 De Wijn RS, van der Heijden EP, Kon M. On lipoma of the buccal fat pad: report of two cases and review of the literature. J Plast Reconstr Aesthet Surg. 2009 Jan;62(1):28-35. The buccal fat pad (BFP) has been the subject of numerous publications regarding its anatomy and clinical implications, however our interest in the pathology was aroused by two cases of lipoma originating from the BFP that were particularly interesting as one lipoma was congenital and the other recurred. A search of the international literature revealed a further 27 cases of BFP lipoma dating from 1848 to 2002. This suggests it is a rare entity but the authors suspect it to be under reported because of unfamiliarity with the possibility and the various atypical characteristics that were observed. Firstly, BFP lipomas appear to be congenital relatively often. Also, many are histological variants such as the spindle-cell lipoma, which could be associated with a more diffuse growth in the various extensions. As the deep extensions are not routinely removed due to the difficulty of the procedure, this could result in incomplete resection and recurrence. A possible explanation is the hypothesis that the BFP has a different embryological origin than subcutaneous fat. More importantly, well-differentiated liposarcoma of the BFP has also been described, which may be clinically and histologically indistinguishable from spindlecell lipoma. Therefore, the authors recommend a careful workup of every mass of the buccal space with consideration of the BFP as a possible origin. Detailed knowledge of the anatomy and extensive MR-imaging are paramount in guiding the surgical approach by visualising the extent of growth in the various extensions, and determining if the radiological picture is suggestive of liposarcoma.

PMID: 18270659 Van Geest-Daalderop JH, Hutten BA, Péquériaux NC, Levi M, Sturk A. Improvement in the regulation of the vitamin K antagonist acenocoumarol after a standard initial dose regimen: prospective validation of a prescription model. J Thromb Thrombolysis. 2009 Feb;27(2):207-14. BACKGROUND: In a retrospective study we have developed a model which determines the dose of acenocoumarol based on the age of the patient and on the first INR obtained after a standard initial loading dose. The group of patients of this study

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was used as the control group of the present study. AIM: The aim of this study was to prospectively validate the model and to assess whether the use of this model improves the quality of the treatment in the 0-2 months study period. PATIENTS AND METHODS: In 197 patients the model was evaluated by (1) in the initial phase: comparison of INRs with the control group, after assessing the dose according to the model, and (2) in the 0-2 months period: calculation of the percentage of time spent in the therapeutic target range compared to the control group. Furthermore, the eventual dose was compared to the dose of the model when the INRs were within the therapeutic target range for the first time and on two successive occasions. RESULTS: (1) When dosed according to the model, 50% of INRs in the total group were within the therapeutic target range compared to 45% in the control group, and (2) the percentage time spent within this range was 68 in the total group compared to 63 in the control group (P = 0.0013). When the INRs were within the range for the first time and successively twice, the eventual doses were similar to the model in 59 and 50%, respectively. About 20% of the patients did not achieve two successive INRs within the range. CONCLUSIONS: Using the model the quality of treatment improved. We advice to use a standardized individualized dose regimen at the initiation of vitamin K antagonist treatment.

PMID: 18541262 Brokelman WJ, Holmdahl L, Janssen IM, Falk P, Bergström M, Klinkenbijl JH, Reijnen MM. Decreased peritoneal tissue plasminogen activator during prolonged laparoscopic surgery. J Surg Res. 2009 Jan;151(1):89-93. BACKGROUND: Peritoneal fibrinolysis is crucial in the peritoneal healing processes and subsequent adhesion formation. During conventional surgery, the peritoneal fibrinolytic system is rapidly disturbed. Short-term laparoscopy does not seem to affect peritoneal fibrinolysis. The aim of the present study was to assess the effect of prolonged laparoscopic surgery on peritoneal fibrinolysis. METHODS: Twelve consecutive patients undergoing laparoscopic gastric bypass surgery for morbid obesity were included in the study. During the procedure, biopsies of the parietal peritoneum were taken at the start of the procedure and each 45 min afterward. Tissue samples were homogenized and tissue-type plasminogen activator (tPA) antigen, tPA activity, urokinase-type PA antigen, and plasminogen activating inhibitors type 1 antigen were measured using commercial assay techniques. RESULTS: Both tPA antigen and its activity progressively decreased during the procedure, reaching significant levels after 90 min of surgery. The levels of uPA antigen and plasminogen activating inhibitors antigen did not significantly change throughout the procedure. CONCLUSIONS: As for conventional surgery, prolonged laparoscopic surgery causes a decreased fibrinolytic activity in the peritoneum due to decreased tPA levels.

PMID: 18712278 Verra WC, Snijders TJ, Seute T, Han KS, Nieuwenhuis HK, Rutten GJ. Myeloid Sarcoma presenting as a recurrent, multifocal nerve root entrapment syndrome. J Neurooncol. 2009 Jan;91(1):59-62. BACKGROUND: Myeloid sarcoma is an extramedullary manifestation of haematologic malignancy, most commonly acute myeloid leukemia (AML), which can cause neurological symptoms. CASE DESCRIPTION: A 45-year-old male with a history of AML presented with a lumbosacral nerve root entrapment syndrome followed by cauda equina compression, but without systemic signs of AML recurrence. MRI showed a mass compressing the spinal cord at level L5-S2. After surgically removing the tumour pathologic examination yielded a myeloid sarcoma. Combined chemotherapy and radiation therapy followed. Five months later the patient developed a thoracal (Th10-Th11)

bijlage wetenschappelijke publicaties 2009-2010 opgenomen in pubmed

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radiculopathy due to a relapse of the myeloid sarcoma, followed by C8-Th1-radiculopathy caused by leptomeningeal spread. CONCLUSION: This case forms the first description of recurrent, multifocal and progressive radiculopathy due to myeloid sarcoma. This diagnosis should be considered in patients with radiculopathy with previous haematological malignancy and/ or signs or symptoms of such disease; the absence of systemic disease activity does not rule out myeloid sarcoma.

PMID: 18722048 Van Onna IE, Oddens JR, Kok ET, van Moorselaar RJ, Bosch JL, Battermann JJ. External beam radiation therapy followed by interstitial radiotherapy with iridium-192 for solitary bladder tumours: results of 111 treated patients. Eur Urol. 2009 Jul;56(1):113-21. BACKGROUND: Evaluation of bladder-preserving treatment protocol. OBJECTIVE: To evaluate the long-term results of iridium-192 brachytherapy-based bladder-sparing treatment strategy in patients with solitary invasive bladder tumours. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis of 111 patients with solitary T1G3-T2Gall bladder tumours (< or = 5 cm), who were treated with iridium-afterloading brachytherapy between February 1988 and May 2007. INTERVENTION: After transurethral tumour resection, external beam radiotherapy (28 Gy; 12 fractions) was given, followed by brachytherapy (Iridium-192; 40 Gy). Partial cystectomy was part of the treatment strategy in nine patients. In five of those patients a T3 tumour was found, and they were included in the analysis. MEASUREMENTS: The 5-, 10- and 15-yr overall survival rate (OS); disease-specific survival rate (DSS); and disease-free survival rate (DFS) estimates were determined using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Mean follow-up period was 6.2 yr (range: 0.2-16.3 yr). At the last follow-up 75 patients were alive without evidence of disease, whereas 17 patients had died without evidence of disease. Nineteen patients died of bladder cancer after a mean follow-up period of 2.9 yr (range: 0.5-9.0). OS rates at 5 yr, 10 yr, and 15 yr were 70%, 55%, and 51%, respectively. DSS rates at 5 yr, 10 yr, and 15 yr were 82%, 73% and 73%, respectively. DFS rates at 5 yr, 10 yr, and 15 yr were 60%, 47%, and 23%, respectively. Higher tumour stage (T3 vs T1) was negatively associated with DSS (hazard ratio [HR]:19.8; p=0.01) and DFS (HR: 4.67; p=0.02). No prognostic factor was found for OS. Local recurrence occurred in 27% of patients and salvage cystectomy was performed in 9% of patients. Bladder function was able to be preserved in 99 of 111 patients (89%). CONCLUSIONS: In patients with solitary stage T1-T2 bladder cancer (< or = 5 cm) who refuse radical cystectomy or who are poor candidates for major surgical procedures, this modality is a valuable treatment alternative.

PMID: 18722078 Lips DJ, Barker N, Clevers H, Hennipman A. The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol. 2009 Jan;35(1):3-10. BACKGROUND: Aggressive fibromatosis (syn. desmoid tumor) is a sporadically occurring neoplastic proliferation of fibroblasts originating from musculoaponeurotic planes, forming invasively growing masses without the capability to metastasize. The choice of treatment remains surgical resection with or without radiotherapy, and is characterized by high recurrence rates. Better understanding of the aetiology of aggressive fibromatosis is needed to be able to develop new treatment strategies to cope with the high recurrence rates. METHODS: Relevant studies were identified through a search of the electronic databases PubMed/ Medline. The following search terms were used: ‘aggressive fibromatosis’, ‘desmoid tumor’, ‘adenomatous polyposis coli’, ‘APC’, ‘beta-catenin’, ‘Wnt’, ‘Wingless’ and ‘Wnt/Wingless’. Studies were selected for review on the basis of abstract reading. A hand search was perfor-

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med by checking reference lists in selected articles. RESULTS: The neoplastic nature of aggressive fibromatosis and the role of the adenomatous polyposis coli (APC) and betacatenin signaling cascade in driving the onset and progression of this disease are discussed. CONCLUSION: Mutations in either the APC or beta-catenin genes are likely to be a major driving force in the formation of these desmoid tumors. More research is needed to develop new treatment strategies.

PMID: 18762763 Van der Velden WJ, Herbers AH, Blijlevens NM. Palifermin in allogeneic HSCT: many questions remain. Bone Marrow Transplant. 2009 Jan;43(1):85-6. PMID: 18775627 Van Schaik PM, Hermans E, van der Linden JC, Pruijt JR, Ernst MF, Bosscha K. Micro-metastases in stages I and II colon cancer are a predictor of the development of distant metastases and worse disease-free survival. Eur J Surg Oncol. 2009 May;35(5):492-6. Approximately 30% of the patients with Dukes A/B colon carcinoma will develop loco-regional recurrence or distant metastases. The aim of this study was to evaluate if patients with micro-metastases are at higher risk for developing distant metastases and therefore a worse disease-free survival and overall survival. In the period January 2000-January 2002, 137 patients underwent curative surgery for colon cancer. When patients had a Dukes A/B colon carcinoma, additional staining and sectioning on the harvested lymph nodes were performed retrospectively. Lymph nodes were examined using 4 multilevel sections at 250-mum intervals and stained with Pan-Cytokeratin. There were 11 patients with a Dukes A and 61 patients with a Dukes B colon carcinoma. Twenty-two patients developed metastases in time (group I) whereas 50 patients did not (group II). After additional staining and sectioning 41% of the patients of group I and 16% of the patients of group II showed micro-metastases (p<0.05). The 5-year overall survival rate in the group with micro-metastases was 62% against 79% in the group without micro-metastases. The disease-free survival (DFS) was 51% and 72% (p<0.05), respectively. Patients with micro-metastases develop significant more distant metastases in time and have a significant worse DFS.

PMID: 18805601 Pompen M, Gok M, Novák A, van Wuijtswinkel R, Biesma B, Schramel F, Stigt J, Smit H, Postmus P. Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands. Lung Cancer. 2009 Apr;64(1):110-6. INTRODUCTION: Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. METHODS: A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective


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and reports on 2005 costs. RESULTS: Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. CONCLUSION: These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on both national and local levels, this information is relevant for both policy makers and specialists. These data can also be used in future research to evaluate the economic impact of new therapies in NSCLC, especially of those that aim to treat patients in an outpatient setting.

PMID: 18855027 Van de Veerdonk FL, de Jager CP, Schellekens JJ, Huijsmans CJ, Beaumont F, Hermans MH, Wever PC. Legionella pneumophila DNA in serum samples during Legionnaires’ disease in relation to C-reactive protein levels. Eur J Clin Microbiol Infect Dis. 2009 Apr;28(4):371-6. Legionella pneumophila DNA can be detected in serum from patients with Legionnaires’ disease (LD). We explored this observation studying the kinetics of L. pneumophila DNA in serum samples in relation to C-reactive protein (CRP). Eleven hospitalized patients with LD were studied. Diagnosis was made by Legionella urinary antigen test in 8 patients and seroconversion in 3 patients. A macrophage infectivity potentiator (MIP) real-time PCR was performed on 31 serum samples, including 20 follow-up serum samples. Serum samples obtained on the day of admission were MIP PCR-positive in 7 (64%) and MIP PCR-negative in 4 (36%) patients. Three (75%) of the 4 patients with a MIP PCR-negative serum sample on the day of admission became positive during follow-up. Overall, L. pneumophila DNA was detected in serum samples from 10 of the 11 patients (91%). CRP levels in the 7 patients with a positive MIP PCR serum sample on day of admission (499 +/- 144 mg/l; median +/- SD) were significantly higher than those in the 4 patients with a negative MIP PCR serum sample on the day of admission (244 +/- 97 mg/l). No difference in the severity of the disease on the day of admission was found between these patients. The presence of L. pneumophila DNA in serum is a common phenomenon in hospitalized patients with LD, although in some cases it is not yet present on the day of admission. L. pneumophila DNA in serum on the day of admission correlates with high CRP levels, but not with the severity of the disease.

PMID: 18855048 Ploegmakers MJ, Rutten MJ. Fatal pericardial tamponade after superior vena cava stenting. CardioVascular Interventional Radiology 2009 May;32(3):585-9. We discuss a fatal complication of percutaneous superior vena cava (SVC) self-expandable stent placement in a patient with superior vena cava syndrome (SVCS). The SVCS was caused by a malignant mediastinal mass with total occlusion of the SVC. Twenty-four hours after the procedure, the patient died of a hemopericardial tamponade. In the literature, only seven cases have been described with this life-threatening complication. Patients with a necrotic tumor mass are more likely to develop this complication. Knowledge of this complication may increase patient survival.

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PMID: 18949456 Rozendaal FW, Spronk PE, Snellen FF, Schoen A, van Zanten AR, Foudraine NA, Mulder PG, Bakker J; UltiSAFE investigators. Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: a centre randomised, cross-over, open-label study in the Netherlands. Intensive Care Med. 2009 Feb;35(2):291-8. OBJECTIVE: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. DESIGN: Centre randomised, open-label, crossover, ‘real-life’ study. SETTING: 15 Dutch hospitals. PATIENTS: Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV. INTERVENTIONS: Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine. MEASUREMENTS AND MAIN RESULTS: Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable. CONCLUSIONS: In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS.

PMID: 18958474 Rutten MJ, Collins JM, Maresch BJ, Smeets JH, Janssen CM, Kiemeney LA, Jager GJ. Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MR-arthrography. European Radiology, 2009; 19 (3):722-730. To assess the variability in accuracy of contrast media introduction, leakage, required time and patient discomfort in four different centres, each using a different image-guided glenohumeral injection technique. Each centre included 25 consecutive patients. The ultrasound-guided anterior (USa) and posterior approach (USp), fluoroscopic-guided anterior (FLa) and posterior (FLp) approach were used. Number of injection attempts, effect of contrast leakage on diagnostic quality, and total room, radiologist and procedure times were measured. Pain was documented with a visual analogue scale (VAS) pain score. Access to the joint was achieved in all patients. A successful first attempt significantly occurred more often with US (94%) than with fluoroscopic guidance (72%). Leakage of contrast medium did not cause interpretative difficulties. With US guidance mean room, procedure and radiologist times were significantly shorter (p < 0.001). The USa approach was rated with the lowest pre- and post-injection VAS scores. The four image-guided injection techniques are successful in injection of contrast material into the glenohumeral joint. US-guided injections and especially the anterior approach are significantly less time consuming, more successful on the first attempt, cause less patient discomfort and obviate the need for radiation and iodine contrast.


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PMID: 19001280 Lippert E, Girodon F, Hammond E, Jelinek J, Reading NS, Fehse B, Hanlon K, Hermans M, Richard C, Swierczek S, Ugo V, Carillo S, Harrivel V, Marzac C, Pietra D, Sobas M, Mounier M, Migeon M, Ellard S, Kröger N, Herrmann R, Prchal JT, Skoda RC, Hermouet S. Concordance of assays designed for the quantification of JAK2V617F: a multicenter study. Haematologica. 2009 Jan;94(1):38-45. BACKGROUND: Many different techniques have been designed for the quantification of JAK2V617F allelic burden, sometimes producing discrepant results. DESIGN AND METHODS: JAK2V617F quantification techniques were compared among 16 centers using 11 assays based on quantitative polymerase chain reaction (with mutation-specific primers or probes, or fluorescent resonance energy transfer/ melting curve analysis), allele-specific polymerase chain reaction, conventional sequencing or pyrosequencing. RESULTS: A first series of blinded samples (granulocyte DNA, n=29) was analyzed. Seven assays (12 centers) reported values inside the mean +/- 2SD; the mean coefficient of variation was 31%. Sequencing techniques lacked sensitivity, and strong discrepancies were observed with four techniques, which could be attributed to inadequate standards or to different modes of expression of results. Indeed, quantification of JAK2V617F in relation to another control gene produced higher than expected values, suggesting the possibility of more than two JAK2 copies/cell. After calibration of assays with common 1% to 100% JAK2V617F standards (dilutions of UKE-1 cells in normal leukocytes), 14 centers tested ten new samples. JAK2V617F allelic burdens greater or equal than 1% were then reliably quantified by five techniques -- one allele specificpolymerase chain reaction and four TaqMan allele-specific quantitative polymerase chain reaction assays, including one previously giving results outside the mean +/- 2SD -- with a lower mean coefficient of variation (21%). Of these, only the two TaqMan allele-specific quantitative polymerase chain reaction assays with primer-based specificity could detect 0.2% JAK2V617F. CONCLUSIONS: Techniques expressing the allelic burden as JAK2V617F/total JAK2 and using a common set of standards produced similar quantification results but with variable sensitivity. Calibration to a reference standard improved reproducibility.

PMID: 19056388 Boquoi A, Jover R, Chen T, Pennings M, Enders GH. Transgenic expression of VEGF in intestinal epithelium drives mesenchymal cell interactions and epithelial neoplasia. Gastroenterology 2009; 136:596-606. BACKGROUND & AIMS: Vascular endothelial growth factor (VEGF) is expressed robustly in human colon neoplasia and is a major new “rational” target of therapy for cancers of the colon and other organs. Nonetheless, the mechanism(s) of action of VEGF-targeted therapies and the biologic roles of VEGF in tumorigenesis have not been well defined. We used a transgenic approach to directly test the hypothesis that augmented VEGF expression can drive progression of intestinal neoplasia. METHODS: Transgenic mouse lines were generated with moderate (vilVEGF1) and high (vilVEGF2) VEGF expression from the intestinal epithelium. vilVEGF1 mice were bred to Min mice (adenomatous polyposis coli [APC] +/-). Colon epithelial cells from an APC patient were cocultured with endothelial cells and fibroblasts. RESULTS: vilVEGF mice were generally healthy but displayed red small intestines. Vessels were larger and more numerous in the submucosa but not the mucosa. The mucosa showed striking stromal and epithelial hypercellularity, with increased epithelial proliferation. Many crypts formed cysts composed of relatively undifferentiated epithelial cells surrounded by cells with endothelial and myofibroblast markers. Compared with Min controls, vilVEGF1-Min mice developed 6-fold more intestinal adenomas of all sizes, with more advanced histologic features. Polycystic masses were also observed. Coculture of

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human colonocytes with endothelial cells and fibroblasts directly stimulated colonocyte proliferation. CONCLUSIONS: Augmented VEGF expression from intestinal epithelium potently stimulated cross talk with mesenchymal cells and proliferation of normal and neoplastic epithelium. These effects of VEGF, largely occurring prior to the canonical angiogenic switch in tumors, may be in part independent of angiogenesis.

PMID: 19074204 Van Vugt R, Kruse RR, Fritschy WM, Moll FL. Treatment of dilated venous bypass grafts with an expanded polytetrafluoroethylene-covered nitinol endoprosthesis. Vasc Endovascular Surg. 2009 Apr-May;43(2):190-2. An above-knee femoropopliteal bypass graft constructed of great saphenous vein became dilated in 2 patients 12 and 25 years after surgery. Both patients had several concomitant disorders. The dilations were treated by insertion of an expanded polytetrafluoroethylene-covered nitinol endoprosthesis. There were no major procedural complications. One minor endoleak that developed immediately after endograft placement resolved within 6 weeks. The leg swelling subsided, and the endoprostheses have remained patent for 18 and 24 months, respectively. To our knowledge, these were the first cases in which an endoprosthesis was used to treat dilation of a venous bypass graft.

PMID: 19088476 De With MC, de Vries AM, Kroese AB, van der Heijden EP, Bleys RL, Segal SS, Kon M. Vascular anatomy of the hamster retractor muscle with regard to its microvascular transfer. Eur Surg Res. 2009;42(2):97-105. BACKGROUND: The hamster retractor muscle (RET) is used as an in vivo model in studies of skeletal muscle ischemiareperfusion injury. The RET is unique in that the muscle can be isolated while preserving the primary vascular supply so that its contractile function can be measured simultaneously with local microvascular responses to experimental interventions. The goal of this study was to understand the anatomical origin of the vascular supply to the RET and determine whether the RET can be used as a free flap after surgical isolation of the thoracodorsal vessels. METHODS: Microdissection was performed to determine the anatomy of the vasculature that supplies and drains the RET. RESULTS: Distinct numbers and patterns of feed arteries (2-4) and collecting veins (1-3) were identified (n = 26 animals). Dye injection (n = 8) of the thoracodorsal artery demonstrated that the RET remains perfused following its isolation on the thoracodorsal pedicle. Heterotopic allograft transplantation of the RET (n = 2) was performed by anastomosing the thoracodorsal vessels to the femoral vessels using the end-to-side technique. CONCLUSIONS: The anatomical relationships indicate that the RET can be used as a free flap model for evaluating the effect of preservation strategies and transplantation on skeletal muscle microcirculation and contractile function.

PMID: 19098079 Cobben LP, Bakker OJ, Puylaert JB, Kingma LM, Blickman JG. Imaging of patients with clinically suspected appendicitis in the Netherlands: conclusions of a survey. Br J Radiol. 2009 Jun;82(978):482-5. The aim of this study was to summarize the extent of variation in imaging strategies in patients clinically suspected of having appendicitis. By means of a written survey, the policies for the imaging management of patients clinically suspected of ha-


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ving appendicitis in the Netherlands were inventoried. A questionnaire was sent to the departments of surgery and radiology of all 105 Dutch hospitals, including the 8 academic medical centres, in March 2006. Questionnaires were returned from 98 hospitals. It was found that, in the work-up of patients suspected of having appendicitis, ultrasound or CT was performed in a minority of hospitals for 50% or more of these patients. In the majority of hospitals, it was carried out for less than 50% of these patients. There is a widespread variability in pre-operative imaging regardless of hospital type. This survey shows that, despite the ubiquitous presence of ultrasound and CT in Dutch hospitals, the pre-operative imaging work-up in patients clinically suspected of having acute appendicitis does not reflect this, being performed in only a minority of patients suspected of having acute appendicitis. Radiologists and surgeons alike should be aware of the positive impact of adjunctive imaging in this group of patients - most importantly lowering the negative appendicectomy rate and also lowering total hospital costs.

PMID: 19118129 Van Nes IJ, van der Linden S, Hendricks HT, van Kuijk AA, Rulkens M, Verhagen WI, Geurts AC. Is visuospatial hemineglect really a determinant of postural control following stroke? An acute-phase study. Neurorehabil Neural Repair. 2009 Jul-Aug;23(6):609-14. OBJECTIVE: The purpose of this study was to determine the independent contribution of visuospatial hemineglect to impaired postural control in the acute phase (<2 weeks) of stroke compared with other possible clinical and biological determinants. METHODS: This study was conducted in 4 hospitals in the mid-east region of the Netherlands. A total of 78 consecutive patients with a first-ever acute supratentorial stroke was included. Functional balance was measured with the Trunk Impairment Scale, the Trunk Control Test, the Berg Balance Scale, and the Functional Ambulation Categories. Visuospatial hemineglect was assessed by means of an asymmetry index obtained from the Behavioral Inattention Test. The Motricity Index, vibration threshold, sustained attention, and the presence of hemianopia were registered as other possible clinical determinants. Stepwise backward multiple linear regression analysis was performed introducing all selected clinical determinants as well as age and poststroke time as possible biological determinants. RESULTS: Hemineglect was present in 17 patients (21.8%). The groups with and without hemineglect were different for gender and the proportion of right hemisphere strokes, but not for age, type of stroke, or poststroke time. Neglect patients had on average lower scores on all functional balance tests as well as on the clinical assessments. Multivariate linear regression showed that, besides hemineglect, only muscle strength and age independently contributed to impaired balance explaining 65% to 72% of variance of the selected outcomes. CONCLUSION: This study showed that hemineglect independently contributes to impaired postural control in the acute phase of stroke.

PMID: 19147324 Dassen AE, Lips DJ, Hoekstra CJ, Pruijt JF, Bosscha K. FDG-PET has no definite role in preoperative imaging in gastric cancer. Eur J Surg Oncol. 2009 May;35(5):449-55. BACKGROUND: Gastric cancer is fourth on the incidence list of cancers worldwide with a high disease-related mortality rate. Curation can only be achieved by a radical resection including an adequate lymphadenectomy. However, prognosis remains poor and cancer recurrence rates are high, also due to lymph node metastases. To improve outcome, (neo)adjuvant treatment strategies with chemo- and/or radiotherapy regimes are employed. AIMS: Accurate staging of gastric cancer at primary diagnosis is essential for adequate treatment. In this non-systematic review the role 18-F-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in preoperative staging is investigated. Furthermore, the results of neoadjuvant chemotherapy-induced tumour response monitoring by

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FDG-PET are discussed. RESULTS AND CONCLUSION: It is concluded that currently FDG-PET has no role in the primary detection of gastric cancer due to its low sensitivity. FDG-PET shows, however, slightly better results in the evaluation of lymph node metastases in gastric cancer compared to CT and could have therefore a role in the preoperative staging. Improvement in accuracy could be achieved by using PET/CT or other PET tracers than FDG, but these modalities need further investigation. FDG-PET, however, adequately detects therapy responders at an early stage following neoadjuvant chemotherapy.

PMID: 19155626 Van Vugt R, Bosscha K, van Munster IP, de Jager CP, Rutten MJ. Embolization as treatment of choice for bleeding peptic ulcers in high-risk patients. Dig Surg. 2009;26(1):37-42. BACKGROUND/AIM: Peptic ulcers are the most common cause of acute upper gastrointestinal bleedings in the digestive tract. Most patients are poor surgical candidates. The aim was to describe the efficacy of embolization as the treatment of choice for bleeding peptic ulcers in high-risk patients when endoscopic treatment failed. METHODS: All patients who underwent a selective embolization of branches of the superior mesenteric artery and/or branches of the gastroduodenal artery for a bleeding peptic ulcer in the period January 2004 until December 2007 were included in this retrospective descriptive study. We examined the known risk factors for surgery and mortality in upper gastrointestinal bleeding due to peptic ulcers and describe the clinical course and outcome. Primary endpoints were the primary technical success and the clinical success rates. The secondary endpoint was the 30-day mortality. RESULTS: 16 patients were included. All patients had at least two risk factors for surgery and mortality. The clinical success rate was 81% (13/16). The first embolization failed in 3 patients, 1 was successful re-embolized and 2 were operated upon without re-embolization. The primary technical success rate, i.e. bleedings controlled by radiologic intervention, was 88% (14/16). 6 patients died due to non-embolization-related problems; 5 of them developed upper gastrointestinal bleeding during a stay in the hospital. CONCLUSION: Embolization was a successful, minimal invasive alternative for surgical intervention in high-risk patients with upper gastrointestinal bleeding after failure of endoscopic treatment.

PMID: 19161644 Karagiannis I, Schimmer B, van Lier A, Timen A, Schneeberger PM, van Rotterdam B, de Bruin A, Wijkmans C, Rietveld A, van Duynhoven Y. Investigation of a Q fever outbreak in a rural area of The Netherlands. Epidemiol Infect 2009 Sep;137(9):1283-94. A Q fever outbreak occurred in the southeast of The Netherlands in spring and summer 2007. Risk factors for the acquisition of a recent Coxiella burnetii infection were studied. In total, 696 inhabitants in the cluster area were invited to complete a questionnaire and provide a blood sample for serological testing of IgG and IgM phases I and II antibodies against C. burnetii, in order to recruit seronegative controls for a case-control study. Questionnaires were also sent to 35 previously identified clinical cases. Limited environmental sampling focused on two goat farms in the area. Living in the east of the cluster area, in which a positive goat farm, cattle and small ruminants were situated, smoking and contact with agricultural products were associated with a recent infection. Information leaflets were distributed on a large scale to ruminant farms, including hygiene measures to reduce the risk of spread between animals and to humans.


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PMID: 19169032 Koebrugge B, Koek HL, van Wensen RJ, Dautzenberg PL, Bosscha K. Delirium after abdominal surgery at a surgical ward with a high standard of delirium care: incidence, risk factors and outcomes. Dig Surg. 2009;26(1):63-8. BACKGROUND: Although delirium is a common problem in elderly patients undergoing surgery, standard delirium care is not available in all wards. The object of this study was to determine the incidence, risk factors and outcomes of postoperative delirium among patients aged 65 and above undergoing elective abdominal surgery at a surgical ward with a high standard delirium care. METHODS: Prospective descriptive survey in 71 patients. The Delirium Observation Scale was used to screen for delirium. Patients were classified as having a delirium if they met the DSM IV-criteria. Delirious and nondelirious patients were compared and associated risk factors were calculated using logistic regression analyses. RESULTS: Incidence of postoperative delirium was 24%. Univariate analysis showed that age above 74 years, CST score, ASA score, length of ICU stay, length of hospital stay and number of complications were significant risk factors for delirium. Older age, however, was the only significant risk factor in multivariate analysis (OR 1.16; 95% CI 1.00-1.35; p = 0.05). Lastly, mortality was significantly higher in the delirium group (29.4 vs. 3.7%; p = 0.001). CONCLUSION: At a surgical ward with high standard delirium care, the incidence of delirium was 24% and mortality was higher in delirious patients undergoing elective abdominal surgery.

PMID: 19185657 Brink M, Kool DR, Dekker HM, Deunk J, Jager GJ, van Kuijk C, Edwards MJ, Blickman JG. Predictors of abnormal chest CT after blunt trauma: a critical appraisal of the literature. Clin Radiol. 2009 Mar;64(3):272-83. AIM: To identify and to evaluate predictors that determine whether chest computed tomography (CT) is likely to reveal relevant injuries in adult blunt trauma patients. METHODS: After a comprehensive literature search for original studies on blunt chest injury diagnosis, two independent observers included studies on the accuracy of parameters derived from history, physical examination, or diagnostic imaging that might predict injuries at (multidetector row) CT in adults and that allowed construction of 2x2 contingency tables. For each article, methodological quality was scored and relevant predictors for injuries at CT were extracted. For each predictor, sensitivity, specificity, positive and negative likelihood ratio and diagnostic odds ratio (DOR) including 95% confidence intervals were calculated. RESULTS: Of 147 articles initially identified, the observers included 10 original studies in consensus. Abnormalities at physical examination (abnormal respiratory effort, need for assisted ventilation, reduced airentry, coma, chest wall tenderness) and pelvic fractures were significant predictors (DOR: 2.1-6.7). The presence of any injuries at conventional radiography of the chest (eight articles) was a more powerful significant predictor (DOR: 2.2-37). Abnormal chest ultrasonography (four articles) was the most accurate predictor for chest injury at CT (DOR: 491-infinite). CONCLUSION: The current literature indicates that in blunt trauma patients with abnormal physical examination, abnormal conventional radiography, or abnormal ultrasonography of the chest, CT was likely to reveal relevant chest injuries. However, there was no strong evidence to suggest that CT could be omitted in patients without these criteria, or whether these findings are beneficial for patients.

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PMID:19191069 Frankhuisen R, Van Herwaarden MA, Scheffer RC, Hebbard GS, Gooszen HG, Samsom M. Increased intragastric pressure gradients are involved in the occurrence of acid reflux in gastroesophageal reflux disease. Scand J Gastroenterol. 2009;44(5):545-50. OBJECTIVE: Increased pressure gradients across the esophagogastric junction (DeltaEGJp) play a role in gastroesophageal flow during TLESR. The aim of this study was to further explore DeltaEGJp in patients with gastroesophageal reflux disease (GERD) and controls. MATERIAL AND METHODS: Twenty GERD patients were studied along with 20 control subjects. High resolution manometry and pH recording were performed 1 h before and 2 h after a liquid meal (500 ml/300 kcal). DeltaEGJp was calculated at the start of a TLESR and at 180, 60, and 10 s before TLESR. RESULTS: DeltaEGJp at the start of a TLESR and at 180, 60, and 10 s before TLESR was markedly increased in GERD patients compared with that in control subjects (9.9 mmHg and 7.5 mmHg, respectively; p<0.05). Whilst intragastric pressure gradients in GERD patients were increased compared with those in controls (4.6 mmHg and 2.5 mmHg, respectively; p<0.01), intraesophageal pressure gradients were similar in both groups. Furthermore, in controls, first- and second-hour postprandial intragastric pressures were decreased compared with in fasting periods (1.9 +/- 0.4 mmHg and 2.1 +/- 0.4 mmHg versus 3.5 +/- 0.4 mmHg; p<0.05), while this was not observed in GERD patients. CONCLUSIONS: In GERD patients, DeltaEGJp is greater than that in controls both before and during TLESR. This phenomenon is caused by increased intragastric pressure and might contribute to increased rates of acid reflux during TLESR in GERD patients.

PMID: 19208346 Kuiper EM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen ThJ, Haagsma EB, Houben MH, Witteman BJ, van Erpecum KJ, van Buuren HR; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009 Apr;136(4):1281-7. BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) improves laboratory liver test results in patients with primary biliary cirrhosis (PBC). Few studies have assessed the prognostic significance of biochemical data collected following UDCA treatment. We performed a prospective multicenter study of patients with PBC treated with UDCA to compare prognosis with biochemical response. METHODS: PBC was classified as early (pretreatment bilirubin and albumin levels normal), moderately advanced (one level abnormal), or advanced (both levels abnormal). Biochemical response was defined as proposed by Pares (decrease in alkaline phosphatase [ALP] level>40% of baseline level or normal level), Corpechot (ALP level<3-fold the upper limit of normal [ULN], aspartate aminotransferase level<2-fold the ULN, bilirubin level<1-fold the ULN), and our group (Rotterdam; normalization of abnormal bilirubin and/or albumin levels). RESULTS: The study included 375 patients, and median follow-up time was 9.7 (range, 1.0-17.3) years. The prognosis for early PBC was comparable with that of the Dutch population and better than predicted by the Mayo risk score. Survival of responders was better than that of nonresponders, according to Corpechot and Rotterdam criteria (P<.001). Prognosis of early PBC was comparable for responders and nonresponders; prognosis of responders was significantly better in those with (moderately) advanced disease. CONCLUSIONS: Prognosis for UDCA-treated patients with early PBC is comparable to that of the general population. Survival


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of those with advanced PBC with biochemical response to UDCA is significantly better than for nonresponders. Thus, UDCA may be of benefit irrespective of the stage of disease. Prognostic information, based on bilirubin and albumin levels, is superior to that provided by ALP levels.

PMID: 19210503 Kroft EB, Creemers MC, van den Hoogen FH Boezeman JB, de Jong EM. Effectiveness, side-effects and period of remission after treatment with methotrexate in localized scleroderma and related sclerotic skin diseases: an inception cohort study. Br J Dermatol. 2009;160:1075-82. BACKGROUND: Detailed information is lacking on effectiveness of methotrexate (MTX) in sclerotic skin diseases, side-effects, and duration of remission after discontinuation. OBJECTIVES: To determine effectiveness, side-effects and period of remission gained by use of MTX in sclerotic skin diseases. METHODS: All patients with a sclerotic skin disease who were treated with MTX (group A) or MTX with corticosteroids (CS) (group B) between 1995 and 2007 were evaluated. Detailed information was collected on dosage and duration of MTX treatment, concomitant immunosuppressive medication and CS treatment, effectiveness, side-effects, duration of the remission period, and time until restart. RESULTS: Fifty-eight patients (A, n = 47; B, n = 11) were evaluated. Clinical assessment revealed that 38 patients (81%) treated with MTX and 11 patients (100%) treated with MTX + CS showed improvement of sclerotic skin. After one treatment course 51% of the patients treated with MTX and 73% treated with MTX + CS reached remission status with a median followup time of 55 and 58 months. Patients showing relapse still responded to a second and even to a third course of MTX. Patients who showed a relapse had received a lower cumulative dose, due to a shorter period of treatment with MTX in the first course. Serious side-effects were seen in six patients (10%). CONCLUSIONS: MTX was an effective treatment for various sclerotic skin diseases with a long period of remission and relatively low toxicity. Patients showing relapse still responded to a second and third course of MTX.

PMID: 19210517 Poodt AE, Driessen GJ, de Klein A, van Dongen JJ, van der Burg M, de Vries E. TACI mutations and disease susceptibility in patients with common variable immunodeficiency. Clin Exp Immunol. 2009 Apr;156(1):35-9. The most prevalent primary immunodeficiency is common variable immunodeficiency (CVID). Mutations have been described in four genes, ICOS, CD19, BAFF-R and TNFRSF13B (encoding TACI), together associated with 10-15% of CVID cases. We investigated a family with CVID and identified the heterozygous C104R TNFRSF13B mutation in two of the three index-children with CVID, a mother with selective immunoglobulin A deficiency, a mother with recurrent infections and a healthy grandfather. Remarkably, we did not find the TNFRSF13B mutation in the third index-child with CVID, despite his hypogammaglobulinaemia and decreased response to unconjugated pneumococcal vaccine. This family illustrates that TNFRSF13B mutations induce disease susceptibility rather than cause disease directly. Apparently, other genetic or environmental factors, still to be identified, contributed to the development of CVID in this family. Consequently, TNFRSF13B mutations must be interpreted with caution in the clinical setting.

PMID: 19229448 Meijer JW, Voerman GE, Santegoets KM, Geurts AC. Short-term effects and long-term use of a hybrid orthosis for neuromuscular electrical stimulation of the upper

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extremity in patients after chronic stroke. J Rehabil Med. 2009 Feb;41(3):157-61. OBJECTIVE: To associate the short-term effects of the Handmaster orthosis on disabling symptoms of the affected upper extremity with long-term Handmaster orthosis use after stroke. DESIGN: Historic cohort study. PATIENTS: Patients with chronic stroke. METHODS: The Modified Ashworth Scale (0-5) for wrist (primary outcome) and elbow flexor hypertonia, visual analogue scale (0-10) for pain, oedema score (0-3), and passive range of wrist flexion and extension (pROM, degrees) were assessed prior to Handmaster orthosis prescription (T0), after 6 weeks try-out (T1) and a subsequent 4 weeks withhold period (T2). Long-term use was evaluated using a questionnaire. Non-parametric analyses and predictive values were used for statistical analyses. RESULTS: Of the 110 included patients 78.2% were long-term Handmaster orthosis users. Long-term users showed significant short-term (T0-T1) improvements on all impairment scores and a significant relapse of wrist and elbow Modified Ashworth Scale (T1-T2). Non-users showed significant short-term effects on elbow Modified Ashworth Scale and visual analogue scale only. Positive predictive values of short-term effects for long-term use varied between 75% and 100%, with 85% (95% confidence interval (CI) 0.72-0.93) for wrist Modified Ashworth Scale. Negative predictive values were low (11-27%). CONCLUSION: Short-term Handmaster orthosis effects were generally beneficial for hypertonia, pain, oedema, and pROM, especially in long-term users. Short-term beneficial effects were highly predictive for long-term use, but not for non-use.

PMID: 19235339 Persoon MC, Scherpbier AJ, Oei SG, Meijerink WJ, Schijven MP, Schout B, Beerlage HP, Hendrikx AJ. Learning laparoscopy without patients Ned Tijdschr Geneeskd. 2009 Jan 17;153(3):60-2. PMID: 19235344 Consten D, de Bruin JP, Bots RS, Hamilton CJ, Peeters MF. In vitro maturation of human egg cells. Introduction of a new artificial reproduction technique in the Netherlands. Ned Tijdschr Geneeskd. 2009 Jan 17;153(3):82-6. PMID: 19235346 Lips DJ, Koning OH. Coral reef syndrome: a thoracic aorta stenosis as explanation for a collection of symptoms. Ned Tijdschr Geneeskd. 2009 Jan 17;153(3):91-4. PMID: 19249038 Berger LP, Scheffer RC, Weusten BL, Seldenrijk CA, de Bruin PC, Timmer R, Stolk MF. The additional value of EUS-guided Tru-cut biopsy to EUS-guided FNA in patients with mediastinal lesions. Gastrointest Endosc. 2009 May;69(6):1045-51. BACKGROUND AND OBJECTIVE: EUS-guided FNA is a sensitive method to obtain cytologic specimens from solid lesions in close proximity to the GI tract. Although FNA provides cells for analysis, large-caliber Tru-cut biopsy (EUS-TCB) needles obtain samples that can be used for additional histopathologic analysis. We assessed the additional diagnostic yield of EUS-TCB in patients with solid mediastinal lesions in whom EUS-FNA was performed. PATIENTS AND DESIGN: In the period from July 2003 to July 2007, all patients with mediastinal lesions accessible to EUS-FNA


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and EUS-TCB were evaluated. In all patients, a mean of 3 passes of EUS-FNA was followed by EUS-TCB. Cytologic and histologic specimens were evaluated by 2 pathologists blinded for patient condition. A final diagnosis was obtained by combining all information present (EUS-FNA and EUS-TCB results, mediastinoscopy, bronchoscopy [if performed], and other investigations). RESULTS: The diagnostic accuracy of EUS-FNA, EUS-TCB, and the combination of both techniques was 93%, 90%, and 98%, respectively (not significant). In EUS-FNA-negative patients, EUS-TCB provided a final diagnosis in an additional 3 patients (5%). Malignant disease found by EUS-FNA could be specified by EUS-TCB in 15 patients (25% of patients). The granulomatous disease established by cytologic samples of clinically suspected tuberculosis could be specified by EUS-TCB in 2 patients (3%). In 1 patient (2%), both FNA and TCB were inconclusive. LIMITATIONS: Retrospective study. CONCLUSIONS: The diagnostic yield of EUS-FNA and EUS-TCB is comparable. We recommend limiting the use of EUS-TCB to specific cases in which EUS-FNA is not conclusive.

PMID: 19250275 Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009 May;156(2):189-93. Down syndrome (DS) is the most frequent cause of mental retardation in man. Immunological changes in DS have been observed since the 1970s. The neurological system appears to be ageing precociously, with early occurrence of Alzheimer disease; until now, the observed immunological differences have been interpreted in the same context. Looking back at past and present results of immunological studies in DS children in relation to the clinical consequences they suffer, we conclude that it is more likely that the DS immune system is intrinsically deficient from the very beginning.

PMID: 19251852 Budding AE, Ingham CJ, Bitter W, Vandenbroucke-Grauls CM, Schneeberger PM. The Dienes phenomenon: competition and territoriality in Swarming Proteus mirabilis. J Bacteriol. 2009 Jun;191(12):3892-900. When two different strains of swarming Proteus mirabilis encounter one another on an agar plate, swarming ceases and a visible line of demarcation forms. This boundary region is known as the Dienes line and is associated with the formation of rounded cells. While the Dienes line appears to be the product of distinction between self and nonself, many aspects of its formation and function are unclear. In this work, we studied Dienes line formation using clinical isolates labeled with fluorescent proteins. We show that round cells in the Dienes line originate exclusively from one of the swarms involved and that these round cells have decreased viability. In this sense one of the swarms involved is dominant over the other. Close cell proximity is required for Dienes line formation, and when strains initiate swarming in close proximity, the dominant Dienes type has a significant competitive advantage. When one strain is killed by UV irradiation, a Dienes line does not form. Killing of the dominant strain limits the induction of round cells. We suggest that both strains are actively involved in boundary formation and that round cell formation is the result of a short-range killing mechanism that mediates a competitive advantage, an advantage highly specific to the swarming state. Dienes line formation has implications for the physiology of swarming and social recognition in bacteria.

PMID: 19252954 Van la Parra RF, Ernst MF, Bevilacqua JL, Mol SJ, Van Zee KJ, Broekman JM, Bosscha K. Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients

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with a positive sentinel node biopsy: validation of the MSKCC breast nomogram. Ann Surg Oncol. 2009 May;16(5):1128-35. BACKGROUND: Completion axillary lymph node dissection (ALND) remains the standard of care for patients with diseasepositive sentinel lymph nodes (SLN). However, approximately two-thirds will have no additional disease-positive nodes. To identify the patient’s individual risk for non-SLN metastases, the Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram. METHODS: The records of 182 breast cancer patients who underwent SLN and ALND were selected. Serial hematoxylin and eosin (HE) analysis and immunohistochemistry were routinely performed on each sentinel node. For application of the nomogram, the detection method was assigned in two ways: for all metastases visible by serial HE, the method of detection was scored as “serial HE” (method 1), independent of the tumor size, and by a combination of size and staining method (method 2); so macrometastasis were scored as detected by routine HE, micrometastasis by serial HE, and isolated tumor cells by immunohistochemistry. A receiver operating characteristic curve (ROC) was drawn, and the area under the curve was calculated to assess the discriminative power of the nomogram. RESULTS: The area under the ROC was .71 (range, .64-.79) according to method 1 and .75 (range, .67-.88) according to method 2. CONCLUSIONS: Because the variable “method of detection” in the MSKCC nomogram is a surrogate for SLN metastasis size, the size category of the SLN metastasis can be used in applying the nomogram to patients in whom the SLN histologic analysis is performed by a much different procedure than that used to develop the MSKCC nomogram. This results in an improved predictive accuracy.

PMID: 19281697 Bakker OJ, van Santvoort HC, Besselink MG, van der Harst E, Hofker HS, Gooszen HG; Dutch Pancreatitis Study Group. Prevention, detection, and management of infected necrosis in severe acute pancreatitis. Curr Gastroenterol Rep. 2009 Apr;11(2):104-10. The management of infected peripancreatic or pancreatic necrosis in patients with severe pancreatitis has changed considerably in recent years. This review discusses the recent literature on prevention, detection, and management of infected necrosis. Though antibiotics, probiotics, and enteral nutrition have been tried to prevent infected necrosis, only enteral nutrition has consistently proven to be effective. Antibiotics and probiotics have not shown a consistent beneficial effect on outcome. Enteral nutrition reduced infectious complications and mortality in severe pancreatitis, compared with parenteral nutrition. The detection of infection of pancreatic necrosis is important for clinical decision making. Fine-needle aspiration may be used to confirm suspected infection, but if its results will not change clinical decisions, it should be omitted, as it may even introduce infection. Minimally invasive surgical, radiologic, or endoscopic intervention is increasingly being applied. In the absence of level 1 evidence, local expertise dictates which type of intervention is applied.

PMID: 19284647 Van den Broek FJ, de Graaf EJ, Dijkgraaf MG, Reitsma JB, Haringsma J, Timmer R, Weusten BL, Gerhards MF, Consten EC, Schwartz MP, Boom MJ, Derksen EJ, Bijnen AB, Davids PH, Hoff C, van Dullemen HM, Heine GD, van der Linde K, Jansen JM, Mallant-Hent RC, Breumelhof R, Geldof H, Hardwick JC, Doornebosch PG, Depla AC, Ernst MF, van Munster IP, de Hingh IH, Schoon EJ, Bemelman WA, Fockens P, Dekker E. Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study). BMC Surg. 2009 Mar 13;9:4.


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BACKGROUND: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications.The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. METHODS/DESIGN: Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma > or = 3 cm, located between 1-15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment. Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures. Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group. DISCUSSION: The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas.

PMID: 19289623 Goss G, Ferry D, Wierzbicki R, Laurie SA, Thompson J, Biesma B, Hirsch FR, Varella-Garcia M, Duffield E, Ataman OU, Zarenda M, Armour AA. Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status. J Clin Oncol. 2009 May 1;27(13):2253-60. PURPOSE: To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status. PATIENTS AND METHODS: NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored. RESULTS: Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred. CONCLUSION: There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors.

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PMID: 19299851 Schmeits PC, Péquériaux NC, van Geest-Daalderop JH, Ouwehand ME, Coremans AM, Hermans MH, Conemans JM. Investigating unexpected INRs: in search of the culprit--adherence, interactions, genetics, and superwarfarin. Neth J Med. 2009 Feb;67(2):76-8. Treatment with coumarin derivatives is highly individualised due to high intra- and inter-individual variation in dose response and risks of severe bleeding or thromboembolic complications. Treatment focuses on reaching and maintaining a stable target international normalised ratio (INR). However, unexpected INRs that are not explained by noncompliance or vitamin K intake may occur. Here we describe seven cases of unexpected INRs, and provide clues that clarify the underlying mechanism.

PMID: 19307503 Smit EF, Burgers SA, Biesma B, Smit HJ, Eppinga P, Dingemans AM, Joerger M, Schellens JH, Vincent A, van Zandwijk N, Groen HJ. Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer. J Clin Oncol. 2009 Apr 20;27(12):2038-45. PURPOSE: We performed a randomized phase II trial comparing pemetrexed with pemetrexed plus carboplatin (PC) in patients experiencing relapse after platinum-based chemotherapy. PATIENTS AND METHODS: Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer (NSCLC), relapse more than 3 months after platinum-based chemotherapy, normal organ function, and Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned to pemetrexed 500 mg/m(2) (arm A) or carboplatin area under the curve 5 and pemetrexed 500 mg/m(2) (arm B), both administered intravenously every 3 weeks. Response assessment was performed every 6 weeks; toxicity assessment was performed every 3 weeks. Primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), overall survival (OS), and toxicity. The study was designed to detect a 33% decrease in the hazard of disease progression in the combination arm (alpha = 0.05, two-sided log-rank test). Polymorphisms of thymidylate synthase, the reduced folate carrier, gamma-glutamyl hydrolase, and methylenetetrahydrofolate reductase (MTHF) were investigated in peripheral WBCs of consenting patients. RESULTS: Two hundred forty patients were enrolled. Median TTP was 2.8 months for arm A versus 4.2 months for arm B (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = .005). Median OS was 7.6 months and 8.0 months and ORR was 4% and 9% for arms A and B, respectively. Subgroup analyses found adenocarcinoma to be associated with favorable outcome. Toxicities in both arms was negligible, with one potential toxic death in arm A. Patients with MTHFR C677T homozygous mutation had increased progression-free survival compared with patients with wild-type or heterozygous mutations (P = .03). CONCLUSION: PC as second-line treatment for relapsed NSCLC resulted in a significant 33% reduction of the hazard of disease progression as compared with pemetrexed alone.

PMID: 19325905 Hassink RJ, Haerkens-Arends HE, Daniels MC. Extensive right coronary artery thrombosis. Neth Heart J. 2009 Mar;17(3):115-6.


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PMID: 19326699 Dautzenberg PL, Nijboer H, Wouters CJ. A triage system for non-urgent ambulant frail elderly. Tijdschr Gerontol Geriatr. 2009 Feb;40(1):24-8. PURPOSE: This study aimed to examine a triage system for non-urgent ambulant frail elderly. METHODS: Three months prospective evaluation of patients, admitted for an out-hospital evaluation on a geriatric ward of an non-academic teaching hospital and not suitable for a memory clinic or falls clinic. A maximum of four patients entered the triage system at the same moment and a nurse and a physiotherapist investigated these patients separately during 30 minutes in total. After these investigations, triage consensus was reached and immediately thereafter, 2 patients were admitted to a fall clinic, 1 patient was admitted to a consultant and 1 patient was admitted to a resident. For each admission, there were positive and negative reasons defined. RESULTS: During 22 moments of triage, 68 patients were admitted to the different out-hospital evaluations. In 90% positive reasons for triage were used. CONCLUSIONS: A triage system for non-urgent ambulant frail elderly seems to be effective. However, more research is needed.

PMID: 19332456 Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Grönhagen-Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Süleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wüthrich RP, Gottlow M, Johnsson E, Zannad F; AURORA Study Group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009 Apr 2;360(14):1395-407. BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

PMID: 19338383 Van Puijenbroek EP, Conemans JM, Van Grootheest AC.

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Spontaneous ADR Reports as a Trigger for Pharmacogenetic Research: Experiences in the Netherlands. Drug Saf 2009;32(3):255-64. BACKGROUND: Information on genetic polymorphisms in drug-metabolizing enzymes is valuable when analysing the causal relationship between drug intake and an adverse drug reaction (ADR). Patients who have experienced an ADR should be informed about the possible existence of genetic polymorphisms that may contribute to the occurrence of ADRs, since this will allow adequate dosing of future medication.In collaboration with the regional hospital pharmacy Ziekenhuisapotheek NoordOost-Brabant (ZANOB), the Netherlands Pharmacovigilance Centre Lareb developed a method for informing physicians or pharmacists and their patients about a possible pharmacogenetic involvement in the pathogenesis of the reported ADR and for offering easy access to genotyping if requested by the treating physician. An anonymized copy of the test results could be used for the interpretation of possible signals at the pharmacovigilance centre. OBJECTIVES: The aim of this study was to gain insight into the feasibility of informing the reporting physician or pharmacist about possible involvement of a genetic polymorphism and subsequent genotyping of patients based on ADR reports received by the Netherlands Pharmacovigilance Centre. RESULTS: A total of 38 reports were selected in which genotyping was considered useful. In 15 of 38 cases (39.5%), the reporting health professionals actually initiated genotyping. The majority of the drugs implicated in causing ADRs were selective serotonin reuptake inhibitors, followed by other antidepressants and antipsychotic drugs. No logistical problems were encountered during this study. CONCLUSION: The level of participating health professionals in genotyping their patients was relatively high. Apparently, reporting health professionals share the vision that information on pharmacogenetic characteristics of their individual patients is important. The use of an existing infrastructure for DNA sampling that is familiar to the patients and health professionals may have contributed to the high response rate.Pharmacovigilance centres may suggest pharmacogenetic investigation and subsequent individualized pharmacogenetic counselling after a reported ADR. These centres can also be a valuable starting point for pharmacogenetic studies, since data from different sources can be combined in the assessment of the causal relationship between drug intake and an ADR. This study shows that genotyping initiated by pharmacovigilance centres is indeed feasible, when using the standard laboratory testing infrastructure.

PMID: 19341194 Van Vugt R, Bosscha K, Olsman J, Jager GJ, de Jager CP. Management of hepatic trauma: a 9-year experience in ’s-Hertogenbosch. Acta Chir Belg. 2009 Jan-Feb;109(1):42-6. BACKGROUND: In patients who sustain abdominal trauma the liver is the most frequently injured organ. Although treatment for haemodynamically unstable patients remains urgent surgery, there has been a shift of management in haemodynamacally stable patients towards non-operative management. We performed an outcome assessment of traumatic hepatic injury. METHODS: A retrospective study was performed to assess incidence, mechanisms, management and outcome of traumatic liver injury in the region of ’s-Hertogenbosch, The Netherlands, in the period 1999-2007. RESULTS: A total of 47 patients were identified. Thirty-six patients had blunt hepatic trauma, eleven sustained penetrating hepatic injury. In 67% (n = 24) of the blunt hepatic trauma patients the initial intention was to treat non-operatively. Yet, two patients underwent explorative laparotomy after one and two days. In the penetrating liver trauma patients, 91% (n = 10) underwent urgent surgery. In total, 31 of 47 patients were treated conservatively. CONCLUSION: Blunt hepatic trauma is the most common cause of hepatic trauma. Most patients sustaining hepatic trauma can be managed conservatively at a dedicated ICU and/or surgical trauma ward.


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PMID: 19342504 De Waard H, van ’t Sant P. Use of serum myoglobin assays for urine myoglobin measurements can cause false-negative results. Clin. Chem. 2009 Jun;55(6):1240-1. PMID: 19344081 Binkhorst M, de Leeuw N, Otten BJ. A healthy, female chimera with 46,XX/46,XY karyotype. J Pediatr Endocrinol Metab 2009; 22: 97-102. We report a healthy and unambiguously female newborn, whose phenotypic sex contradicted the expected male sex based on previously performed prenatal cytogenetic analysis. Both 46,XX and 46,XY cells were detected in a villus sample, the former having been attributed to maternal cell contamination. Postnatal karyotyping in peripheral lymphocytes confirmed the presence of two cell lines, one 46,XX (70%) and one 46,XY (30%). After exclusion of alternative explanations for the observed genotype, a diagnosis of chimerism was made. Chimeras containing cell lines of opposite sex usually feature ovotesticular development with associated genital ambiguity. To account for the normal female appearance of our patient, we postulate the exclusive involvement of 46,XX cells in gonad formation.

PMID: 19350292 Daha TJ, Bilkert-Mooiman MA, Ballemans C, Frijstein G, Keeman JN, de Man RA, van Steenbergen JE, Weers-Pothoff G, Zaaijer HL. Hepatitis B virus infected health care workers in The Netherlands, 2000-2008. Eur J Clin Microbiol Infect Dis 2009;28:1041-4. In response to the confirmed transmission of hepatitis B virus (HBV) from a surgeon to several patients in the Netherlands, a ‘Committee for Prevention of Iatrogenic Hepatitis B’ was established in 2000. During the years 2000-2008, the committee reviewed 99 cases of HBV-infected health care workers. Fifty of them were found to perform exposure prone procedures (EPPs). Because of high levels of HBV DNA (>100,000 copies/ml), a ban on performing EPPs was applied in 11/50 cases; 25/50 low-viremic health care workers were allowed to continue EPPs while their HBV load was being monitored; and 14/50 cases had stopped working or changed profession. In five restricted workers who started oral antiviral treatment, HBV replication was persistently suppressed, enabling the ban on EPPs to be lifted. Throughout the European Union different levels of HBV viremia have been chosen, above which health care workers are not allowed to perform EPPs. It remains unknown how this affects the safety of patients. Application in the Netherlands of a European or a British guideline would have, respectively, doubled or tripled the number of restricted health care workers.

PMID: 19365285 De Mast Q, Beutler JJ. The prevalence of atherosclerotic renal artery stenosis in risk groups: a systematic literature review. J Hypertens. 2009 Jul;27(7):1333-40. OBJECTIVE: We performed a literature review and analysis to improve the insight in the prevalence of renal artery stenosis (RAS) in risk groups. METHODS: Relevant studies were identified by a MEDLINE and EMBASE database search (1966 to December 2007),

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complemented by hand searching of reference lists. Review was restricted to English language studies, using any form of angiography as diagnostic method. Studies were grouped in risk group categories sharing similar clinical characteristics, and pooled prevalence rates were calculated for each category. RESULTS: Forty studies, involving a total number of 15 879 patients, were identified. The following pooled prevalence rates (95% confidence interval; sample size risk group) of RAS were found: suspected renovascular hypertension, 14.1% (12.715.8%; n = 1931); hypertension and diabetes mellitus, 20% (14.9-25.1%; n = 240); coronary angiography (CAG) in consecutive patients, 10.5% (9.8-11.2%; n = 8011); CAG in hypertensive patients, 17.8% (15.4-20.6%; n = 836); CAG and suspected renovascular disease, 16.6% (14.8-18.5%; n = 1576); congestive heart failure, 54.1% (45.7-62.3%; n = 135); peripheral vascular disease, 25.3% (23.6-27.0%; n = 2632); abdominal aortic aneurysm, 33.1% (27.4-39.2%; n = 239) and end-stage renal failure, 40.8% (27-55.8%; n = 49.) In patients with an incidentally discovered RAS, hypertension and renal failure were present in 65.5 and 27.5%, respectively. CONCLUSION: RAS has a high prevalence in risk groups, especially in those with extrarenal atherosclerosis, end-stage renal failure and heart failure. These findings are important when screening for RAS or prescription of an angiotensin converting enzyme inhibitor or angiotensin-II receptor blocker is considered.

PMID: 19374097 Ritchie ED, Jager GJ, van der Linden JC, Bosscha K. Three adults with intra-abdominal lymphangioma. Ned Tijdschr Geneeskd. 2009 Mar 7;153(10):456-9. PMID: 19383834 Van Dijk S, Scharloo M, Kaptein AA, Thong MS, Boeschoten EW, Grootendorst DC, Krediet RT, Dekker FW; NECOSAD Study Group, Apperloo AJ, Bijlsma JA, Boekhout M, Boer WH, van der Boog PJ, Büller HR, van Buren M, de Charro FT, Doorenbos CJ, van den Dorpel MA, van Es A, Fagel WJ, Feith GW, de Fijter CW, Frenken LA, van Geelen JA, Gerlag PG, Grave W, Gorgels JP, Huisman RM, Jager KJ, Jie K, Koning-Mulder WA, Koolen MI, Hovinga TK, Lavrijssen AT, Luik AJ, van der Meulen J, Parlevliet KJ, Raasveld MH, van der Sande FM, Schonck MJ, Schuurmans MM, Siegert CE, Stegeman CA, Stevens P, Thijssen JG, Valentijn RM, Vastenburg GH, Verburgh CA, Vincent HH, Vos PF. Patients’ representations of their end-stage renal disease: relation with mortality. Nephrol Dial Transplant 2009 Oct;24(10):3183-5. BACKGROUND: Self-regulation theory explains how patients’ illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients’ representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients’ personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.


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PMID: 19384222 Richir MC, van Lambalgen AA, Teerlink T, Wisselink W, Bloemena E, Prins HA, de Vries TP, van Leeuwen PA. Low arginine/asymmetric dimethylarginine ratio deteriorates systemic hemodynamics and organ blood flow in a rat model. Crit Care Med. 2009 Jun;37(6):2010-7. OBJECTIVE: Both arginine and asymmetric dimethylarginine (ADMA) play a crucial role in the arginine-nitric oxide pathway. Low arginine and high ADMA levels can be found in critically ill patients after major surgery. The aim of this study was to evaluate the effects of low arginine plasma concentrations in combination with high ADMA plasma concentrations on hemodynamics and organ blood flow. DESIGN: Randomized, placebo-controlled animal laboratory investigation. SUBJECTS: Male Wistar rats (n = 21), anesthetized. INTERVENTIONS: Rats were randomly assigned to three groups: a control group, an ADMA group, or an arginase (ASE)/ADMA group. In the control group, rats received (at t = 0) an intravenous (IV) infusion of 1.5 mL 0.9% NaCl during a 20-minute period. After 60 minutes (t = 60), rats received an IV bolus of 1.0 mL 0.9% NaCl. In the ADMA group, rats received an IV infusion of 1.5 mL 0.9% NaCl during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). In the ASE/ADMA group, rats received an IV infusion of 1.5 mL ASE (3200 IU) solution during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). MEASUREMENTS AND MAIN RESULTS: Infusion of ADMA (20 mg/kg) and ASE (3200 IU) resulted in increased plasma ADMA levels and decreased arginine levels. During the whole experiment, systemic hemodynamics (heart rate, mean arterial pressure [MAP], and cardiac output) were measured. In addition, organ blood flow was measured at t = 90 and t = 180 minutes, using fluorescent microspheres. Compared with the control group, MAP and systemic vascular resistance were increased after infusion of ADMA. Infusion of ASE in combination with ADMA significantly deteriorated systemic hemodynamics (MAP, cardiac output, stroke volume, and systemic vascular resistance) and organ blood flow through the kidney and spleen. In addition, an initial decrease in arterial flow, followed by a later major increase, and panlobular apoptosis and necrosis of the liver was observed. CONCLUSIONS: The current study shows that low arginine plasma levels in combination with high ADMA plasma levels deteriorates systemic hemodynamics and reduces blood flow through the kidney and spleen and liver. These data suggest that a diminished nitric oxide production may be involved in the onset of organ failure.

PMID: 19388726 Van Puijenbroek E, Conemans JM, Van Grootheest K. Spontaneous reports and pharmacogenetics. The role of the pharmacovigilance centre. Drug Saf 2009;32:357-8. PMID: 19398188 Ruiterkamp J, Ernst MF, van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Voogd AC. Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol. 2009 Nov;35(11):1146-51. OBJECTIVE: Recent studies indicate that removal of the primary tumour may have a beneficial effect on mortality risk of patients with primary distant metastatic breast cancer (stage IV), although most of them did not rule out confounding by the presence of co-morbidity. In this retrospective study the impact of surgical resection of the primary tumour on the survival of patients with primary distant metastatic disease is investigated, taking into account the presence of co-morbidity and other potential confounders.

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METHODS: Between 1993 and 2004, 15 769 patients with breast cancer were diagnosed in the south of the Netherlands. This study included the 728 patients with distant metastatic disease at initial presentation, which was 5% of all patients. Of them, 40% had surgery of the primary tumour. Follow-up was carried out until 1 July 2006. RESULTS: Median survival of the patients who had surgery of their primary tumour was significantly longer than for the patients who did not have surgery (31 vs. 14 months). The 5-year survival rates were 24.5% and 13.1%, respectively (p < 0.0001). In a multivariable Cox regression analysis, adjusting for age, period of diagnosis, T-classification, number of metastatic sites, comorbidity, use of loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an independent prognostic factor for overall survival (HR = 0.62; 95% CI 0.51-0.76). CONCLUSION: Removal of the primary tumour in patients with primary distant metastatic disease was associated with a reduction of the mortality risk of around 40%. The association was independent of age, presence of co-morbidity and other potential confounders, but a randomized controlled trial will be needed to rule out residual confounding.

PMID: 19401573 Heesakkers RA, Jager GJ, Hövels AM, de Hoop B, van den Bosch HC, Raat F, Witjes JA, Mulders PF, van der Kaa CH, Barentsz JO. Prostate cancer: detection of lymph node metastases outside the routine surgical area with ferumoxtran-10enhanced MR imaging. Radiology. 2009 May;251(2):408-14. PURPOSE: To prospectively evaluate the feasibility of magnetic resonance (MR) imaging with ferumoxtran-10 in patients with prostate cancer to depict lymph node metastases outside the routine pelvic lymph node dissection (PLND) area. MATERIALS AND METHODS: The study was approved by the institutional review boards at all four hospitals; patients provided written informed consent. Two hundred ninety-six consecutive men (mean age, 67 years; range, 47-83 years) with prostate cancer and an intermediate-to-high risk for nodal metastases (prostate-specific antigen level >10 ng/mL, Gleason score >6, or stage T3 disease) were enrolled. MR lymphography of the pelvis was performed 24 hours after intravenous drip infusion of ferumoxtran-10. Positive nodes at MR lymphography were indicated to be inside or outside the routine dissection area (RDA). On the basis of MR lymphography computed tomographic (CT)-guided biopsy, routine PLND, or MR imagingguided minimal extended PLND was performed. RESULTS: MR lymphography findings were positive in 58 patients. Of these, 44 had histopathologic confirmation of lymph node metastases. In 18 of 44 patients (41%), MR lymphography findings showed nodes exclusively outside the RDA, which were confirmed with MR lymphography-guided extended PLND (n = 13) and CT-guided biopsy (n = 5). In another 18 patients (41%), positive nodes were located both inside and outside the RDA at MR lymphography. In these 18 patients, routine PLND was used to confirm the nodes inside the RDA (n = 11); CT-guided biopsy was used to confirm nodes outside the RDA (n = 7). In the remaining eight patients, MR lymphography findings showed only nodes inside the RDA, which was confirmed with PLND (n = 5) and CT-guided biopsy (n = 3). In 14 of the 58 patients (24%), there was no histologic confirmation. CONCLUSION: In 41% of patients with prostate cancer, nodal metastases outside the area of routine PLND were detected by using MR imaging with ferumoxtran-10.

PMID: 19414832 Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, Braam B, Huysmans FT, Schultze Kool LJ, Rutten MJ, Doorenbos CJ, Aarts JC, Rabelink TJ, Plouin PF, Raynaud A, van Montfrans GA, Reekers JA, van den Meiracker AH, Pattynama PM, van de Ven PJ, Vroegindeweij D, Kroon AA, de Haan MW, Postma CT, Beutler JJ. Stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Ann Intern Med. 2009 Jun 16;150(12):840-8, W150-1.


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BACKGROUND: Little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) and impaired renal function. OBJECTIVE: To determine the efficacy and safety of stent placement in patients with ARAS and impaired renal function. DESIGN: Randomized clinical trial. Randomization was centralized and computer generated, and allocation was assigned by e-mail. Patients, providers, and persons who assessed outcomes were not blinded to treatment assignment. SETTING: 10 European medical centers. PARTICIPANTS: 140 patients with creatinine clearance less than 80 mL/min per 1.73 m(2) and ARAS of 50% or greater. INTERVENTION: Stent placement and medical treatment (64 patients) or medical treatment only (76 patients). Medical treatment consisted of antihypertensive treatment, a statin, and aspirin. MEASUREMENTS: The primary end point was a 20% or greater decrease in creatinine clearance. Secondary end points included safety and cardiovascular morbidity and mortality. RESULTS: Forty-six of 64 patients assigned to stent placement had the procedure. Ten of the 64 patients (16%) in the stent placement group and 16 patients (22%) in the medication group reached the primary end point (hazard ratio, 0.73 [95% CI, 0.33 to 1.61]). Serious complications occurred in the stent group, including 2 procedure-related deaths (3%), 1 late death secondary to an infected hematoma, and 1 patient who required dialysis secondary to cholesterol embolism. The groups did not differ for other secondary end points. LIMITATION: Many patients were falsely identified as having renal artery stenosis greater than 50% by noninvasive imaging and did not ultimately require stenting. CONCLUSION: Stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications. The study findings favor a conservative approach to patients with ARAS, focused on cardiovascular risk factor management and avoiding stenting.

PMID: 19438643 De Jager CP, de Wit NC, Weers-Pothoff G, van der Poll T, Wever PC. Procalcitonin kinetics in Legionella pneumophila pneumonia. Clin Microbiol Infect. 2009 Nov;15(11):1020-5. Little is known about procalcitonin (PCT) levels in patients with community-acquired pneumonia (CAP) caused by Legionella pneumophila. The aim of the present study was to investigate this infection marker in patients admitted with L. pneumophila pneumonia in relation to conventional inflammatory parameters, severity of pneumonia upon admission and clinical outcome. Eighteen patients admitted with CAP caused by L. pneumophila serogroup 1 were retrospectively examined. PCT measurements were carried out during the first week of admission in addition to measurements of Creactive protein (CRP), white blood cell (WBC) count and registration of severity of pneumonia upon admission (CURB-65 score). The mean PCT level upon admission in patients with L. pneumophila pneumonia was 13.5 ng/mL (range 0.3-55.7 ng/mL). Mean CRP level was 397 mg/L (range 167-595 mg/L) and mean WBC count 11.7 x 10(9)/L (range 4.5-20.4 x 10(9)/L). Initial high PCT levels were indicative of more severe disease as reflected by prolonged intensive care unit (ICU) stay and/or in-hospital death. Patients admitted to the ICU showed significantly higher PCT levels compared with the remaining patients [26.7 ng/mL (range 4.6-55.7 ng/mL) vs. 6.9 ng/mL (range 0.3-29.3 ng/mL); p 0.019]. There was a significant correlation between Acute Physiology and Chronic Health Evaluation-II scores upon ICU admission and initial PCT levels upon hospital admission (r = 0.86; p 0.027). Persistently increased PCT levels during treatment were indicative of unfavourable clinical outcome. Conventional inflammatory parameters (CRP and WBC) and the CURB-65 score lacked this discriminatory capacity in our study population. PCT may therefore be a valuable tool in the initial clinical assessment and follow-up of patients with L. pneumophila pneumonia.

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PMID: 19442401 Schimmer B, Dijkstra F, Vellema P, Schneeberger PM, Hackert V, ter Schegget R, Wijkmans C, van Duynhoven Y, van der Hoek W. Sustained intensive transmission of Q fever in the south of the Netherlands, 2009. Euro Surveill 2009;14:pii=19210. The Netherlands is again facing a sharp increase in Q fever notifications, after the unprecedented outbreaks of 2007 and 2008. The most affected province of Noord Brabant has a high density of large dairy goat farms, and farms with abortion waves have been incriminated. Mandatory vaccination of small ruminants has started and should have an effect in 2010. A large multidisciplinary research portfolio is expected to generate better knowledge about transmission and additional control measures.

PMID: 19443491 Veen EJ, Janssen-Heijnen ML, Ritchie ED, Biesma B, van den Bogart MP, Bolhuis RJ. Pneumonectomy for bronchogenic carcinoma: analysis of factors predicting short- and long-term outcome. Interact Cardiovasc Thorac Surg. 2009 Aug;9(2):260-4. The objective of this study was to analyse predictive factors for postoperative and long-term outcome after pneumonectomy. From 1 January 2000 to 1 January 2005 a total of 91 (31%) pneumonectomies were performed. Multivariable analysis for postoperative morbidity, mortality, and long-term survival was performed. Patients over 70 years had 1.5 times higher risk of dying (HR=1.5, 95% CI=1.1-2.0) within five years compared to younger patients, those with co-morbidity had 1.8 times higher risk compared to no co-morbidity (HR=1.8, 95% CI=1.3-2.7) and those with stage IIIA had 2.3 times higher risk of dying compared to stage I (HR=2.3, 95% CI=1.5-3.6). Overall postoperative mortality within 30 days in patients undergoing pneumonectomy was 10% (n=9). Most patients who died postoperatively were 70 years or older, had cardiovascular comorbidity and underwent right-sided pneumonectomy (n=6). Patients over 70 years had three times higher risk of complications compared to younger patients (OR=3.1, 95% CI=1.1-8.2), and patients undergoing right-sided pneumonectomy had 2.4 times higher risk compared to left-sided pneumonectomy (OR=2.4, 95% CI=0.9-6.4). Pneumonectomy is accompanied by high postoperative mortality and morbidity rates, the highest risk in patients over 70 years and right-sided pneumonectomy, and consequently should lead to meticulous patient selection and perioperative care.

PMID: 19461865 Coester AM, Smit W, Struijk DG, Krediet RT. Peritoneal function in clinical practice: the importance of follow-up and its measurement in patients. Recommendations for patient information and measurement of peritoneal function. NDT Plus. 2009 Apr;2(2):104-110. A review is given on peritoneal function, especially ultrafiltration and ultrafiltration failure followed by recommendations on how to translate pathophysiology into clinical practice. The subsequent consequences for management of peritoneal membrane function and for patient information are also included.

PMID: 19477688 Binkhorst M, de Gier RP. A large extra-abdominal prevesical pseudo-cyst in a newborn with posterior urethral valves. J Pediatr Urol 2010; 6: 91-93.


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A male newborn is described, in whom a large extra-abdominal prevesical pseudo-cyst as well as prune-belly features were present, both of which were supposedly secondary to posterior urethral valves. It is postulated that the subvesical obstruction caused pressure build-up in the urinary tract, followed by fetal bladder rupture. The resultant urinoma migrated extra-abdominally. Distension of the urinary tract, bilateral cryptorchidism and abdominal wall laxity contributed to a prune-belly phenotype.

PMID: 19483176 Hoogeveen EK, Stehouwer CD. Exclusion of a case-control study from meta-analysis. Mayo Clin Proc. 2009; 84: 561. PMID: 19486621 Color II Study Group, Buunen M, Bonjer HJ, Hop WC, Haglind E, Kurlberg G, Rosenberg J, Lacy AM, Cuesta MA, D’Hoore A, Fürst A, Lange JF, Jess P, Bulut O, Poornoroozy P, Jensen KJ, Christensen MM, Lundhus E, Ovesen H, Birch D, Iesalnieks I, Jäger C, Kreis M, van riet Y, van der Harst E, Gerhards MF, Bemelman WA, Hansson BM, Neijenhuis PA, Prins HA, Balague C, Targarona E, Luján Mompeán JA, Franco Osorio JD, Garcia Molina FJ, Skullman S, Läckberg Z, Kressner U, Matthiessen P, Kim SH, Poza AA. COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer. Dan Med Bull. 2009 May;56(2):89-91. INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years postoperatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial.

PMID: 19494591 Coester AM, Smit W, Struijk DG, Krediet RT. Fluid transport with time on peritoneal dialysis: the contribution of free water transport and solute coupled water transport. Contrib Nephrol. 2009;163:22-6. Ultrafiltration in peritoneal dialysis occurs through endothelial water channels (free water transport) and together with solutes across small pores: solute coupled water transport. A review is given of cross-sectional studies and on the results of longitudinal follow-up.

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PMID: 19494595 Krediet RT, Sampimon DE, Vlijm A, Coester AM, Struijk DG, Smit W. Biological markers in the peritoneal dialysate effluent: are they useful. Contrib Nephrol. 2009;163:54-9. A review is given on biomarkers in peritoneal effluent. It comprises methods to distinguish between diffusion and local production. This is followed by examples of various biomarkers. Their potential use is discussed in 4 situations: inherent fast transporters, longitudinal follow-up of patients, biocompatibility testing of new dialysis solutions, and their potential use in the detection of patients who are likely to develop encapsulating peritoneal sclerosis.

PMID: 19494600 Krediet RT, Smit W, Coester AM, Struijk DG. Dry body weight and ultrafiltration targets in peritoneal dialysis. Contrib Nephrol. 2009;163:90-5. A review is given on methods that can be used for the assessment of dry body weight in peritoneal dialysis patients. Besides clinical examination, the use of natriuretic hormone concentrations in plasma, and the value of multifrequency bio-impedance analysis is discussed. Ultrafiltration targets as formulated in various guidelines are reviewed. Finally, it is concluded that the ultrafiltration target is the amount required to keep patients euvolemic with an exposure to glucose that is as low as possible.

PMID: 19515608 Van Asten L, van der Lubben M, van den Wijngaard C, van Pelt W, Verheij R, Jacobi A, Overduin P, Meijer A, Luijt D, Claas E, Hermans MH, Melchers W, Rossen J, Schuurman R, Wolffs P, Boucher C, Schirm J, Kroes L, Leenders AC, Galama J, Peeters M, van Loon A, Stobberingh E, Schutten M, Koopmans M. Strengthening the diagnostic capacity to detect Bio Safety Level 3 organisms in unusual respiratory viral outbreaks. J Clin Virol. 2009 Jul;45(3):185-90. BACKGROUND: Experience with a highly pathogenic avian influenza outbreak in the Netherlands (2003) illustrated that the diagnostic demand for respiratory viruses at different biosafety levels (including BSL3), can increase unexpectedly and dramatically. OBJECTIVES: We describe the measures taken since, aimed at strengthening national laboratory surge capacity and improving preparedness for dealing with diagnostic demand during outbreaks of (emerging) respiratory virus infections, including pandemic influenza virus. STUDY DESIGN: Academic and peripheral medical-microbiological laboratories collaborated to determine minimal laboratory requirements for the identification of viruses in the early stages of a pandemic or a large outbreak of avian influenza virus. Next, an enhanced collaborative national network of outbreak assistance laboratories (OAL) was set up. An inventory was made of the maximum diagnostic throughput that this network can deliver in a period of intensified demand. For an estimate of the potential magnitude of this surge demand, historical counts were calculated from hospital- and physician-based registries of patients presenting with respiratory symptoms. RESULTS: Number of respiratory physician-visits ranged from 140,000 to 615,000 per month and hospitalizations ranged from 3000 to 11,500 per month. The established OAL-network provides rapid diagnostic response with agreed


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quality requirements and a maximum throughput capacity of 1275 samples/day (38,000 per month), assuming other routine diagnostic work needs to be maintained. CONCLUSIONS: Thus surge demand for diagnostics for hospitalized cases (if not distinguishable from other respiratory illness) could be handled by the OAL network. Assessing etiology of community acquired acute respiratory infection however, may rapidly exceed the capacity of the network. Therefore algorithms are needed for triaging for laboratory diagnostics; currently this is not addressed in pandemic preparedness plans.

PMID: 19516032 Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Piérart M, Mauer ME, Collette L; EORTC Radiation Oncology Group and Genito-Urinary Tract Cancer Group. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009 Jun 11;360(24):2516-27. BACKGROUND: The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. METHODS: We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. RESULTS: A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. CONCLUSIONS: The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer.

PMID: 19540155 Meijer A, Beerens A, Claas E, Hermans M, de Jong A, Molenkamp R, Niesters H, Overduin P, Rossen J, Schuurman R, Wolffs P, Fouchier R, Osterhaus A, Schutten M, Koopmans M. Preparing the outbreak assistance laboratory network in the Netherlands for the detection of the influenza virus A(H1N1) variant. J Clin Virol. 2009 Jul;45(3):179-84. BACKGROUND: Late April 2009, human infection with variant influenza virus A(H1N1)v emerged in the Northern Americas posing a threat that this virus may become the next pandemic influenza virus. OBJECTIVES: To prepare laboratories for surge capacity for molecular diagnosis of patients suspected for A(H1N1)v infection in the Netherlands. STUDY DESIGN: A panel of 10 blinded specimens containing seasonal A(H1N1) or A(H3N2), or A/Netherlands/602/2009(H1N1)

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v influenza virus, or negative control was distributed to the outbreak assistance laboratories (OAL) together with influenza virus A (M-gene), swine influenza virus A (NP-gene) and influenza virus A(H1N1)v (H1v-gene) specific primers and probes and protocol (CDC Atlanta, USA). Laboratories were asked to implement and test this protocol. RESULTS: All OAL were able to detect A(H1N1)v using the CDC M-gene reagents, the majority with similar sensitivity as the inhouse M-gene based assays. RT-PCRs used in routine diagnostic setting in the OAL specifically designed to detect H1, H3, or NS1 from seasonal influenza A viruses, did not or at very low level cross-react with A(H1N1)v. The CDC swine NP-gene and H1v-gene RT-PCRs showed somewhat reduced sensitivity compared to the CDC and in-house M-gene RT-PCRs. In contrast, in-house developed A(H1N1)v specific H1v-gene and N1v-gene RT-PCRs showed equal sensitivity to CDC and in-house M-gene RT-PCRs. CONCLUSIONS: The Dutch OAL are prepared for detection and specific identification of A(H1N1)v, although some level of crossreactivity was observed with seasonal influenza viruses. Additionally, M-gene based generic influenza A virus detection is recommended to be able to detect emerging influenza A viruses in routine settings.

PMID: 19549261 De Vries RR, Nieuwenhuijzen JA, van Tinteren H, Oddens JR, Visser O, van der Poel HG, Bex A, Meinhardt W, Horenblas S; Urological Working Group of the Amsterdam Comprehensive Cancer Center. Prostate-sparing cystectomy: long-term oncological results. BJU Int. 2009 Nov;104(9):1239-43. OBJECTIVE: To analyse the oncological outcome of prostate-sparing cystectomy (PSC). PATIENTS AND METHODS: Between 1994 and 2006, 63 men were treated with PSC after meeting the inclusion criteria (no tumour at the bladder neck, no prostate cancer). The results were compared with patients who had a standard cystoprostatectomy (SC) during the same study period, after matching for clinical and pathological characteristics. RESULTS: The 3- and 5-year disease-specific survival rates were 77% and 66% in the PSC group, and 68% and 64% in the SC group (log-rank, P = 0.6). The local recurrence rate was 7.9% and 16% for the PSC and the SC groups, respectively, and the respective distant recurrence rate was 29% and 33%. Subsequent prostate cancer was detected in 3% in the PSC group. None of these patients died from prostate cancer. In the SC group the final pathology showed that 18% had prostate cancer. CONCLUSION: Local recurrences were not diagnosed more often in the PSC than the SC group. The outcomes of both procedures are comparable with contemporary cystoprostatectomy series. We consider this procedure oncologically safe and offer this to selected patients. However, selection is the key to success, and our results should further be corroborated by the experience of others.

PMID: 19562346 Meijer RP, Gemen EF, van Onna IE, van der Linden JC, Beerlage HP, Kusters GC. The value of an artificial neural network in the decision-making for prostate biopsies. World J Urol. 2009 Oct;27(5):593-8. PURPOSE: In majority of patients who are subjected to prostate biopsies, no prostate cancer (PCa) is found. It is important to prevent unnecessary biopsies since serious complications may occur. An artificial neural network (ANN) may be able to predict the risk of the presence of PCa. METHODS: Included were all patients, who underwent transrectal ultrasound-guided prostate biopsies between June 2006 and June 2007 with a total PSA (tPSA) level between 2 and 20 microg/l. The patients were divided into two groups according to their tPSA level (2-10 microg/l and 10-20 microg/l). The ANN Prostataclass of the Universitätsklinikum Charité in Berlin was used. The predictions of the ANN were compared to the pathology results of the biopsies.


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RESULTS: Overall 165 patients were included. PCa was diagnosed in 53 patients, whereas the ANN predicted “no risk” in 19 of these patients (36%). The ANN output receiver operator characteristic (ROC) plots for the range of tPSA 2-10 microg/l and tPSA 10-20 microg/l showed an area under the curve (AUC) of 63 and 88% for the initial biopsy group, versus 69 and 57%, respectively, for the repeat biopsy group. CONCLUSIONS: The ANN resulted in a false negative rate of 36%, missing PCa in 19 patients. For use in an outpatientclinical setting, this ANN is insufficient to predict the risk of presence of PCa reliably.

PMID: 19569495 Chinnadurai SK, Troan BV, Wolf KN, DeVoe RS, Huijsmans CJ, Hermans MH, Wever PC. Septicemia, endocarditis, and cerebral infarction due to Staphylococcus aureus in a harp seal (Phoca groenlandica). J Zoo Wildl Med. 2009. 40:393. An adult, wild-collected, male harp seal (Phoca groenlandica) was transferred from a rehabilitation center to a display facility because of unilateral phthisis bulbi and decreased use of the right forelimb, which precluded its release. In quarantine, the animal demonstrated limited use of the right forelimb, which acutely progressed to complete disuse of the limb accompanied by intermittent lethargy. One month after transfer, the animal was found dead on exhibit. Necropsy showed septic arthritis of the right scapulohumeral joint, valvular endocarditis with systemic bacterial thromboembolism, and infarction of the cerebrum and myocardium. Culture of the blood and affected joint space revealed Staphylococcus aureus. Bacterial polymerase chain reaction of formalin-fixed tissues from the heart and brain were also positive for S. aureus. Staphylococcus aureus infection should be considered as an additional cause of endocarditis and embolic encephalitis in seals.

PMID: 19581668 Van Rossum LG, van Rijn AF, van Munster IP, Jansen JB, Fockens P, Laheij RJ, Dekker E. Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests. Neth J Med. 2009 May;67(5):182-6. BACKGROUND: The aim of colorectal cancer screening is to improve prognosis by the detection of early cancer and precursor stages. We compared the stage distribution of asymptomatic colorectal cancer patients detected by a positive immunochemical or guaiac-based faecal occult blood test (FOBT) with symptomatic colorectal cancer patients. METHODS: In a longitudinal cohort study tumour stages were assessed in 144 symptomatic (mean age 69.3 years, 56% male) and 41 asymptomatic colorectal cancer patients (mean age 64.9 years, 56% male) of which 11 were detected with guaiac FOBT s (G-FOBT, Hemoccult-II) and 30 with immunochemical FOBTs (I-FOBT, OCSensor). Stage distributions were used to calculate average stage specific predicted five-year survival rates and to analyse group differences with Wilcoxon log-rank test. RESULTS: Colorectal cancer was detected in significantly earlier stages in symptomatic compared with asymptomatic patients patients (p<0.0001). Average stage specific predicted five-year survival was 59.1% in symptomatic and 76.6% in asymptomatic patients. Compared with the symptomatic patients the stage distribution for colorectal cancer patients detected with Hemoccult-II was not significantly different(p=0.29), whereas colorectal cancer was detected at significantly earlier stages with the OCSensor (p<0.0001).Treatment could be confined to colonoscopy in 27% of the asymptomatic patients compared with 3% of the symptomatic patients (p<0.0001). Cancer distribution over the colon was comparable between symptomatic and asymptomatic patients (p=0.3). CONCLUSIONS: Compared with symptomatic patients,patients detected by FOBT and especially immunochemical FOBT , presented significantly more often at earlier stages suggesting increased survival. Additionally treatment could more often be confined to colonoscopy.

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PMID: 19582760 Robben SH, Sleegers MJ, Dautzenberg PL, van Bergen FS, ter Bruggen JP, Rikkert MG. Pilot study of a three-step diagnostic pathway for young and old patients with Parkinson’s disease dementia: screen, test and then diagnose. Int J Geriatr Psychiatry. 2010 Mar;25(3):258-65. OBJECTIVE: To pilot a three-step diagnostic model for young and old patients with Parkinson’s disease dementia (PDD). METHODS: Prospective investigator-blinded study. We developed a screening questionnaire for patients with Parkinson’s disease (PD) and their caregivers. Further, patients were subjected to three screening instruments (Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Addenbrooke’s Cognitive Examination-revised (ACE-R) and a detailed neuropsychological examination (NPE). Based on the NPE, patients were divided in a PD (without dementia) and a PDD-group. RESULTS: Forty-one PD patients, aged 37-94 years, participated in this study. Patients were divided in a young group, < or = 65 (n = 22) and an old group >65 years (n = 19). In the young group (PDD, n = 5) the patient-screening questionnaire predicted PDD with a sensitivity/specificity of 100.0%/94.1%; in the old group (PDD, n = 10) the proxy-screening questionnaire predicted PDD with a sensitivity/specificity of 88.9%/66.7%. In the young group, ACE-R had the largest Area Under the Curve (AUC) 0.88 (0.70-1.00), in the old group MoCA (AUC 1.00). However, the three instruments did not differ significantly. CONCLUSIONS: It seems feasible and efficient to use three consecutive diagnostic steps for PDD: (1) a screening questionnaire, (2) if positive: MoCA, FAB or ACE-R as screening instrument and (3) if positive: a detailed NPE for diagnosing PDD.

PMID: 19593191 Derijks HJ, Janknegt R, Heerdink ER, De Koning GH, Krekels M, Looij, B-J, Egberts AC. Influence of antidepressants on glycaemic control in patients with diabetes mellitus: an open label comparative study. J Clin Psychopharmacol. 2009; 29(4): 405-8. PMID: 19601985 Herbers AH, Verbruggen B, Van de Veerdonk F, Van Kraaij M, Blijlevens NM, Novakova IR. Misleading one-stage coagulation factor assay during rFVIIa treatment in lupus patient. Haemophilia. 2009 Sep;15(5):1164-6. PMID: 19622627 de Lind van Wijngaarden RF, Festen DA, Otten BJ, van Mil EG, Rotteveel J, Odink RJ, van Leeuwen M, Haring DA, Bocca G, Mieke Houdijk EC, Hokken-Koelega AC. Bone mineral density and effects of growth hormone treatment in prepubertal children with Prader-Willi syndrome: a randomized controlled trial. J Clin Endocrinol Metab. 2009 Oct;94(10):3763-71. BACKGROUND: Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. OBJECTIVES: The aim of the study was to evaluate BMD in children with PWS and to study the effects of GH treatment. DESIGN: We conducted a randomized controlled GH trial. Forty-six prepubertal children were randomized into either a GHtreated group (1.0 mg/m(2) . d) or a control group for 2 yr. At start, 6, 12, and 24 months of study, total body and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and lumbar spine bone mineral apparent density (BMAD) was calculated.


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RESULTS: Baseline total body and lumbar spine BMD sd score (SDS) were normal [mean (sd), -0.2 SDS (1.1) and -0.4 SDS (1.2), respectively]. BMADSDS, which corrects for short stature, was also normal [mean (sd), 0.40 SDS (1.1)]. Total body BMDSDS decreased during the first 6 months of GH (P < 0.0001), but increased during the second year of treatment. After 24 months of study, total body and lumbar spine BMDSDS, and the BMADSDS did not significantly differ between GH-treated children and randomized controls (P = 0.30, P = 0.44, and P = 0.47, respectively). Results were similar when corrected for body mass index SDS. Repeated measurements analysis showed a significant positive association between IGF-I SDS and total body and lumbar spine BMDSDS, but not with BMADSDS. CONCLUSIONS: Our results show that prepubertal children with PWS have a normal BMD. GH treatment had no effect on BMD, except for a temporary decrease of total body BMDSDS in the first 6 months.

PMID: 19631876 Koning OH, Kaptein BL, van der Vijver R, Dias NV, Malina M, Schalij MJ, Valstar ER, van Bockel JH. Fluoroscopic Roentgen stereophotogrammetric analysis (FRSA) to study three-dimensional stent graft dynamics. J Vasc Surg. 2009 Aug;50(2):407-12. We report the clinical feasibility of fluoroscopic Roentgen stereophotogrammetric analysis (FRSA), a validated method to quantify real time three-dimensional (3D) dynamic motion of stent grafts and the first clinical results after abdominal and thoracic endovascular repair (EVAR). Stent graft motion was measured at 30 (stereo) frames per second, during the cardiac cycle and in the patient after abdominal EVAR, due to respiratory action. Translational motions of the center of mass, diameter change, and rotational and axial motion could be measured. Quantification of 3D motion was not available until now. FRSA can provide crucial information on the forces exerted on stent grafts and will, therefore, provide essential information for improvements in stent graft design.

PMID 19643641 Jaspers JW, Kuppens SM, van Zundert AA, de Wildt MJ. Vaginal stones in a 5 year old girl: a novel approach of removal. J. Pediatrics and Adolescent Gynaecology 2010 feb: 23(1):e23-5 BACKGROUND: Primary vaginal stones in children are extremely rare and removal can be difficult. We describe a procedure for safe extraction of vaginal stones. CASE: A 5-year-old, wheelchair-bound girl was referred to the urologic department with recurrent febrile urinary tract infection. Diagnostics of the kidneys showed no abnormalities. The bladder appeared to contain two stones. On urethro-cystoscopy no stones were seen. Vaginoscopy identified vaginal stones. After 4 weeks of estrogen treatment, a second procedure via vaginal introduction of a nephroscope in combination with an ultrasonic device, effectively disintegrated the stones. SUMMARY AND CONCLUSION: We recommend the use of a nephroscope in visualizing the vagina and cervix and facilitating instrumentation in prepubertal girls.

PMID: 19692142 Scagliotti GV, Germonpré P, Bosquée L, Vansteenkiste J, Gervais R, Planchard D, Reck M, De Marinis F, Lee JS, Park K, Biesma B, Gans S, Ramlau R, Szczesna A, Makhson A, Manikhas G, Morgan B, Zhu Y, Chan KC, von Pawel J. A randomized phase II study of bortezomib and pemetrexed, in combination or alone, in patients with previously treated advanced non-small-cell lung cancer. Lung Cancer. 2010 Jun;68(3):420-6.

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BACKGROUND: This is a phase II randomized study to evaluate the efficacy and safety of bortezomib and pemetrexed alone or in combination, in patients with previously treated advanced non-small-cell lung cancer (NSCLC). The primary end point was assessment of response rate. METHODS: A total of 155 patients were randomized (1:1:1) to pemetrexed (500mg/m(2)) on day 1 plus bortezomib (1.6mg/m(2)) on days 1 and 8 (Arm A) or pemetrexed (500mg/m(2)) on day 1 (Arm B) or bortezomib (1.6mg/m(2)) on days 1 and 8 (Arm C) of a 21 day cycle. Response rate was assessed by investigators using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and toxicity assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system. RESULTS: Response rate was 7% in Arm A, 4% in Arm B, and 0% in Arm C; disease control rates were 73%, 62%, and 43%, respectively. Median overall survival was 8.6 months in Arm A, 12.7 months in Arm B, and 7.8 months in Arm C; time to progression was 4.0 months, 2.9 months, and 1.4 months, respectively. Most common reported adverse events >/=grade 3 were neutropenia (19%), thrombocytopenia (15%), and dyspnea (13%) in Arm A, neutropenia (10%) in Arm B, and dyspnea (13%) and fatigue (10%) in Arm C. CONCLUSION: In previously treated NSCLC the addition of bortezomib to pemetrexed was well tolerated but offered no statistically significant response or survival advantage versus pemetrexed alone, while bortezomib alone showed no clinically significant activity.

PMID: 19710091 Dorresteijn MJ, Draisma A, van der Hoeven JG, Pickkers P. Lipopolysaccharide-stimulated whole blood cytokine production does not predict the inflammatory response in human endotoxemia. Innate Immun. 2010 Aug;16(4):248-53. A widely applied method to study the activation of the innate immune system is in vitro stimulation of whole blood using lipopolysaccharide (LPS). However, it is unclear if in vitro cytokine production relates to in vivo cytokine levels elicited during experimental endotoxemia or sepsis. To determine the correlation between in vitro cytokine production and the in vivo inflammatory response, blood was obtained from 15 healthy volunteers for in vitro incubation with Escherichia coli LPS, immediately followed by experimental E. coli endotoxemia. Correlations of in vitro and peak in vivo cytokine concentrations were determined using Pearson correlation coefficient. In stimulated whole blood, tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta, IL-6, IL-10 and interferon (IFN)-gamma were induced to 279 +/- 53, 392 +/- 64, 5312 +/- 624, 83 +/- 20 and 343 +/- 85 pg/ml, respectively, whereas in vivo cytokine induction led to cytokine levels of 603 +/- 123, 11 +/1, 4999 +/- 1228, 167 +/- 25 and 194 +/- 40 pg/ml, respectively. Correlation coefficients between the in vitro and in vivo cytokine concentrations were for TNF-alpha, IL-1beta, IL-6, IL-10 and IFN-gamma -0.10 (P = 0.7), 0.09 (P = 0.8), 0.36 (P = 0.2), 0.19 (P = 0.5) and 0.40 (P = 0.1), respectively. Comparison between in vitro and in vivo stimulation with LPS shows no correlation between the amount of cytokines produced. In vitro cytokine production, therefore, does not predict the in vivo inflammatory response.

PMID 19713200 Clement DS, Postma G, Rothova A, Grutters JC, Prokop M, de Jong PA. Intraocular sarcoidosis: association of clinical characteristics of uveitis with positive chest high-resolution computed tomography findings. British journal of Ophthalmology 2010 Feb;94(2):219-22.


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AIM: To assess specific clinical criteria in patients with uveitis that are related to signs of sarcoidosis on high-resolution computed tomography (HRCT) of the chest. METHODS: Retrospective study of 50 consecutive patients with uveitis who were referred for chest HRCT because of suspicion of sarcoidosis. Clinical characteristics, laboratory findings, chest radiographs and chest HRCT scans were retrieved. HRCT scans were reassessed for signs of sarcoidosis. Mann-Whitney and Fisher exact test were used for data analysis. RESULTS: Ten of 50 (20%) uveitis patients referred for HRCT demonstrated signs of sarcoidosis on HRCT. The median age of these patients was significantly higher than those patients with a negative HRCT (71.1 vs 44.7 years, p=0.002). The presence of peripheral chorioretinal punched out lesions and posterior synechiae were significantly related to an abnormal HRCT scan. CONCLUSION: Increasing age, presence of peripheral multifocal chorioretinitis and posterior synechiae were associated with an abnormal HRCT scan.

PMID: 19717752 Hövels AM, Heesakkers RA, Adang EM, Barentsz JO, Jager GJ, Severens JL. Cost-effectiveness of MR lymphography for the detection of lymph node metastases in patients with prostate cancer. Radiology. 2009 Sep;252(3):729-36. PURPOSE: To apply a decision analytic model to determine whether the addition of magnetic resonance (MR) lymphography to the diagnostic workup of patients with intermediate or high probability of lymph node metastases is cost effective from a health care perspective. MATERIALS AND METHODS: The data that were used for the decision analytic model were obtained from an empiric study population of 375 patients. As the input of the decision analytic model was made given prospective patient data from several hospitals, the ethics review board of each hospital approved the study. Written consent was obtained from all patients. To investigate possible differences between strategies that utilize MR lymphography and those that do not (pelvic lymph node dissection [PLND]), two outcome measures were examined and combined in an incremental cost-effectiveness ratio (ICER) of health care resources consumed and quality-adjusted life-years (QALYs). Probabilistic and one-way sensitivity analyses were performed. RESULTS: The PLND strategy is dominated by the MR lymphography strategy. Probabilistic sensitivity analysis showed that in 63% of simulations, MR lymphography was cost saving and resulted in better patient outcome for patients with prostate cancer and intermediate or high probability of lymph node metastases. The probability of MR lymphography being inferior (more expensive and worse patient outcome) is less than 3%. CONCLUSION: MR lymphography is an efficient strategy in the detection of lymph node metastases of prostate cancer when compared with the PLND strategy.

PMID: 19718481 van Geest-Daalderop JH, Péquériaux NC, van den Besselaar AM. Variability of INR in patients on stable long-term treatment with phenprocoumon and acenocoumarol and implications for analytical quality requirements. Thromb Haemost. 2009 Sep;102(3):588-92. Within each patient treated with vitamin K antagonist (VKA), variation of the international normalised ratio (INR) occurs over the treatment period. The purpose of the present study was to assess INR variation in selected patients on long-term treatment in whom the dose of VKA was not changed. This type of variation is considered as “biological variation” which is caused by many factors but not VKA dose changes or other medication. Four groups of long-term patients were examined:

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each group with a different VKA (acenocoumarol or phenprocoumon) or a different target intensity (INR 2.0-3.5 or 2.5-4.0). All patients were monitored with the same PT system (Hepato Quick, STA-R Evolution coagulation instrument) by one laboratory. The variation of the INR within each patient was expressed as coefficient of variation (CV, in %). The CV was corrected for the average imprecision of the INR measurement (CV, 2.4%). The mean corrected CV values for the four groups were: 10.9% (acenocoumarol, target INR 2.0-3.5); 10.5% (acenocoumarol, target INR 2.5-4.0); 10.4% (phenprocoumon, target INR 2.0-3.5); 9.1% (phenprocoumon, target INR 2.5-4.0). The analytical performance goal for the INR measurement (imprecision) can be derived from the within-subject biological variation. Desirable INR imprecision goals are <4.9% and <5.3% CV for monitoring of phenprocoumon and acenocoumarol, respectively. These goals were achieved using the aforesaid PT system.

PMID: 19727754 Rutten MJ, Spaargaren GJ, van Loon T, de Waal Malefijt MC, Kiemeney LA, Jager GJ. Detection of rotator cuff tears: the value of MRI following ultrasound. Eur Radiol. 2010 Feb;20(2):450-7. OBJECTIVE: To evaluate the need for additional magnetic resonance imaging (MRI) following ultrasound (US) in patients with shoulder pain and/or disability and to compare the accuracy of both techniques for the detection of partial-thickness and fullthickness rotator cuff tears (RCT). METHODS: In 4 years, 5,216 patients underwent US by experienced musculoskeletal radiologists. Retrospectively, patient records were evaluated if MRI and surgery were performed within 5 months of US. US and MRI findings were classified into intact cuff, partial-thickness and full-thickness RCT, and were correlated with surgical findings. RESULTS: Additional MR imaging was performed in 275 (5.2%) patients. Sixty-eight patients underwent surgery within 5 months. US and MRI correctly depicted 21 (95%) and 22 (100%) of the 22 full-thickness tears, and 8 (89%) and 6 (67%) of the 9 partial-thickness tears, respectively. The differences in performance of US and MRI were not statistically significant (p = 0.15). CONCLUSIONS: MRI following routine shoulder US was requested in only 5.2% of the patients. The additional value of MRI was in detecting intra-articular lesions. In patients who underwent surgery, US and MRI yielded comparably high sensitivity for detecting full-thickness RCT. US performed better in detecting partial-thickness tears, although the difference was not significant.

PMID: 19731749 Nijboer H, Dautzenberg PL. Progressive supranucleair palsy: acetylcholineeserase-inhibitor a possible therapy? Tijdschr Gerontol Geriatr. 2009 Jun;40(3):133-7. Progressive supranucleair palsy (PSP) is a serious neurologic disease which is seldom diagnosed due to its complexity. In 1996 international diagnostic criteria were developed by a group of experts, the diagnosis remains complicated. We describe three cases, which were followed in the period 2001-2008. In these case reports we elaborate on the therapeutic use of rivastigmine. During off-label rivastigmine use, patients showed minimal further cognitive decline, specifically with respect to frontal defects. However, larger studies and trials are necessary to explore the effects of rivastigmine in patients with PSP.

PMID: 19733556 de With MC, van der Heijden EP, van Oosterhout MF, Kon M, Kroese AB. Contractile and morphological properties of hamster retractor muscle following 16 h of cold preservation. Cryobiology. 2009 Dec;59(3):308-16. INTRODUCTION: Cold hypoxia is a common factor in cold tissue preservation and mammalian hibernation. The purpose of


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this study was to determine the effects of cold preservation on the function of the retractor (RET) muscle of the hamster in the non-hibernating state and compare these with previously published data (van der Heijden et al., 2000) on the rat cutaneus trunci (CT) muscle. MATERIALS AND METHODS: After cold storage (16 h at 4 degrees C), muscles were stimulated electrically to measure maximum tetanus tension (P(0)) and histologically analyzed. The protective effects of addition of the antioxidants trolox and deferiprone and the calcium release inhibitor BDM to the storage fluid were determined. RESULTS: After storage, the twitch threshold current was increased (from 60 to 500 microA) and P(0) was decreased to 27% of control. RET morphology remained unaffected. RET muscle function was protected by trolox and deferiprone (P(0), resp., 43% and 59% of control). Addition of BDM had no effect on the RET. CONCLUSIONS: The observed effects of cold preservation and of trolox and deferiprone on the RET were comparable to those on CT muscle function, as reported in a previously published study (van der Heijden et al., 2000). Both hamster RET and rat CT muscles show considerable functional damage due to actions of reactive oxygen species. In contrast to the CT, in the RET cold preservation-induced functional injury could not be prevented by BDM and was not accompanied by morphological damage such as necrosis and edema. This suggests that the RET myocytes possess a specific adaptation to withstand the Ca(2+) overload induced by cold ischemia.

PMID: 19733956 Penninx J, Brandes M, de Bruin JP, Schneeberger PM, Hamilton CJ. Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests. Eur J Obstet Gynecol Reprod Biol. 2009 Dec;147(2):178-82. OBJECTIVES: Chlamydia antibody test (CAT) has been proposed to predict tubal disease. A correlation between CA-125 and the extent of endometriosis has been found by others. In this study we explored whether a combination of the two tests adds to the predictive value of the individual tests for predicting tubal disease or endometriosis. We also used the combination of tests as a new index test to screen for severe pelvic pathology. STUDY DESIGN: This retrospective study compares the findings of 240 laparoscopies with the serological test results. Findings were classified according to the existing ASRM scoring systems for adnexal adhesions, distal tubal occlusion and endometriosis. Severe pelvic pathology was defined as the presence of ASRM classes III and IV tubal disease or ASRM classes III and IV endometriosis. The predictive value was calculated for both tests separately and for the combined test. The combined test was positive if at least one test result was abnormal (CAT positive and/or CA-125 > or =35 IU/ml). RESULTS: 67/240 women had tubal disease, 81/240 had some degree of endometriosis. The odds ratios (ORs) of the CAT and the combined test to diagnose severe tubal disease were 6.6 (2.6-17.0) and 7.3 (2.9-19.3), respectively. The ORs of the CA-125 and the combined test to diagnose severe endometriosis were 15.6 (6.2-40.2) and 3.0 (1.2-8.0), respectively. Severe pelvic pathology was present in 65/240 women (27%). The ORs for severe pelvic pathology of the CAT, CA-125 and the combined test were 2.5 (1.4-5.3), 4.9 (1.9-9.6) and 6.6 (3.3-13.4), respectively. If the combined test was normal 15 out 131 women (11%) were shown to have severe pelvic pathology. CONCLUSIONS: The combined test adds hardly anything to the predictive value of CAT alone to diagnose severe tubal disease. The combined test is better than the CAT to predict severe pelvic pathology, but is not significantly better than the CA-125. If both the CAT and CA-125 are normal one could consider not performing a laparoscopy.

PMID: 19757757 van Poppel PC, Stehouwer CD, Beutler JJ, Korst MB, Beerlage HP, Hoogeveen EK. Hyperchloremic metabolic acidosis in a patient with an ureteroileostomy according to Bricker. Ned Tijdschr Geneeskd. 2009 May 23;153(21):1024-8.

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PMID: 19771542 Dautzenberg PL, van der Zande JA, Conemans JM, Rikkert MG. Off-label drug use on a Dutch geriatric ward. Int J Geriatr Psychiatry. 2009 Oct;24(10):1173-4. PMID: 19778289 De Wit NC, de Jager CP, Meekelenkamp JC, Schoorl M, van Gageldonk-Lafeber AB, Leenders AC, Kusters R, Wever PC. Markers of infection in inpatients and outpatients with acute Q-fever. Clin Chem Lab Med. 2009;47(11):1407-9. BACKGROUND: Query-fever (Q-fever) is a zoonotic infection caused by the intracellular Gram-negative coccobacillus Coxiella burnetii. A large ongoing outbreak of Q-fever has been reported in the Netherlands. We studied various markers of infection in inpatients (hospitalised) and outpatients (treated by a general physician) with acute Q-fever in relation to disease severity. METHODS: Leukocyte counts, C-reactive protein (CRP) and procalcitonin (PCT) concentrations were measured in 25 inpatients and 40 outpatients upon presentation with acute Q-fever. Chest X-rays, if available, were analysed and confusion, urea, respiratory rate, blood pressure-age 65 (CURB-65) scores, indicating severity of pneumonia, were calculated. RESULTS: CRP was the only marker that significantly differentiated between inpatients and outpatients. It was increased in all patients from both groups. Leukocyte counts and PCT concentrations did not differ between inpatients and outpatients. Overall, only 13/65 patients had an increased leukocyte count and only 11/65 patients presented with PCT concentrations indicative of possible bacterial respiratory tract infection. Infiltrative changes on the chest X-ray were observed in the majority of patients. CURB-65 score was 0+/-1 (mean+/-SD). CONCLUSIONS: Acute Q-fever, a relatively mild pneumonia with low CURB-65 scores, specifically induces a response in CRP, while PCT concentrations and leukocytes are within the normal range or increased only marginally.

PMID: 19783833 Brandes M, van der Steen JO, Bokdam SB, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. When and why do subfertile couples discontinue their fertility care? A longitudinal cohort study in a secondary care subfertility population. Hum Reprod. 2009 Dec;24(12):3127-35. BACKGROUND: A substantial number of subfertile couples discontinues fertility care before achieving pregnancy. Most studies on dropouts are related to IVF. The aim here is to examine dropout rates at all stages of fertility care. METHODS: We analysed a consecutive cohort of 1391 couples, referred to our secondary care hospital between January 2002 and December 2006. Discontinuation rates were studied at six stages. Stage I: immediately after first visit, Stage II: during diagnostic workup, Stage III: after finishing diagnostic workup but before treatment, Stage IV: during or after non-IVF treatment, Stage V: during IVF, Stage VI: after at least 3 cycles of IVF. Reasons to discontinue and spontaneous pregnancy rates after discontinuation were secondary outcomes. RESULTS: In our cohort 319 couples dropped out of fertility care, 76.8%, [95% confidence interval (CI): 72.2-81.4] on their own initiative and 23.2% (95% CI: 18.6-27.8) on doctor’s advice. Percentage (95% CI) of couples discontinuing per stage were: Stage I 6.0% (3.4-8.6), Stage II 3.4% (1.5-5.5), Stage III 35.7% (30.5-41.0), Stage IV 23.5% (18.9-28.2), Stage V 17.9% (13.7-22.1) and Stage VI 13.5% (9.7-17.2). Main reasons for dropout (%, 95% CI) were ‘emotional distress’ (22.3%, 17.726.8), ‘poor prognosis’ (18.8%, 14.5-23.1) and ‘reject treatment’ (17.2%, 13.1-21.4). The spontaneous ongoing pregnancy


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rate after discontinuation was 10% (6.7-13.3). CONCLUSION: About half of the couples stopped before any fertility treatment was started and one-third stopped after at least one IVF cycle. The main reasons for withdrawal were emotional distress and poor prognosis. This insight may help to improve quality of patient care by making care more responsive to the needs and expectations of subfertile couples.

PMID: 19785897 Keijsers CJ, Custers EJ, ten Cate OT. A new, problem oriented medicine curriculum in Utrecht: less basic science knowledge. Ned Tijdschr Geneeskd. 2009;153:B400. OBJECTIVE: To investigate whether the transition from a conventional, discipline-based curriculum to a problem-orientated, integrated curriculum at the University Medical Center Utrecht, the Netherlands, has resulted in students having less knowledge of the basic medical sciences. DESIGN: Comparative. METHOD: The difference in the amount of basic science between the curricula was quantitatively assessed. 37 final-year students in each curriculum volunteered to complete a test specifically designed to measure knowledge of the basic sciences, a few weeks before their graduation. RESULTS: The transition from the old to the new curriculum resulted in a decline of almost half in the amount of time dedicated to the basic sciences, from 84 to 48 ‘fulltime week equivalents’. Students in the old curriculum performed significantly better on the test than students in the new curriculum, with 43.2% (SD: 9.56) correct answers versus 35.8% (SD: 8.19) correct answers respectively, which amounted to an effect size of 0.828 (Cohen-d). Yet, on the pathophysiology/pathology subscale, students in each curriculum showed similar performance: 36.1% (SD: 11.55) correct answers for students in the old curriculum, versus 37.2% (SD: 11.66) correct answers for students in the new curriculum. CONCLUSION: Students in the old curriculum had overall significantly more knowledge of the basic sciences than students in the new curriculum, except for pathophysiology/pathology, though the time devoted to this discipline in the new curriculum had also decreased considerably.

PMID: 19785899 van Poppel PC, Stehouwer CD, Beutler JJ, Korst MB, Beerlage HP, Hoogeveen EK. Hyperchloremic metabolic acidosis in a patient with an ureteroileostomy according to Bricker. Ned Tijdschr Geneeskd. 2009;153:B317. A 79-year-old male with a Bricker loop and chronic renal failure was admitted to hospital because progressive dyspnoea. This was due to severe hyperchloraemic metabolic acidosis. Hyperchloraemic acidosis can occur if urinary diversions are constructed from the colon or ileum. Contact between intestinal mucosa and urine may cause reabsorption of ammonium and chloride, and secretion of bicarbonate. Hyperchloraemic acidosis is rarely seen with an incontinent ileal loop due to its small absorbing surface area and the rapid drainage of urine from the loop. Hyperchloraemic acidosis in a patient with a Bricker loop may point to prolonged contact between the ileum and urine. A loopogram is necessary to investigate the cause. In our patient the loopogram showed that the incorporated bowel segment was too long. After shortening of the Bricker loop, the patient recovered from the hyperchloraemic metabolic acidosis.

PMID: 19811904 van Herk-Sukel MP, van de Pll-Franse LV, Lemmens VE, Vreugdenhil G, Pruijt JF, Coebergh JW, Herings RM. New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry

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and the PHARMO Record Linkage System. Eur J Cancer 2010;46:395-404. BACKGROUND: Insight into co-morbidity and treatment effects is pivotal to improve quality of care for cancer patients. OBJECTIVES: To determine whether linkage of the Eindhoven Cancer Registry (ECR) and the PHARMO Record Linkage System (RLS) was technically feasible and to assess which patient-centric data would result from this linkage. METHODS: The ECR records data on tumour stage and primary treatment of all newly diagnosed cancer patients in the southeastern Netherlands including co-morbidity at diagnosis, whereas the PHARMO RLS includes data from multiple linked observational databases such as data on drug utilisation (for both in- and out-patients, including chemotherapy), hospitalisations and clinical laboratory measurements. All patients who lived or had been living in the overlapping area served by the ECR and the PHARMO RLS during 1998-2006 were selected for linkage which was performed with probabilistic medical record linkage. RESULTS: The linkage resulted in an ECR-PHARMO cohort of 40,004 cancer patients with a total of 42,767 primary tumours. The cancer patients in the linked ECR-PHARMO cohort were representatives for the cancer patients included in the total ECR during 1998-2006. Cancer patients included in the cohorts had a mean history of 5 years and a mean follow-up ranging from 2 to more than 4 years (dependent on the survival rate of the specific cancer type). CONCLUSIONS: Linkage of ECR and the PHARMO RLS creates the possibility to study patient-centric drug utilisation, health resources utilisation and their costs, in addition to the effectiveness and safety of pharmaceuticals in routine daily practice in cancer patients.

PMID: 19818177 Van Wensen RJA, Bosscha K, Jager GJ, van der Linden JC, Fijnheer R. An invasive process in the pancreas: sometimes lymphoma. (Een ruimteinnemend proces in het pancreas. Niet altijd een carcinoom.) Ned Tijdschr Geneeskd. 2009;153:B164. An invasive process in the pancreas was found in a 60-year-old woman and a 50-year-old man with abdominal symptoms. Generally, such findings turn out to be adenocarcinoma. However, these patients had lymphoma. Primary pancreatic lymphoma or localization of lymphoma in the pancreas are rare and chemotherapy may be curative. Therefore, obtaining tissue for histopathological confirmation of the diagnosis is very important. Both patients underwent chemotherapy. The first patient was in complete remission one month after the last chemotherapy cycle. In the second, the disease went into remission, but he suddenly died of sepsis after the fourth chemotherapy cycle.

PMID: 19837938 de Lind van Wijngaarden RF, Siemensma EP, Festen DA, Otten BJ, van Mil EG, Rotteveel J, Odink RJ, Bindels-de Heus GC, van Leeuwen M, Haring DA, Bocca G, Houdijk EC, Hoorweg-Nijman JJ, Vreuls RC, Jira PE, van Trotsenburg AS, Bakker B, Schroor EJ, Pilon JW, Wit JM, Drop SL, Hokken-Koelega AC. Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome. J Clin Endocrinol Metab. 2009 Nov;94(11):4205-15. BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Shortterm GH treatment has beneficial effects. OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters.


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SETTING: We conducted a multicenter prospective trial. DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGFI/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

PMID: 19841489 Van Kuilenburg JT, van Niekerk J, Sinnige H, de Jager CP. A woman with a swollen neck. Neth J Med. 2009 Oct;67(9):308-9. PMID: 19847397 Simons KS, Pickkers PP, Oyen WJG van der Hoeven JG. F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected of infection. Intensive Care Med. 2010 Mar;36(3):504-11. PURPOSE: To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS: FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS: Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS: FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues.

PMID: 19854713 Hartkamp A, Geenen R, Godaert GL, Bijl M, Bijlsma JW, Derksen RH. Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent

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systemic lupus erythematosus: a randomised controlled trial. Ann Rheum Dis. 2010 Jun;69(6):1144-7. OBJECTIVE: Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE. METHODS: In a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment. RESULTS: Patients from the DHEA and placebo group improved on general fatigue (p<0.001) and mental well-being (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p=0.04). CONCLUSIONS: The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE.

PMID: 19855108 Brandes M, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA. The relative contribution of IVF to the total ongoing pregnancy rate in a subfertile cohort. Hum Reprod. 2010 Jan;25(1):118-26. BACKGROUND: Although in vitro fertilization (IVF) was introduced more than 30 years ago, its exact role in the spectrum of fertility treatments has never been studied in an unselected population. The aim of this study was to visualize the contribution of IVF to the ongoing pregnancy rates in a cohort of newly referred subfertile couples. MATERIALS: All new subfertile couples (n = 1391) that were referred to our fertility clinic by their general practitioner between January 2002 and December 2006 were included. Fertility care was provided according to the national Dutch fertility guidelines. Data on diagnosis, treatment, mode of conception and pregnancy outcome were documented. If followup data were missing, couples were contacted. Cumulative pregnancy curves were constructed for the whole cohort and per diagnostic group. RESULTS: As per December 2008 the overall ongoing pregnancy rate was 72.0% (n = 1001). Almost half of the pregnancies were conceived spontaneously (45.6%), 19.2% after ovulation induction (OI), 14.0% after intrauterine insemination (IUI) and 21.2% after IVF. A quarter (n = 349) of couples received IVF treatment, which was successful in 60% of cases. IVF had the largest contribution to ongoing pregnancies in patients with ‘tubal factor’, ‘endometriosis’ and ‘male factor’ (45, 45 and 37%, respectively) while in couples with ‘unexplained subfertility’ and ‘ovulation disorders’ the contribution to ongoing pregnancies of IVF was limited (13 and 4.5%, respectively). CONCLUSIONS: In a cohort of subfertile couples, most pregnancies were conceived spontaneously. The contribution of IVF to ongoing pregnancy rates was comparable to those of OI and IUI. Compared with the pre-IVF era, couples with ‘endometriosis’, ‘tubal factor’ and ‘male subfertility’ have benefited most from its introduction.

PMID: 19857286 Hermans MH, Poodt J, van Geest-Daalderop JH, Péquériaux NC, Conemans JM. Resistance to coumarin derivatives due to mutated vitamin-K enzyme. Ned Tijdschr Geneeskd. 2009;153:A691.


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In 2006 a case report was published in this journal describing partial acenocoumarol- and phenprocoumon resistance in a 78-year-old man. A mutation in the VKORC1 gene was suggested to be the cause of the observed resistance. We examined the patient and found a new and hitherto unknown mutation in the VKORC1 gene which may well explain the observed resistance. The mutation concerns a polymorphism in exon 2 that predicts the substitution of tryptophan at position 59 of the VKOR protein by arginine, the p.Trp59Arg mutation. Meanwhile, we have detected the same p.Trp59Arg mutation in another patient with coumarin derivative resistance. The fact that this mutation did not occur in 100 individuals who responded well to coumarin derivatives, together with the knowledge that amino acid 59 is conserved among species, renders it likely that p.Trp59Arg was the cause of the partial acenocoumarol- and phenprocoumon resistance observed in these two patients.

PMID: 19864365 Van Wijk PT, Schneeberger PM, Heimeriks K, Boland GJ, Karagiannis I, Geraedts J, Ruijs WL. Occupational blood exposure accidents in the Netherlands. Eur J Public Health. 2010 Jun;20(3):281-7. BACKGROUND: To make proper evaluation of prevention policies possible, data on the incidence and associated medical costs of occupational blood exposure accidents in the Netherlands are needed. METHODS: Descriptive analysis of blood exposure accidents and risk estimates for occupational groups. Costs of handling accidents were calculated. RESULTS: Each year, an estimated 13,000-15,000 blood exposure accidents are reported in the Netherlands, 95% in occupational settings. Hepatitis B (HBV) vaccination is offered free of charge only to people in risk groups, the seroprevalence of HBV, hepatitis C (HCV) and human immunodeficiency virus (HIV) is low and few infections are related to blood exposure accidents. High-risk accidents occur mainly in hospitals. In nursing homes and home care settings, the majority of the accidents are low-risk. Limited data are available about occurrence of accidents in other occupational groups. Associated medical costs from occupational blood exposure accidents are mainly determined by the initial risk management. CONCLUSIONS: Accidents must be managed effectively to prevent infection and reduce anxiety in injured employees. While strategies to reduce HCV and HIV infection should be primarily aimed at reducing the occurrence of high-risk accidents, vaccination can prevent HBV infection and cut the costs of handling low-risk accidents. The implementation of vaccination strategies, safe working policies and the proper use of safe equipment should be monitored better.

PMID: 19864666 Tieleman AA, den Broeder AA, van de Logt AE, van Engelen BG. Strong association between myotonic dystrophy type 2 and autoimmune diseases. J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1293-5. BACKGROUND: Myotonic dystrophy type 2 (DM2) is a dominantly inherited multisystem disorder, characterised by progressive proximal weakness, myotonia, cataracts and cardiac conduction abnormalities. Our clinical impression of an association between DM2 and autoimmune diseases or autoantibody formation has not been published previously. OBJECTIVE: The aim of the present study was to investigate the frequency of autoimmune diseases and serum autoantibodies in patients with DM2 compared with patients with adult onset myotonic dystrophy type 1 (DM1). METHODS: 28 genetically proven Dutch DM2 patients participated in the study and were compared with 51 age and sex matched adult onset DM1 patients. As the primary outcome measure, the presence of an autoantibody or autoreactive T cell associated autoimmune disorder was assessed. As a secondary outcome measure, the presence of autoantibodies in serum (nuclear and non-nuclear antibodies) was assessed in all patients. RESULTS: The frequency of autoimmune diseases (21% vs 2%) and the frequency of autoantibodies (25% vs 2%) were both

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significantly (p<0.01) higher in DM2 patients compared with DM1 patients. Data on DM1 patients were comparable with the general population. Results were not confounded by smoking, medication use, familial clustering, age or sex. CONCLUSION: The results provide new insight into the clinical picture of DM2. In addition, possible explanations for the association between DM2 and autoimmune diseases are proposed.

PMID: 19875752 Van Nes JG, Seynaeve C, Maartense E, Roumen RM, de Jong RS, Beex LV, Meershoek-Klein Kranenbarg WM, Putter H, Nortier JW, Van de Velde CJ; Cooperating investigators of the Dutch TEAM trial (Bosscha K). Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Ann Oncol. 2010 May;21(5):974-82. BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. METHODS: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. RESULTS: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). DISCUSSION: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.

PMID: 19875991 Vink EE, van Coeverden SC, van Mil EG, Felius BA, van Leerdam FJ, Delemarre-van de Waal HA. Changes and tracking of fat mass in pubertal girls. Obesity (Silver Spring). 2010 Jun;18(6):1247-51. Puberty is a critical period in body composition development. The influence of puberty on the development of fat mass asks for further investigation. We investigated the development of fat mass during puberty in a longitudinal prospective study in 152 healthy nonobese white girls, initial ages between 9 to 12 years. The influence of menarcheal age and the existing of tracking of fat mass have been analyzed. In 10 years time, participants were measured on eight time points. Various anthropometric data were collected, breast development was staged according to Tanner and body composition was determined with the dual-energy X-ray absorptiometry (DXA) scan. Calculations were made with the use of a linear mixed model. Fat mass increases from 7.9 kg (23.6%) at B1 to 18.5 kg (29.3%) at B5. Fat mass is higher in girls with an early menarche than in girls with a late menarche from B2. Girls in the quartile with initially the lowest fat mass have a chance of being in the same quartile after 10 years of 77% (P < 0.001). Girls in the quartile with initially the highest fat mass, have a risk of staying in the highest quartile of 55% (P < 0.001). Menarcheal age is of great influence on the development of fat mass. Girls with an early menarche, will have a bigger fat mass, especially at the end of puberty. Tracking of fat mass exists: a high amount of fat mass in early puberty will continue to exist at young adulthood.


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PMID: 19880434 van Steenbergen LN, Rutten HJ, Creemers GJ, Pruijt JF, Coebergh JW, Lemmens VE. Large age and hospital-dependent variation in administration of adjuvant chemotherapy for stage III colon cancer in southern Netherlands. Ann Oncol. 2010 Jun;21(6):1273-8. BACKGROUND: The purpose was to assess factors associated with the administration of chemotherapy and their relation to survival at a population-based level. METHODS: All patients diagnosed with primary colon cancer stage III from 2001 to 2007 in the area of the Eindhoven Cancer Registry were included (N = 1637). We examined determinants of the administration of adjuvant chemotherapy and their relation to survival. RESULTS: The proportion of patients receiving adjuvant chemotherapy decreased with increasing age from 85% for patients <65 years to 68% for those 65-74 years and 17% for patients > or =75 years, with large interhospital variation. Elderly patients {odds ratio (OR) 0.1 [95% confidence interval (CI) 0.1-0.1]} and those with comorbidity [OR 0.6 (95% CI 0.5-0.8)] received adjuvant chemotherapy less often. Patients with an intermediate [OR 1.4 (95% CI 1.1-1.9)] or high socioeconomic status [OR 1.5 (95% CI 1.1-2.0)] or stage IIIC [OR 1.5 (95% CI 1.1-2.0)] received adjuvant chemotherapy more often. Adjuvant chemotherapy was the most important predictor of survival. In a multivariable analysis, older age was no longer a significant negative predictor of survival, in contrast to comorbidity, higher tumor stage, poor tumor grade, and male gender. The improvement in survival from 2001 to 2006 did not reach statistical significance. CONCLUSION: Adherence to guidelines for adjuvant chemotherapy was still suboptimal in 2007, especially for elderly patients, and differed widely between hospitals.

PMID: 19880501 Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian HematoOncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive highdose melphalan, 200 mg/m(2), followed by maintenance with alpha-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse.

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PMID: 19898738 Faraj D, Ruurda JP, Olsman JG, van Geffen HJ. Five-year results of inguinal hernia treatment with the Prolene Hernia System in a regional training hospital. Hernia. 2010 Apr;14(2):155-8. PURPOSE: Long-term results of inguinal hernia repair with the Prolene Hernia System (PHS) in our regional training hospital were retrospectively analysed. Research was conducted in an identical cohort of patients previously investigated for short-term results. METHODS: One-hundred and fifty-eight patients (217 inguinal hernias) treated with the PHS were traced and included. Patients were invited to visit the outpatient clinic for a brief history, physical examination and ultrasound. A quality of life questionnaire was completed by all patients. The primary endpoint was recurrence rate. Testis atrophy, chronic pain and hypaesthesia were secondary endpoints. RESULTS: The mean age of the population (n = 187) was 62.2 years (range 28-92), with a male:female ratio of 15:1 (175:12). The median follow-up was 5.5 years (range 3.9-6.8). One-hundred and forty-five patients visited the outpatient clinic, while 13 patients were included by telephone interview. Twenty-one patients died during follow-up and eight others were lost to follow-up. The resulting follow-up rate was 85% (158/187). In our initial study, we found four recurrences (1.8%) and seven patients with persisting pain (3.2%) after 32 months. During current follow-up, five patients were diagnosed with recurrent herniation (2.3%, 5/217) and only four patients (1.8%) suffered from persisting pain. Three patients (1.4%) were diagnosed with testicular atrophy, while ten patients (4.4%) experienced hypaesthesia. CONCLUSION: In a regional training hospital, the recurrence rate and long-term complications of patients treated for inguinal hernia with the PHS are acceptable after a follow-up of 5.5 years. The number of patients experiencing persistent pain seems to decrease over time.

PMID: 19900138 De Reu PA, van Diem MT, Eskes M, Oosterbaan HP, Smits LJ, Merkus JM, Nijhuis JG. The Dutch Perinatal Audit Project: a feasibility study for nationwide perinatal audit in the Netherlands. Acta Obstet Gynec Scand. 2009;88(11):1201-8. OBJECTIVE: To investigate the feasibility of nationwide perinatal mortality audits in the Netherlands. STUDY DESIGN: Over a one-year period, data for all cases of perinatal mortality were collected. Six perinatal audit panels of professionals within perinatal care investigated and classified causes of death and identified the presence of substandard care factors (SSF). RESULTS: Out of 22,189 newborns, 228 cases of perinatal mortality were audited. Placental pathology, congenital anomalies and preterm birth were the main causes of perinatal death. SSF by caregivers were identified in 72 cases (32 %). Almost 20% of the cases were not reported. CONCLUSIONS: In the Netherlands, perinatal audit is well supported by all groups of caregivers. It reveals usable facts and findings for the quality assessment of perinatal care. This audit showed that in 9% of the cases perinatal death was related to SSF and potentially avoidable. However, immediate reporting of cases of perinatal death apart from regular registration in the perinatal database proved to be inaccurate. Once a nationwide audit program is realized, in which data from the different caregivers will be collected in a single database instead of collection by linkage afterwards, this problem should be solved. Local audits will start from 2009. These audits will assess mortality cases within their respective areas and may initiate adjustments for perinatal care and optimize the quality of care and inter-professional collaboration. Yearly nationwide audits will focus on specific items (e.g. term or post-term deliveries) and may well offer an opportunity for the development or adjustment of national guidelines.


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PMID: 19900320 Schouten HW, Knippels MC, Franken RJ. Maggots in the wound, debridement, disinfection and wound healing. Ned Tijdschr Geneeskd. 2009;153:A624. An 87-year-old man had a longstanding untreated large basosquamous carcinoma on his right ear. He was admitted to the emergency department at our hospital. A large portion of the auricle had perished, together with part of the tumour. Surgery was planned but two days before, the patient complained of an irritating loud noise in his ear. We discovered this was caused by maggots in his external acoustic meatus: myiasis. Dozens of maggots were removed. A striking finding was that the smell of the wound had disappeared and that the wound was much cleaner, with a reddish aspect and less necrosis. The surgical procedure was uneventful. Larval therapy has been known for centuries. In recent years it has gained renewed interest as it may enhance wound debridement, wound disinfection, and may promote wound healing.

PMID: 19913419 Lammers EJ, Huibers P, van der Sangen MJ, van de Poll-Franse LV, Poortmans PM, Ernst MF, Lemaire BM, Meijs CM, Nuytinck HK, Voogd AC. Factors contributing to improved local control after mastectomy in patients with breast cancer aged 40 years or younger. Breast. 2010 Feb;19(1):44-9. Long-term local control rates were studied in a series of 659 patients with invasive breast cancer aged 40 years or younger, who underwent mastectomy in general hospitals in the southern part of the Netherlands between 1988 and 2005. During a median follow-up time of 6.0 years, 34 patients developed a local recurrence in the chest wall without previous or simultaneous evidence of distant disease. The 5- and 10-year actuarial local recurrence rates for the total group were 5.6% (95% confidence interval [95% CI], 3.5-7.7%) and 7.3% (95% CI, 4.7-9.9%), respectively. A multivariate analysis showed that patients receiving radiotherapy (hazards ratio [HR], 0.29; 95% CI, 0.10-0.96) or adjuvant systemic treatment (HR 0.23; 95% CI, 0.08-0.65) had a significantly lower risk of local recurrence. It is concluded that excellent local control rates can be obtained with mastectomy in young women with breast cancer, especially in those who receive adjuvant systemic treatment and/or radiotherapy.

PMID: 19915839 Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, Oyen WJ, Kotzerke J, Hoekstra OS, Pruim J, Marsden PK, Tatsch K, Hoekstra CJ, Visser EP, Arends B, Verzijlbergen FJ, Zijlstra JM, Comans EF, Lammertsma AA, Paans AM, Willemsen AT, Beyer T, Bockisch A, Schaefer-Prokop C, Delbeke D, Baum RP, Chiti A, Krause BJ. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010 Jan;37(1):181-200. The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/ CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.

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PMID: 19921303 Jongen PJ, Sindic C, Carton H, Zwanikken C, Lemmens W, Borm G; Functional composite and quality of Life in Avonex-treated Relapsing multiple sclerosis patients study group. Anten, Driessen, Baard, Frequin, Hintzen, Hupperts, Jongen, Linssen, MispelblomBeyer, Moll, van Munster, Pratzsky, Sanders, Smits, van Walbeek, Willems, Witjes, van Zuilen, Bartholomé, Braeckveldt, Van der Motte, Debruyne, Decoo, Dedeyn, Engelborghs, Dupuis, Jacquerye, Van de Gaer, Guillaume, Reznik, Harmant, D’Hooghe, Klippel, Willems, van Landegem, Strauven, Maertens de Noordhout, Delavaux, Nagels, Seeldrayers, Vervonck, Sindic, Goffette, El-Memar, Hawkins, de Diego. Improvement of health-related quality of life in relapsing remitting multiple sclerosis patients after 2 years of treatment with intramuscular interferon-beta-1a. J Neurol. 2010 Apr;257(4):584-9. In patients with relapsing remitting multiple sclerosis (RRMS), the effect of interferon-beta (INFb) on health-related quality of life (HR-QoL) is not firmly documented. The objective of this study is to assess HR-QoL during 2 years of treatment with intramuscular INFb and its correlation with disability. In 36 neurological practices in the Netherlands (17), Belgium (16), United Kingdom (2) and Luxemburg (1), 284 RRMS patients were treated with intramuscular INFb1a. Physical and mental domains of HR-QoL were measured by the MS54 Quality of Life (MS54QoL) questionnaire, and disability was assessed by the Multiple Sclerosis Functional Composite (MSFC) (Timed 25-Foot Walk Test [Timed 25-FWT], 9 Hole Peg Test [9-HPT], Paced Auditory Serial Addition Test [PASAT]) at baseline and at months 3, 6, 12, 18 and 24. Expanded Disability Status Scale (EDSS) score was assessed at baseline and month 24. Pearson’s correlation coefficients were determined and predefined factors were analyzed for relation to HR-QoL after baseline by stepwise regression analyses on physical and mental scores. 204 patients (71.8%) completed 2 years of treatment. Mean values for MS54QoL increased from 56.6 to 61.0 for physical (p < 0.05) and from 57.2 to 61.1 for mental domain (p = 0.07). Correlations between physical domain and MSFC was -0.40 (p < 0.05), and between mental domain and MSFC -0.24 (p < 0.05). MSFC and EDSS did not change. Increase of physical MS54QoL was associated with lower age, lower EDSS, less time for Timed 25-FWT, and higher PASAT score at baseline. Increase of mental MS54QoL was associated with higher PASAT and lower EDSS. Patients who discontinued INFb had lower physical or mental HR-QoL at baseline. In RRMS patients, 2 years of treatment with intramuscular INFb-1a is associated with an increase in HR-QoL, especially in younger patients with low disability.

PMID: 19923824 Koebrugge B, Bosscha K, Ernst MF. Transanal endoscopic microsurgery for local excision of rectal lesions: is there a learning curve? Dig Surg. 2009;26(5):372-7. BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive technique for the local resection of benign and stage T1 rectal lesions in selected patients, associated with lower morbidity and mortality rates than open surgery. We present our initial results and assess whether experience influences outcome after TEM. METHODS: This was a prospective descriptive survey. All patients undergoing TEM for tubulovillous adenoma or carcinoma between 2002 and 2007 were included. RESULTS: A total of 105 patients were included. Median age was 68 years. Median distance of the lesion from the anal verge was 7.0 cm; median operating time was 90 min. In 10 patients, the peritoneum was opened. Six procedures were converted to (low) anterior resections. Postoperative staging revealed 77 tubulovillous adenomas, 22 stage T1, 5 stage T2 and 1 stage T3 carcinomas; tumor resection was radical in 86%. The postoperative complication rate was


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7.6%. Length of hospital stay, operating time and complications significantly diminished over time. After a median follow-up of 27 months, 8 recurrences occurred (7.6%). CONCLUSION: TEM is a safe technique with low morbidity and recurrence rates. Over time, experience leads to a reduction in operation time, length of patients’ hospital stay and complication rate. TEM remains the treatment of choice for benign lesions and stage T1 rectal carcinomas in selected patients.

PMID: 19930740 Mattheij M, van der Weij AM. A girl with recurrent swelling of the parotis region. Ned Tijdschr Geneesk. 2009;153-A188. PMID: 19941334 Bernsen RA, de Jager AE, Kuijer W, van der Meche FG, Suurmeijer TP. Psychosocial dysfunction in the first year after Guillain-Barre syndrome. Muscle Nerve 2010 Apr;41(4):533-9. In this investigation we study the impact of Guillain-Barré syndrome (GBS) on psychological distress, depressive symptoms, and health status of patients during the first year after GBS. At 3, 6, and 12 months, patients were given the General Health Questionnaire, the Sickness Impact Profile, and the Center for Epidemiologic Studies Depression Scale. Eighty-five patients participated. Psychological distress and depressive symptoms were present but improved between 3 and 6 months. At 12 months the psychosocial health status was still impaired. Patients who perceived their physical residua to be moderately to seriously disruptive and patients with muscle ache and cramps had worse scores on all scales. It can be concluded that most of the improvement occurred in the first 6 months. Psychosocial health status, however, was still impaired at 1 year, but depressive symptoms played no role. Treatment of muscle ache and cramps, and the disruptive effect of physical residua should be seriously considered.

PMID: 19959398 Munneke M, Nijkrake MJ, Keus SH, Kwakkel G, Berendse HW, Roos RA, Borm GF, Adang EM, Overeem S, Bloem BR; ParkinsonNet Trial Study Group.(ter Bruggen JP) Efficacy of community-based physiotherapy networks for patients with Parkinson’s disease: a clusterrandomised trial. Lancet Neurol. 2010 Jan;9(1):46-54. BACKGROUND: Many patients with Parkinson’s disease are treated with physiotherapy. We have developed a communitybased professional network (ParkinsonNet) that involves training of a selected number of expert physiotherapists to work according to evidence-based recommendations, and structured referrals to these trained physiotherapists to increase the numbers of patients they treat. We aimed to assess the efficacy of this approach for improving health-care outcomes. METHODS: Between February, 2005, and August, 2007, we did a cluster-randomised trial with 16 clusters (defined as community hospitals and their catchment area). Clusters were randomly allocated by use of a variance minimisation algorithm to ParkinsonNet care (n=8) or usual care (n=8). Patients were assessed at baseline and at 8, 16, and 24 weeks of follow-up. The primary outcome was a patient preference disability score, the patient-specific index score, at 16 weeks. Health secondary outcomes were functional mobility, mobility-related quality of life, and total societal costs over 24 weeks. Analysis was by intention to treat. This trial is registered, number NCT00330694. FINDINGS: We included 699 patients. Baseline characteristics of the patients were comparable between the ParkinsonNet

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clusters (n=358) and usual-care clusters (n=341). The primary endpoint was similar for patients within the ParkinsonNet clusters (mean 47.7, SD 21.9) and control clusters (48.3, 22.4). Health secondary endpoints were also similar for patients in both study groups. Total costs over 24 weeks were lower in ParkinsonNet clusters compared with usual-care clusters (difference euro727; 95% CI 56-1399). INTERPRETATION: Implementation of ParkinsonNet networks did not change health outcomes for patients living in ParkinsonNet clusters. However, health-care costs were reduced in ParkinsonNet clusters compared with usual-care clusters. FUNDING: ZonMw; Netherlands Organisation for Scientific Research; Dutch Parkinson’s Disease Society; National Parkinson Foundation; Stichting Robuust.

PMID: 19961479 Schmeits PC, Hermans MH, van Geest-Daalderop JH, Poodt J, de Sauvage Nolting PR, Conemans JM. VKORC1 mutations in patients with partial resistance to phenprocoumon. Br J Haematol. 2010 Mar;148(6):955-7. PMID: 19962805 Penne EL, van der Weerd NC, van den Dorpel MA, Grooteman MP, Lévesque R, Nubé MJ, Bots ML, Blankestijn PJ, ter Wee PM; CONTRAST Investigators. Short-term effects of online hemodiafiltration on phosphate control: a result from the randomized controlled Convective Transport Study (CONTRAST). (Hoogeveen EK). Am J Kidney Dis. 2010 Jan;55(1):77-87. BACKGROUND: Hyperphosphatemia is an independent risk factor for all-cause and cardiovascular mortality in hemodialysis (HD) patients. Phosphate control often is unsuccessful using conventional dialysis therapies. STUDY DESIGN: Short-term analysis of a secondary outcome of an ongoing randomized controlled trial. SETTING & PARTICIPANTS: 493 (84%) consecutive patients from 589 patients included in the Convective Transport Study (CONTRAST) by January 2009 from 26 centers in 3 countries. INTERVENTION: Online hemodiafiltration (HDF) versus continuation of low-flux HD. OUTCOMES: Differences in change from baseline to 6 months in phosphate levels and proportion of patients reaching phosphate treatment targets (phosphate < or = 5.5 mg/dL). MEASUREMENTS: Phosphate, use of phosphate-binding agents, and proportion of patients achieving treatment targets at baseline, 3 months, and 6 months. RESULTS: Phosphate levels decreased from 5.18 +/- 0.10 (SE) mg/dL at baseline to 4.87 +/- 0.10 mg/dL at 6 months in HDF patients (P < 0.001) and were stable in HD patients (5.10 +/- 0.10 mg/dL at baseline and 5.03 +/- 0.10 mg/ dL after 6 months; P = 0.5). The difference in change in phosphate levels between HD and HDF patients (B = -0.24; 95% CI, -0.52 to 0.03; P = 0.08) increased after adjustment for phosphate-binder use (B = -0.36; 95% CI, -0.65 to -0.06; P = 0.02). The proportion of patients reaching phosphate treatment targets increased from 64% to 74% in HDF patients and was stable in HD patients (66% and 66%); the difference between groups reached statistical significance (P = 0.04). Nutritional parameters and residual renal function were similar in both treatment groups. LIMITATIONS: Only predialysis serum phosphate levels were measured; phosphate clearance could therefore not be calculated. CONCLUSION: HDF may help improve phosphate control. Whether this contributes to improved clinical outcome remains to be established.


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PMID: 19965537 Penne EL, van der Weerd NC, Blankestijn PJ, van den Dorpel MA, Grooteman MP, Nubé MJ, Ter Wee PM, Lévesque R, Bots ML; CONTRAST investigators.(Hoogeveen EK). Role of residual kidney function and convective volume on change in beta2-microglobulin levels in hemodiafiltration patients. Clin J Am Soc Nephrol. 2010;5:80-86. BACKGROUND AND OBJECTIVES: Removal of beta2-microglobulin (beta2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in beta2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Predialysis serum beta2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in beta2M were analyzed using multivariable linear regression models. RESULTS: Mean serum beta2M levels decreased from 29.5 +/- 0.8 (+/-SEM) at baseline to 24.3 +/- 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 +/- 0.9 to 34.4 +/- 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient -7.7 mg/L, 95% confidence interval -9.5 to -5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, beta2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The beta2M decrease was not related to convective volume. CONCLUSIONS: This study demonstrated effective lowering of beta2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on beta2M decrease appears limited, possibly because of resistance to beta2M transfer between body compartments.

PMID: 20012891 Ruiterkamp J, Voogd AC, Bosscha K, Tjan-Heijnen VC, Ernst MF. Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature. Breast Cancer Res Treat. 2010 Feb;120(1):9-16. According to current treatment standards, patients with metastatic breast cancer at diagnosis receive palliative therapy. Local treatment of the breast is only recommended if the primary tumor is symptomatic. Recent studies suggest that surgical removal of the primary tumor has a favorable impact on the prognosis of patients with primary metastatic breast cancer. We performed a systematic review of the literature to weigh the evidence for and against breast surgery in this patient group. Ten retrospective studies were found in which the use of breast surgery in primary metastatic breast cancer and its impact on survival was examined. The hazard ratios of the studies were pooled to provide an estimate of the overall effect of surgery, and the results and conclusions of the studies were analyzed. A crude analysis, without adjustment for potential confounders, showed that surgical removal of the breast lesion in stage-IV disease was associated with a significantly higher overall survival rate in seven of the ten studies, and a trend toward a better survival in the three remaining studies. Surgery of the primary tumor appeared to be an independent factor for an improved survival in the multivariate analyses from the individual studies, with hazard ratios ranging from 0.47 to 0.71. The pooled hazard ratio for overall mortality was 0.65 (95% CI 0.59-0.72) in favor of the patients undergoing surgery. This systematic review of the literature suggests that surgery of the primary breast tumor in patients with

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stage-IV disease at initial presentation does have a positive impact on survival. In order to provide a definite answer on whether local tumor control in patients with primary metastatic disease improves survival, a randomized controlled trial comparing systemic therapy with and without breast surgery is needed.

PMID: 20015414 Giard RW, Broekman JM. Missed malignant melanoma: legal considerations Ned Tijdschr Geneeskd. 2009;153:A1237. Malignant melanoma may be missed both clinically and histopathologically. The appearance of metastases after local excision of a skin lesion which was not recognized as melanoma indicates a diagnostic error. In a lawsuit three things have to be proven: that the doctor has behaved negligently, that the patient has been damaged and that there is a causal relation between the two. After local excision of a lesion that subsequently proves to be a metastasized melanoma, no damage (‘loss of chance’) occurs because neither local surgery nor adjuvant therapy influences diseasefree survival. These particularities are of importance in legal judgments.

PMID: 20016402 Ramakers BP, Pickkers P. Adenosine-mediated attenuation of the innate immune response for only those who need it? The tailored potential of pentoxifylline. Shock. 2010 Jul;34(1):105-6. PMID: 20021568 Van Nes SI, Vanhoutte EK, Faber CG, Garssen MP, van Doorn PA, Merkies IS; PeriNomS Study Group. Improving fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity scale. J Peripher Nerv Syst. 2009 Dec;14(4):268-78. Fatigue is a major disabling complaint in patients with immune-mediated neuropathies (IN). The 9-item fatigue severity scale (FSS) has been used to assess fatigue in these conditions, despite having limitations due to its classic ordinal construct. The aim was to improve fatigue assessment in IN through evaluation of the FSS using a modern clinimetric approach [Rasch unidimensional measurement model (RUMM2020)]. Included were 192 stable patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUSP). The obtained FSS data were exposed to RUMM2020 model to investigate whether this scale would meet its expectations. Also, reliability and validity studies were performed. The original FSS did not meet the Rasch model expectations, primarily based on two misfitting items, one of these also showing bias towards the factor ‘walking independent.’ After removing these two items and collapsing the original 7-point Likert options to 4-point response categories for the remaining items, we succeeded in constructing a 7-item Rasch-built scale that fulfilled all requirements of unidimensionality, linearity, and rating scale model. Good reliability and validity were also obtained for the modified FSS scale. In conclusion, a 7-item linearly weighted Rasch-built modified FSS is presented for more proper assessment of fatigue in future studies in patients with immune-mediated neuropathies.


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PMID: 20021654 Bensdorp AJ, Slappendel E, Koks C, Oosterhuis J, Hoek A, Hompes P, Broekmans F, Verhoeve H, de Bruin JP, van Weert JM, Traas M, Maas J, Beckers N, Repping S, Mol BW, van der Veen F, van Wely M. The INeS study: prevention of multiple pregnancies: a randomised controlled trial comparing IUI COH versus IVF e SET versus MNC IVF in couples with unexplained or mild male subfertility. BMC Womens Health. 2009 Dec 18;9:35. BACKGROUND: Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate.This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples. METHODS/DESIGN: We plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months. Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded.Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total). DISCUSSION: Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment.

PMID: 20032219 Schneeberger PM, Hermans MH, van Hannen EJ, Schellekens JJ, Leenders AC, Wever PC. Real-time PCR with serum samples is indispensable for early diagnosis of acute Q fever. Clin Vaccine Immunol. 2010 Feb;17(2):286-90. The world’s largest Q fever outbreak is ongoing in The Netherlands with around 3,000 confirmed cases since the first half of 2007. Increased awareness has resulted in early referral of patients for diagnostics. An important drawback to serological diagnosis of acute Q fever is the lag phase in antibody response. Therefore, we evaluated the performance of a real-time PCR for detection of Coxiella burnetii DNA using serum samples from patients with acute Q fever. PCR, targeting IS1111, was retrospectively performed on acute-phase and follow-up convalescent-phase serum samples from 65 patients with acute Q fever as diagnosed by immunofluorescence assay. The results obtained by PCR were

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related to disease stage as defined by subsequent appearance of phase II IgM, phase II IgG, phase I IgM, and phase I IgG (IgM-II, IgG-II, IgM-I, and IgG-I, respectively) antibodies and time since onset of disease. In addition, we analyzed seronegative acute-phase serum samples from patients with inconclusive Q fever serology, because no convalescentphase serum samples were available. PCR was scored positive in 49/50 (98%) seronegative sera, 9/10 (90%) sera with isolated IgM-II antibodies, 3/13 (23%) sera with IgM-II/IgG-II antibodies, 2/41 (5%) sera with IgM-II/IgG-II/IgM-I antibodies, 0/15 (0%) sera with IgM-II/IgG-II/IgM-I/IgG-I antibodies, and 0/1 (0%) serum sample with IgM-II/IgG-II/IgGI antibodies. The latest time point after onset of disease in which C. burnetii DNA could be detected was at day 17. In patients with inconclusive Q fever serology, PCR was positive in 5/50 (10%) cases. We conclude that real-time PCR with serum samples is indispensable for early diagnosis of acute Q fever. C. burnetii DNA becomes undetectable in serum as the serological response develops.

PMID: 20050490 Schuurman JP, Schoonhoven L, Defloor T, van Engelshoven I, van Ramshorst B, Buskens E. Economic evaluation of pressure ulcer care: a cost minimization analysis of preventive strategies. Nurs Econ. 2009 Nov-Dec;27(6):390-400, 415. The purpose of this study was to determine the cost for prevention and treatment of pressure ulcers from a hospital perspective and to identify the least resource-intensive pressure ulcer prevention strategy. Cost analyses were examined from a hospital perspective using direct costs. The study was carried out alongside a prospective cohort study on the incidence and risk factors for pressure ulcers. Two large teaching hospitals in the Netherlands with (partly) opposing approaches in prevention, a technological versus a human approach, were analyzed. The main outcome measures were resource use, costs of preventive measures and treatment, and pressure ulcer incidence in both hospitals. Pressure ulcer prevention through a predominantly technical approach resulted in a similar incidence rate as prevention through a predominantly human approach. However, the technical approach was considerably less expensive.

PMID: 20075649 Knol W, Keijsers CJPW, Jansen PAF, van Marum RJ. Systematic evaluation of rating scales for drug induced parkinsonism. J Clin Psychopharmacol. 2010; 30(1): 57-61. OBJECTIVE: Drug-induced parkinsonism (DIP) is one of the most common adverse effects of antipsychotic agents. The limited agreement about which rating scale should be used in clinical practice to assess DIP prompted us to review the feasibility and the psychometric qualities of the available instruments. METHODS: The PubMed and EMBASE databases were searched in November 2008 using the terms “parkinsonism,” “scale,” and “drug induced” to identify instruments used to measure DIP. Then, the literature was searched for studies investigating the use and psychometric properties of each identified instrument. Outcome measures included feasibility, validity (including appropriateness of used reference test), and reliability (internal consistency and interrater and intrarater reliability). RESULTS: Seventeen rating scales were identified, each with a different representation of the concept of parkinsonism. The Simpson Angus Scale (SAS) was used the most, followed by the Extrapyramidal Symptom Rating Scale. There were limited psychometric data, especially regarding validity, available for any scale. The SAS, the Drug-Induced Extrapyramidal Scale, and the parkinsonism subscale of the Schedule for the Assessment of Drug-Induced Movement


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Disorders, which is identical to the St Hans Rating Scale for Extrapyramidal Syndromes, seemed to have moderate to good reliability and acceptable validity. The time-consuming nature of the Schedule for the Assessment of Drug-Induced Movement Disorders would make it less useful in daily practice. CONCLUSIONS: Although various scales are used to assess DIP, few have been evaluated for validity and reliability. The SAS, St Hans Rating Scale for Extrapyramidal Syndromes, and Drug-Induced Extrapyramidal Scale seem to be the most valid, reliable, and easy-to-use instruments to evaluate DIP in clinical practice.

PMID: 20082537 Meulendijks D, Manesse CK, Jansen PAF, van Marum RJ, Egberts ACG. Antipsychotic-induced hyponatriemia: a systematic review of published evidence. Drug Safety. 2010; 33(2): 101-14. Hyponatraemia is known to occur as a rare but clinically important adverse reaction to treatment with different psychotropic drugs, including selective serotonin reuptake inhibitors and antiepileptic drugs. In past decades, reports have been published that describe the development of hyponatraemia in association with antipsychotic drug treatment. Our objective was to systematically review the available evidence on antipsychotic-induced hyponatraemia, focussing on patient characteristics, drug dosage, polydipsia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A search was carried out in the MEDLINE and EMBASE databases from January 1966 to 11 April 2009. Inclusion criteria were (i) hyponatraemia (serum sodium level <136 mmol/L) occurring after the start of treatment with an antipsychotic drug; and (ii) that the hyponatraemia potentially occurred as an adverse reaction to antipsychotic drug treatment in accordance with the WHO definition. Articles in languages other than English, Dutch, German, French and Spanish were excluded. Information on patient characteristics, medical and diagnostic data, pharmacological treatment, drug dechallenge and drug rechallenge were extracted from the publications whenever available. A causality assessment was performed on all case reports using Naranjo’s adverse drug reaction probability scale. Correlational analysis was performed to assess correlations between antipsychotic drug dosage and both serum sodium level and time to onset of hyponatraemia. We included four studies and 91 publications containing case reports and case series; no randomized controlled studies were identified. Data from the identified case reports were further analysed. The mean age of the patients was 46 years; 57% were male. The diagnosis was schizophrenia in 70% of the cases. A history of polydipsia was diagnosed as positive in 67% of the cases and negative in 23% of the cases. Polydipsia occurred in the remaining 10% of cases, although it was reported to be drug-induced (i.e. a severe increase in water intake was observed in relation to treatment with the suspected drug). Analysis of the case reports using the adverse drug reaction probability scale indicated possible causality in most cases (80%), probable causality in a significant amount of cases (19%) and unlikely causality in one case (1%). Overall correlational analysis yielded no significant correlations between defined daily dose-equivalent dosages and serum sodium or time to onset of hyponatraemia. The incidence of hyponatraemia induced by antipsychotics may be much higher than is currently thought. Both the newer atypical antipsychotics and the older drugs have been associated with the development of hyponatraemia. Physicians, psychiatrists and other healthcare workers should be aware of the possibility of hyponatraemia associated with the use of antipsychotics. Further studies are required to establish the risks of and risk factors associated with antipsychotic-induced hyponatraemia.

PMID: 20083537 Van Hulst LT, Creemers MC, Fransen J, Li LC, Grol R, Hulscher ME, van Riel PL. How to improve DAS28 use in daily clinical practice? A pilot study of a nurse-led intervention. Rheumatology (Oxford). 2010 Apr;49(4):741-8.

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OBJECTIVES: To determine whether DAS28 measurements by a specialized nurse, before the rheumatologist visit, in combination with the advice to rheumatologists to reach a DAS28 < or = 3.2, had beneficial effects on disease activity and medication prescription in patients with RA and to explore possible predictors for variation in medication changes and reasons for non-adherence to the advice to reach a DAS28 < or = 3.2. METHODS: In this pilot study, rheumatologists were randomized to ‘usual care’ (n = 3) or DAS28 measurement by a nurse prior the rheumatologist visit (n = 4). In the usual care group, the DAS28 was measured but not provided to rheumatologists. Mixed model analyses were used for analysing between-group differences and for the prediction model. Rheumatologists in the intervention group were asked to provide reasons in cases of non-adherence to the advice. RESULTS: After 18 months, DAS28 was reduced by - 0.69 and - 0.66 (P = 0.70) in, respectively, the intervention (144 patients) and the usual care (104 patients) groups. In the intervention group, medication was changed by rheumatologists in 35% of the visits with a DAS28 > 3.2; in the usual care group this was 33% (P = 0.99). Baseline DAS28 (OR 1.6; P< or =0.0001) and HAQ (OR 1.3; P = 0.03) were positively related to a medication change. The most frequently mentioned reason not to change medication was patient refusal (26%). CONCLUSIONS: DAS28 measurement by a nurse was as effective as usual care; however, this intervention without protocolized treatment adjustments is not sufficient to lead to a considerable reduction in disease activity compared with trials with protocolized treatment adjustments.

PMID: 20088343 Feitsma MT, van Laar T, Dautzenberg PL. The possible value of diagnosing MCI-DLB and treatment options. Tijdschr Gerontol Geriatr. 2009 Sep;40(4):168-72. Dementia with Lewy Bodies (DLB) is a well-described clinical entity. DLB patients can be treated with acetylcholinesterase inhibitors (AChEI’s). However, should we also treat patients who have but part of the symptoms and who are currently described as MCI-DLB? Will these MCI-DLB patients benefit from AChEI’s in terms of direct effect on cognition and behaviour and final outcome? Two cases are presented to demonstrate the clinical features of MCI-DLB and the effect of treatment with rivastigmine (AChEI). The discussion then focuses on the possible value of diagnosing MCI-DLB and if this diagnosis should result in a different medication treatment than the diagnosis MCI-AD, for which AChEI medication is not recommended.

PMID: 20089560 Herbers AHE, Feuth T, Donnelly JP, Blijlevens NM. Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy. Ann Oncol.2010 Aug;21(8):1706-11. BACKGROUND: Currently, objective tests are lacking that enable the extent and duration of intestinal mucosal damage induced by myeloablative chemotherapy to be determined. To address this problem, we explored a citrulline-based assessment score as this amino acid is a simple quantitative marker of intestinal failure. PATIENTS AND METHODS: From March 2004 to June 2007, citrulline concentrations were determined at baseline and at least once weekly after the start of myeloablative chemotherapy until 30 days thereafter among 94 allogeneic or autologous haematopoietic stem-cell transplant recipients. The patients were divided into three groups according to the regimen they received: (i) carmustine, etoposide, cytarabine and melphalan/high-dose melphalan, (ii) cyclophosphamide and total body irradiation +/- antithymocyte globulin and (iii) idarubicin-containing regimens. Intestinal


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mucosal damage was described either by level of citrulline on each day, on the basis of different thresholds of citrulline indicating the severity of villous atrophy, or by area under the curve using reciprocal value of 10/citrulline. RESULTS: Regimens that incorporated idarubicin induced the most severe intestinal toxicity. Scores based on the level of citrulline, using severity thresholds, and on the area under the reciprocal curve are able to discriminate between the damage induced by different high-dose chemotherapy regimens. CONCLUSION: A citrulline-based assessment score appears objective, validated, reproducible, reliable, specific and sensitive making it a suitable first choice for measuring and monitoring intestinal mucositis.

PMID: 20098344 Verstegen RH, Kusters MA, Gemen EF, de Vries E. Down syndrome B-lymphocyte subpopulations, intrinsic defect or decreased T-lymphocyte help. Pediatr Res. 2010 May;67(5):563-9. Down syndrome (DS) is known for increased incidence of respiratory infections and autoimmune diseases, indicating impaired immunity. Until now, attention has been mainly focused on T lymphocytes. Therefore, we determined Blymphocyte subpopulations in 95 children with DS compared with 33 age-matched control (AMC) children. DS serum immunoglobulin levels were compared with 962 non-DS children with recurrent infections. The results were combined with clinical data. Transitional and naive B lymphocytes are profoundly decreased in the children with DS. This could be caused by an intrinsic B-lymphocyte defect resulting in (partial) failure of B-lymphocyte generation, decreased antigen-induced proliferation and/or increased apoptosis, or by decreased proliferation due to deficient T-lymphocyte help, or a combination of these. The decreased CD27, CD21, and CD23 cells are reminiscent of common variable immunodeficiency and suggestive of disturbed peripheral B-lymphocyte maturation. Immunoglobulin levels in DS are abnormal-as has been described before-and different from non-DS children with recurrent infections. We conclude that the humoral immune system is abnormal in DS, but could not find a relation between B-lymphocyte subsets, immunoglobulins and clinical features of the children with DS in our cohort, nor could we answer the question whether DS lymphocytes are truly intrinsically deficient, or could all findings be explained by deficient T-lymphocyte help.

PMID: 20098345 Kusters MA, Gemen EF, Verstegen RH, Wever PC, de Vries E. Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T lymphocytes. Pediatr Res. 2010 May;67(5):557-62. Because of their increased malignancies, autoimmune diseases, and infections, patients with Down syndrome (DS) show features of immunodeficiency. The DS thymus and T lymphocyte subsets have indeed proven to be different, and this has been interpreted as precocious aging. Our study on T lymphocyte subpopulations in DS shows that the normal expansion of naive helper (CD4CD45RA) and cytotoxic (CD8CD45RACD27) T lymphocytes is lacking in the first years of life; this is more logically explainable with an intrinsic T lymphocyte defect. Furthermore, memory cell numbers are not different from age-matched controls (AMC), which does not support the hypothesis of precocious aging. Although the absolute numbers of T lymphocyte subpopulations approach AMC levels toward adulthood, the persistent clinical problems suggest that these cells may not function optimally. However, the clinical picture does not fit severe T lymphocyte deficiency. The latter concept is also supported by our finding that cytomegalovirus (CMV)-seropositive DS children show similar numbers of terminally differentiated cytotoxic T lymphocytes when compared with healthy children, not increased numbers as are seen in immunocompromised hosts.

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PMID: 20102956 Van Beek E, Binkhorst M, de Hoog M, de Groot P, van Dijk A, Schokking M, Hopman M. Exercise performance and activity level in children with transposition of the great arteries treated by the arterial switch operation. Am J Cardiol 2010; 105: 398-403. The exercise capacity of children after arterial switch for transposition of the great arteries (TGA) is known to be at the lower limit of normal. We aimed to ascertain whether this results from compromised hemodynamics or deconditioning. A total of 17 children with TGA (12 male and 5 female children; age 12.1 + or - 2.0 years) treated with the arterial switch operation were compared with 20 age-matched controls (13 male and 7 female children; age 12.8 + or - 2.4 years) regarding their peak exercise capacity, peak workload, and peak heart rate, as assessed by cycle ergometry. The children’s physical activity level was monitored for a 7-day period using a pedometer and diary, and a questionnaire was used to assess physical activity participation and overprotection. The results demonstrated that TGA children showed a significantly reduced peak exercise capacity (47.4 + or - 6.4 vs 41.1 + or - 6.6 ml/kg/min; p <0.05), maximal workload (3.7 + or - 0.5 vs 3.1 + or - 0.6 W/kg; p <0.01), and maximal heart rate (189 + or - 9 vs 180 + or - 14 beats/min; p <0.05) compared to the controls. No significant differences were found in the physical activity pattern or overprotection. In conclusion, given the comparable physical activity level, but reduced exercise capacity in the TGA children, these children most likely fall short in their exercise performance because of restrictive hemodynamics rather than deconditioning from reduced daily life activity.

PMID: 20105278 Scheffer RC, Bredenoord AJ, Hebbard GS, Smout AJ, Samsom M. Effect of proximal gastric volume on hiatal hernia. Neurogastroenterol Motil. 2010 May;22(5):552-6, e120. BACKGROUND: Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro-esophageal reflux. This can be studied with high-resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. METHODS: Twenty gastro-esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High-resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three-dimensional ultrasonography before and every 15 min after meal ingestion. KEY RESULTS: During fasting, the hernia profile [2 separate high-pressure zones (HPZs) at manometry] was present for 31.9 +/- 4.9 min h(-1) (53.2%) in GERD patients, and 8.7 +/- 3.3 min h(-1) (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 +/- 4.2 min h(-1), 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 +/- 1.1 per hour in GERD patients and 2.5 +/- 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 +/- 1.1 per hour and 18.4 +/- 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 +/- 0.6 per hour; P < 0.05 and 3.8 +/- 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = -0.45; P < 0.05) in GERD patients, but not in controls.


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CONCLUSIONS & INFERENCES: (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra-thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.

PMID: 20121439 Rutten GJ, Ramsey NF. The role of functional magnetic resonance imaging in brain surgery. Neurosurg Focus 2010 Feb;28(2): E4. New functional neuroimaging techniques are changing our understanding of the human brain, and there is now convincing evidence to move away from the classic and clinical static concepts of functional topography. In a modern neurocognitive view, functions are thought to be represented in dynamic large-scale networks. The authors review the current (limited) role of functional MR imaging in brain surgery and the possibilities of new functional MR imaging techniques for research and neurosurgical practice. A critique of current clinical gold standard techniques (electrocortical stimulation and the Wada test) is given.

PMID: 20121528 De Reu PA, Oosterbaan HP, Smits LJ, Nijhuis JG. Avoidable mortality in small-for-gestational-age children in the Netherlands. An analysis of 59 successive cases of perinatal death in singletons with birth weights below the 10th centile. J Perinat Med. 2010 May;38(3):311-8. OBJECTIVE: To analyze avoidable perinatal mortality in small-for-gestational-age (SGA) children. METHODS: All SGA-children (< or =10(th) percentile) among 22,189 newborns delivered after 24 weeks’ gestation (175 days), from three regions of the Netherlands during 2003-2004 were evaluated. Cases of perinatal mortality were identified and assessed in a consensus model by perinatal audit groups for cause of death and the presence of substandard care factors (SSF). We analyzed all singleton SGA-cases with and without SSF for avoidable perinatal mortality. RESULTS: Out of 20,927 singletons, 2396 newborns were SGA. Of those, 59 died perinatally (2.46%), and 55 of which were assessed by perinatal audit groups. SSF by caregivers were found in 22 cases (40%). In 16 of these cases (29%) the relation to the perinatal death was considered possible or (very) probable. Of the cases without SSF by caregivers, 15 cases (25%) could possibly have been avoided: in 13 cases an avoidable condition and in 2 cases avoidable death were identified. Failure in the correct and timely diagnosis of fetal growth restriction appears to be an important issue in all cases of perinatal mortality in SGA-children. Before referral growth restriction was suspected only in 22% of all SGA cases during the third trimester of pregnancy. CONCLUSIONS: More adequate action by caregivers could decrease perinatal mortality in nearly 1/3 among SGAchildren. Adjustments in pregnancy monitoring, especially in low-risk pregnancies, such as routine ultrasound biometry examination, may improve the accuracy in detecting growth deviations and decreasing the number of possibly avoidable cases of perinatal mortality in this category.

PMID: 20149482 Jager MM, Murk JL, Pique R, Wulf MW, Leenders AC, Buiting AG, Bogaards JA, Kluytmans JA, Vandenbroucke-Grauls CM. Prevalence of carriage of meticillin-susceptible and meticillin-resistant Staphylococcus aureus in

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employees of five microbiology laboratories in The Netherlands. J Hosp Infect 2010 Mar;74(3):292-4. PMID: 20176027 Hartley JL, Zachos NC, Dawood B, Donowitz M, Forman J, Pollitt RJ, Morgan NV, Tee L, Gissen P, Kahr WHA, Knisely AS, Watson S, Chitayat D, Booth IW, Protheroe S, Murphy S, de Vries E, Kelly DA, Maher ER. Mutations in TTC37 Cause Trichohepatoenteric Syndrome (Phenotypic Diarrhoea of Infancy). Gastroenterology. 2010 Jun;138(7):2388-98, 2398.e1-2. BACKGROUND & AIMS: Trichohepatoenteric syndrome (THES) is an autosomal-recessive disorder characterized by life-threatening diarrhea in infancy, immunodeficiency, liver disease, trichorrhexis nodosa, facial dysmorphism, hypopigmentation, and cardiac defects. We attempted to characterize the phenotype and elucidate the molecular basis of THES. METHODS: Twelve patients with classic THES from 11 families had detailed phenotyping. Autozygosity mapping was undertaken in 8 patients from consanguineous families using 250,000 single nucleotide polymorphism arrays and linked regions evaluated using microsatellite markers. Linkage was confirmed to one region from which candidate genes were analyzed. The effect of mutations on protein production and/or localization in hepatocytes and intestinal epithelial cells from affected patients was characterized by immunohistochemistry. RESULTS: Previously unrecognized platelet abnormalities (reduced platelet alpha-granules, unusual stimulated alpha granule content release, abnormal lipid inclusions, abnormal platelet canalicular system, and reduced number of microtubules) were identified. The THES locus was mapped to 5q14.3-5q21.2. Sequencing of candidate genes showed mutations in TTC37, which encodes the uncharacterized tetratricopeptide repeat protein, thespin. Bioinformatic analysis suggested thespin to be involved in protein-protein interactions or chaperone. Preliminary studies of enterocyte brush-border ion transporter proteins (sodium hydrogen exchanger 2, sodium hydrogen exchanger 3, aquaporin 7, sodium iodide symporter, and hydrogen potassium adenosine triphosphatase [ATPase]) showed reduced expression or mislocalization in all THES patients with different profiles for each. In contrast the basolateral localization of Na/K ATPase was not altered. CONCLUSIONS: THES is caused by mutations in TTC37. TTC37 mutations have a multisystem effect, which may be owing to abnormal stability and/or intracellular localization of TTC37 target proteins.

PMID: 20186761 Koebrugge B, Bosscha K, Jager G, Ernst M. Accuracy of transrectal ultrasonography in staging rectal tumors that are clinically eligible for transanal endoscopic microsurgery. J Clin Ultrasound. 2010 Jun;38(5):250-3. PURPOSE: Transanal endoscopic microsurgery (TEM) is performed in patients with premalignant or selected stage T1 rectal lesions. Transrectal ultrasonography (TRUS) is an important tool in the preoperative staging of rectal lesions to determine whether lesions are suitable for TEM or not. We analyze the accuracy of TRUS in distinguishing between rectal lesions requiring TEM or more radical excision. METHODS: From 2006 to 2008 thirty-five patients were included. All patients underwent TRUS. Following TRUS and/or additional imaging, patients underwent surgery. Preoperative TRUS staging was correlated to postoperative pathology findings. RESULTS: In 30 patients TRUS was diagnostic. Postoperative pathologic findings confirmed the preoperative TRUS findings in 29 patients; in 1 patient, a T3 staged tumor was an overstaged lesion biopsied as a tubulovillous adenoma.


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The accuracy level in the diagnostic TRUS group was 97% (29/30). In 5 patients TRUS was nondiagnostic; in 4 of these patients MRI was performed showing no tumor invasion in all 4 patients, confirmed by pathologic findings. Correct TRUS interpretation was possible in 86% (30/35). Overall accuracy of TRUS was 83% (29/35). CONCLUSION: TRUS is accurate in distinguishing rectal lesions suitable for TEM from the lesions needing more radical surgery. If TRUS is nondiagnostic or the lesion is of high stage (>or=T2), MRI should be performed.

PMID: 20201011 Deniz G, Chapel H, Barlan I, de Vries E, Jaraquemada D. Women advancing science. Eur J Immunol. 2010 Mar;40(3):589-92. PMID: 20219351 Dassen AE, Lemmens VE, van de Poll-Franse LV, Creemers GJ, Brenninkmeijer SJ, Lips DJ, Vd Wurff AA, Bosscha K, Coebergh JW. Trends in incidence, treatment and survival of gastric adenocarcinoma between 1990 and 2007: a population-based study in the Netherlands. Eur J Cancer. 2010 Apr;46(6):1101-10. BACKGROUND: Survival of gastric cancer in the Western world remains poor. We conducted a retrospective populationbased study to evaluate trends in incidence, treatment and outcome of gastric adenocarcinoma. METHODS: All patients diagnosed with gastric adenocarcinoma during 1990-2007 in the Dutch Eindhoven Cancer Registry area were included (n=4,797). Trend analyses were conducted for incidence, mortality, tumour and patient characteristics, treatment and crude overall survival, according to tumour location (cardia versus non-cardia). Temporal changes in the odds of undergoing surgery and the risk of death were analysed by means of multivariable regression methods. RESULTS: Age-standardised incidence decreased among males (24-12 per 100,000 inhabitants) and females (10-6); mortality rates decreased at a similar pace. The proportion of cardia tumours remained stable. Stage distribution worsened over time among patients with cardia (stages I and II: 32% in 1990-1993 and 22% in 2006-2007, p=0.005) and non-cardia (stage IV: 33% in 1990-1993 and 40% in 2006-2007, p=0.0003) cancer. Chemotherapy rates increased in all settings. Five-year survival worsened over time for patients with non-cardia tumours. Age and stage had significant influence on survival after stratification for tumour localisation. After adjustments for relevant factors (i.e. stage), the risk of death decreased since the late 90s for patients with a cardia tumour (hazard ratio 0.8, p=0.01). CONCLUSION: The absence of improvement in survival rates indicates the need for earlier detection and prospective studies to evaluate new therapy regimens with standardised surgery and pathology.

PMID: 20224425 Draisma A, Dorresteijn MJ, Bouw MP, van der Hoeven JG, Pickkers P. The role of cytokines and inducible nitric oxide synthase in endotoxemia-induced endothelial dysfunction. J Cardiovasc Pharmacol. 2010 Jun;55(6):595-600. Sepsis is characterized by a blunted vascular responses due to impairment of endothelial function. The aim of our study was to assess endothelial function and the role of cytokines and nitric oxide (NO). Endotoxin tolerance was induced in 14 healthy volunteers by intravenous injection of 2 ng.kg.d lipopolysaccharide on 5 consecutive days. Forearm blood flow (FBF) was measured by strain-gauge plethysmography during dose-response curves of endothelium-dependent vasodilator acetylcholine and endothelium-independent vasodilator sodium nitroprusside

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before and 4 hours after LPS administration on days 1 and 5. In another study, 7 healthy volunteers were given selective inducible NO synthase inhibitor aminoguanidine intravenous continuously from 1 hour after a single LPS administration until 5 hours. FBF showed an attenuation of ACh-induced vasodilatory response with 67% (45%-72%) 4 hours after the first LPS administration (P = 0.01) with an unchanged dose-response curve to sodium nitroprusside. This attenuation to ACh infusion did not occur in the presence of aminoguanidine (P = 0.21) and also did not occur when tolerance was present on day 5 (P = 0.45). Our data demonstrate that endothelial dysfunction caused by endotoxemia does not occur when endotoxin tolerance develops, indicated by the absence of cytokine production and during administration of selective inducible NO synthase inhibitor aminoguanidine in vivo.

PMID: 20230650 Schimmer B, ter Schegget R, Wegdam M, Züchner L, de Bruin A, Schneeberger PM, Veenstra T, Vellema P, van der Hoek W. The use of a geographic information system to identify a dairy goat farm as the most likely source of an urban Q-fever outbreak. BMC Infect Dis 2010 Mar 16; 10: 69. BACKGROUND: A Q-fever outbreak occurred in an urban area in the south of the Netherlands in May 2008. The distribution and timing of cases suggested a common source. We studied the spatial relationship between the residence locations of human cases and nearby small ruminant farms, of which one dairy goat farm had experienced abortions due to Q-fever since mid April 2008. A generic geographic information system (GIS) was used to develop a method for source detection in the still evolving major epidemic of Q-fever in the Netherlands. METHODS: All notified Q-fever cases in the area were interviewed. Postal codes of cases and of small ruminant farms (size >40 animals) located within 5 kilometres of the cluster area were geo-referenced as point locations in a GISmodel. For each farm, attack rates and relative risks were calculated for 5 concentric zones adding 1 kilometre at a time, using the 5-10 kilometres zone as reference. These data were linked to the results of veterinary investigations. RESULTS: Persons living within 2 kilometres of an affected dairy goat farm (>400 animals) had a much higher risk for Q-fever than those living more than 5 kilometres away (Relative risk 31.1 [95% CI 16.4-59.1]). CONCLUSIONS: The study supported the hypothesis that a single dairy goat farm was the source of the human outbreak. GIS-based attack rate analysis is a promising tool for source detection in outbreaks of human Q-fever.

PMID: 20298633 Koebrugge B, Hermens RA. A women with a lumpy calf. Ned Tijdschr Geneeskd. 2010;154:A440. A 24-year-old woman had big neurofibromas on her left leg caused by type 1 neurofibromatosis. Four kilograms of tissue were excised.

PMID: 20299957 Van Luin M, Van der Ende ME, Richter C, Visser M, Faraj D, Van der Ven A, Gelinck L, Kroon F, Wit FW, Van Schaik RH, Kuks PF, Burger DM. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ ritonavir. AIDS. 2010 May 15;24(8):1223-6.


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HIV-infected travellers frequently use atovaquone/proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)0-->t for atovaquone relative to the healthy volunteers was 0.25 (0.16-0.38), 0.26 (0.17-0.41) and 0.54 (0.35-0.83) for patients on efavirenz, lopinavir/ritonavir and atazanavir/ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38-43%). Physicians should be alert for atovaquone/proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir.

PMID: 20350500 Van der Hoek W, Dijkstra F, Schimmer B, Schneeberger PM, Vellema P, Wijkmans C, ter Schegget R, Hackert V, van Duynhoven Y. Q fever in the Netherlands: an update on the epidemiology and control measures. Euro Surveill 2010 Mar 25;15(12):pii=19520. Since the steady rise in human cases which started in 2007, Q fever has become a major public health problem in the Netherlands with 2,357 human cases notified in the year 2009. Ongoing research confirms that abortion waves on dairy goat farms are the primary source of infection for humans, primarily affecting people living close (under 5 km) to such a dairy goat farm. To reverse the trend of the last three years, drastic measures have been implemented, including the large-scale culling of pregnant goats on infected farms.

PMID: 20351334 Krzakowski M, Ramlau R, Jassem J, Szczesna A, Zatloukal P, Von Pawel J, Sun X, Bennouna J, Santoro A, Biesma B, Delgado FM, Salhi Y, Vaissiere N, Hansen O, Tan EH, Quoix E, Garrido P, Douillard JY. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol. 2010 May 1;28(13):2167-73. PURPOSE: To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Randomized, multicenter, phase III study, 551 patients received either vinflunine 320 mg/m(2) or docetaxel 75 mg/m(2) every 21 days until disease progression or serious toxicity. The primary end point was progression-free survival (PFS). The noninferiority analysis was based on a 10% difference (types I/II error rates: 5%/20%). Secondary end points included response rate (ORR), response duration, overall survival (OS), clinical benefit, quality of life (QOL), and safety. RESULTS: Median PFS was 2.3 months for each arm (HR, 1.004; 95% CI, 0.841 to 1.199). ORR, stable disease, median OS, were 4.4% versus 5.5%, 36.0% versus 39.6%, 6.7 versus 7.2 months (HR, 0.973; 95% CI, 0.805 to 1.176), respectively. No significant difference in patient benefit and QOL (Functional Assessment of Cancer Therapy-Lung). No unexpected adverse events were observed. Grade higher than 0 (vinflunine v docetaxel) anemia (82.1% v 79.8%), neutropenia (49.3 v 39.02%), thrombocytopenia (30.6% v 14.3%), febrile neutropenia (3.3% v 4.7%), constipation (39.2% v 11.7%), fatigue (36.6% v 33.9%), injection site reaction (31.9% v 0.7%), nausea (26.7% v 23.7%), vomiting (23.8% v 14.2%), alopecia (19.8% v 35.4%), stomatis (19.4% v 12.4%), abdominal pain (20.1% v 3.6%), myalgia (14.7% v 6.6%), peripheral neuropathy (10.7% v 15.0%), arthralgia (7.0% v 7.7%), diarrhea (6.2% v 12.4%), edema (1.5% v 5.4%), and nail disorders (1.1% v 5;1%) were observed. CONCLUSION: This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel.

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Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC.

PMID: 20356426 Spee J, van Marum RJ, Egberts ACG, Drenth van Maanen AC, Jansen PAF. The process of bringing medication in line: the additional benefits of a Structured Medication History. [Het Medicatie Afstemmingsproces op een afdeling geriatrie: de aanvullende waarde van een Gestructureerde Medicatie Anamnese.] Ned Tijdsch v Geneesk. 2010; 154: A904. OBJECTIVE: To determine the additional benefits of a structured history-taking of medication use (SHIM) from patients admitted to a geriatric ward for obtaining a complete and accurate list of medication used at home, in comparison to an unstructured medication history-taking by the resident physician. DESIGN: Prospective, observational. METHOD: The SHIM, a standardized questionnaire, was used for history-taking from patients admitted to the geriatric ward, and often from their caregivers, too. The number and type of discrepancies were noted between this medication history and the medication history obtained by the resident physician at admission as noted on the medical chart. Discrepancies were assessed for clinical relevance. RESULTS: The SHIM was used for 47 patients with a mean age of 84.4 years. At least one discrepancy was found in all patients. Comparison of the SHIM to the medication history obtained by the resident physician revealed 4.2 discrepancies per patient on average. Omission of medication in the history taken by the resident was the most common discrepancy. 66% of all discrepancies were considered as potentially clinically relevant; in 19% of the patients this actually resulted in a moderate degree of discomfort or clinical deterioration. The number of discrepancies was statistically significantly associated with the use of a higher number of medications and with the use of ‘over the counter’ (OTC) medications. CONCLUSION: The SHIM provides a better insight into the actual use of medication by the patient than history taking of medication use by the resident at admission.

PMID: 20378563 Labar B, Suciu S, Willemze R, Muus P, Marie JP, Fillet G, Berneman Z, Jaksic B, Feremans W, Bron D, Sinnige H, Mistrik M, Vreugdenhil G, de Bock R, Nemet D, Gilotay C, Amadori S, De Witte T; on behalf of the EORTC Leukemia Group. Dexamethasone versus prednisolone for adult acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma LBL) patients - final results of the ALL-4 randomized, Phase III trial of the EORTC Leukemia Group. Haematologica 2010; 95(9):1489-95. BACKGROUND: Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. DESIGN AND METHODS: Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1-8 and 15-22, either dexamethasone 8 mg/m(2) or prednisolone 60 mg/m(2). Those who reached complete remission were given two courses of consolidation therapy


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with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was eventfree survival and the analyses was conducted on an intention-to-treat basis. RESULTS: Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (+/-SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75-1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76-1.40). The 6-year cumulative incidences of relapse were 49.8% and 53.5% (Gray’s test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray’s test: P=0.07). CONCLUSIONS: In the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone.

PMID: 20384753 Erceg A, Greebe RJ, Bovenschen HJ, Seyger MM. A Comparative Study of Pulsed 532-nm Potassium Titanyl Phosphate Laser and Electrocoagulation in the Treatment of Spider Nevi. Dermatologic surgery 2010;36:630-635. OBJECTIVE: To assess the clinical efficacy and safety of potassium titanyl phosphate (KTP) laser treatment and electrocoagulation (EC) for the treatment of spider nevi (SN). METHOD: A randomized single-blind intrapatient comparison study was performed. A blinded observer and patients reported the clinical treatment outcome and pain on a visual analogue scale (0-10). Side effects were noted if present. RESULTS: Mean physician-rated clinical efficacy scores+/-standard error of the mean were 7.7+/-0.7 for KTP laser and 6.2+/-0.9 for EC treatment (p=.05). Patient-rated mean clinical efficacy of KTP laser was 8.3+/-0.6 and of EC was 7.3+/-0.7 (p=.09). Stratification for potential confounding bias, such as location of SN, central bulging vein, and diameter (p=.25) of the treated SN did not reveal any statistically significant differences between the treatments. Treatment with KTP or EC did not result in scarring or pigmentary changes. Pain was reported for KTP treatment (3.1+/-0.4) and EC (6.4+/-0.7) (p<.05). CONCLUSION: Clinical efficacy of KTP laser and EC for SN is comparable, although there is a tendency toward an advantage in favor of the KTP laser. KTP laser treatment was less painful.

PMID: 20398172 Sleegers MJ, Beutler JJ, Hardon WJ, Berden JH, Verhave JC, Conemans JM, Hollander DA, Dautzenberg PL, Hoogeveen EK. Reversible rapidly progressive dementia with parkinsonism induced by valproate in a patient with systemic lupus erythematosus. J Am Geriatr Soc. 2010 Apr;58(4):799-801.

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PMID: 20400675 Pillay J, Ramakers BP, Kamp VM, Loi AL, Lam SW, Hietbrink F, Leenen LP, Tool AT, Pickkers P, Koenderman L. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010 Jul;88(1):211-20. Neutrophils play an important role in host defense. However, deregulation of neutrophils contributes to tissue damage in severe systemic inflammation. In contrast to complications mediated by an overactive neutrophil compartment, severe systemic inflammation is a risk factor for development of immune suppression and as a result, infectious complications. The role of neutrophils in this clinical paradox is poorly understood, and in this study, we tested whether this paradox could be explained by distinct neutrophil subsets and their functionality. We studied the circulating neutrophil compartment immediately after induction of systemic inflammation by administering 2 ng/kg Escherichia coli LPS i.v. to healthy volunteers. Neutrophils were phenotyped by expression of membrane receptors visualized by flow cytometry, capacity to interact with fluorescently labeled microbes, and activation of the NADPH-oxidase by oxidation of Amplex Red and dihydrorhodamine. After induction of systemic inflammation, expression of membrane receptors on neutrophils, such as CXCR1 and -2 (IL8Rs), C5aR, FcgammaRII, and TLR4, was decreased. Neutrophils were also refractory to fMLF-induced up-regulation of membrane receptors, and suppression of antimicrobial function was shown by decreased interaction with Staphylococcus epidermis. Simultaneously, activation of circulating neutrophils was demonstrated by a threefold increase in release of ROS. The paradoxical phenotype can be explained by the selective priming of the respiratory burst. In contrast, newly released, CD16(dim) banded neutrophils display decreased antimicrobial function. We conclude that systemic inflammation leads to a functionally heterogeneous neutrophil compartment, in which newly released refractory neutrophils can cause susceptibility to infections, and activated, differentiated neutrophils can mediate tissue damage.

PMID: 20403089 Van Geest-Daalderop JH, Kraaijenhagen RJ, Van Der Meer FJ, Van Den Besselaar AM. Intraindividual variation of the International Normalized Ratio in patients monitored with a recombinant human thromboplastin. J Thromb Haemost. 2010 Jul;8(7):1641-2. PMID: 20410514 Van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG; Dutch Pancreatitis Study Group. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010 Apr 22;362(16):1491-502. BACKGROUND: Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. METHODS: In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The


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step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. RESULTS: The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P=0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P=0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P=0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P=0.03) and new-onset diabetes (16% vs. 38%, P=0.02). CONCLUSIONS: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue.

PMID: 20422184 Hoetjes NJ, van Velden FH, Hoekstra OS, Hoekstra CJ, Krak NC, Lammertsma AA, Boellaard R. Partial volume correction strategies for quantitative FDG PET in oncology. Eur J Nucl Med Mol Imaging. 2010 Aug;37(9):1679-87. PURPOSE: Quantitative accuracy of positron emission tomography (PET) is affected by partial volume effects resulting in increased underestimation of the standardized uptake value (SUV) with decreasing tumour volume. The purpose of the present study was to assess accuracy and precision of different partial volume correction (PVC) methods. METHODS: Three methods for PVC were evaluated: (1) inclusion of the point spread function (PSF) within the reconstruction, (2) iterative deconvolution of PET images and (3) calculation of spill-in and spill-out factors based on tumour masks. Simulations were based on a mathematical phantom with tumours of different sizes and shapes. Phantom experiments were performed in 2-D mode using the National Electrical Manufacturers Association (NEMA) NU2 image quality phantom containing six differently sized spheres. Clinical studies (2-D mode) included a testretest study consisting of 10 patients with stage IIIB and IV non-small cell lung cancer and a response monitoring study consisting of 15 female breast cancer patients. In all studies tumour or sphere volumes of interest (VOI) were generated using VOI based on adaptive relative thresholds. RESULTS: Simulations and experiments provided similar results. All methods were able to accurately recover true SUV within 10% for spheres equal to and larger than 1 ml. Reconstruction-based recovery, however, provided up to twofold better precision than image-based methods. Clinical studies showed that PVC increased SUV by 5-80% depending on tumour size. Test-retest variability slightly worsened from 9.8 +/- 6.5 without to 10.8 +/- 7.9% with PVC. Finally, PVC resulted in slightly smaller SUV responses, i.e. from -30.5% without to -26.3% with PVC after the first cycle of treatment (p < 0.01). CONCLUSION: PVC improves accuracy of SUV without decreasing (clinical) test-retest variability significantly and it has a small, but significant effect on observed tumour responses. Reconstruction-based PVC outperforms image-based methods, but requires dedicated reconstruction software. Image-based methods are good alternatives because of their ease of implementation and their similar performance in clinical studies.

PMID: 20428415 Esselink AC, de Ruijter AM, Daniëls MC. Application of NHG guidelines in patients referred for stable chest pain syndromes. Neth Heart J. 2010 Apr;18(4):178-82.

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Purpose. Guidelines of the Dutch Association of General Practitioners (NHG) dictate the evaluation, treatment, and referral process of patients with stable chest pain syndromes (CPS). Adherence to this guideline was assessed in a consecutive group of patients referred to our hospital. Methods. We retrospectively studied the records of 296 subjects referred to our outpatient department in 2007 for evaluation of stable CPS. Referral letters were checked for completeness (past and present history, mentioning of risk factors for cardiovascular disease, physical examination, listing of medication) and used to judge adherence to the guideline. In a subset of patients, additional information regarding the referral process was gathered by telephone interview. Results. The referral letter was complete in only 67 patients (23%); items most often not reported were physical examination (63%) and cardiovascular risk factors (62%). Judging from the referral letter, 23 patients (8%) were evaluated in accordance with the NHG guideline prior to their referral. In patients in whom the final diagnosis of angina pectoris was made by the cardiologist, this was 20%. Seventy-nine patients were contacted by telephone after their work-up by the cardiologist; 36 of them (44%) reported being referred at their first visit to their primary physician, while 14 (18%) were referred at their own request. Conclusion: Prior to referral, only a minority of patients with stable CPS were evaluated and treated in accordance with NHG guidelines. Furthermore, their referral letter was often incomplete.

PMID: 20444270 Van den Boogaard M, Ramakers BP, van Alfen N, van der Werf SP, Fick WF, Hoedemaekers CW, Verbeek MM, Schoonhoven L, van der Hoeven JG, Pickkers P. Endotoxemia-induced inflammation and the effect on the human brain. Crit Care. 2010;14(3):R81. INTRODUCTION: Effects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described. METHODS: Experimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-alpha, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined. RESULTS: Following LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-beta changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found. CONCLUSIONS: Short-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness.

PMID: 20445470 Delawi D, Dhert WJ, Rillardon L, Gay E, Prestamburgo D, Garcia-Fernandez C, Guerado E, Specchia N, Van Susante JL, Verschoor N, Quarles van Ufford HM, Oner FC. A Prospective, Randomized, Controlled, Multicenter Study of Osteogenic Protein-1 in Instrumented Posterolateral Fusions. Report on Safety and Feasibility. SPINE (Phila Pa 1976). 2010 May 20;35(12):1185-91.


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STUDY DESIGN: A prospective, randomized, controlled, multicenter clinical study. OBJECTIVE: To evaluate the safety and feasibility of osteogenic protein (OP)-1 in 1-level lumbar spine instrumented posterolateral fusions. SUMMARY OF BACKGROUND DATA: Instrumented posterolateral fusion with the use of autograft is a commonly performed procedure for a variety of spinal disorders. However, harvesting of bone from the iliac crest is associated with complications. A promising alternative for autograft are bone morphogenetic proteins. METHODS: As part of a larger prospective, randomized, multicenter study, 36 patients were included, who received a 1-level instrumented posterolateral fusion of the lumbar spine. All patients had a degenerative or isthmic spondylolisthesis with symptoms of neurologic compression. There were 2 treatment arms: OP-1 combined with locally available bone from laminectomy (OP-1 group) or iliac crest autograft (autograft group). The primary outcome was the fusion rate based on a computed tomography scan after 1-year follow-up. The clinical outcome was measured using the Oswestry Disability Index. Additionally, the safety of OP-1 was evaluated by comparing the number and severity of adverse events that occurred between both groups. RESULTS: Using strict criteria, fusion rates of 63% were found in the OP-1 group and 67% in the control group (P = 0.95). There was a decrease in Oswestry scores at subsequent postoperative time points compared with preoperative values (P > 0.001). There were no significant differences in the mean Oswestry scores between the study group and control group at any time point (P = 0.56). No product-related adverse events occurred. CONCLUSION: The results demonstrate that OP-1 combined with locally obtained autograft is a safe and effective alternative for iliac crest autograft in instrumented single-level posterolateral fusions of the lumbar spine. The main advantage of OP-1 is that it avoids morbidity associated with the harvesting of autogenous bone grafts from the iliac crest.

PMID: 20448058 Van Wijk PT, Boland GJ, Voss A, Schneeberger PM. Impact of new guidelines for blood exposure incidents in The Netherlands. Occup Med (Lond). 2010 Jun;60(4):270-6. BACKGROUND: In 2007, a new set of guidelines for blood exposure incidents was introduced in The Netherlands to standardize management and reduce use of hepatitis B immunoglobulin (HBIg). Accidents now have to be assigned into risk categories with the corresponding medical intervention. AIMS: To study the consequences of the guidelines on overall risk assessment and costs of hepatitis B virus (HBV) prevention. METHODS: Incidents (n = 461) from both hospital as well as non-hospital health care workers and others registered by a call centre from the year 2005 were reassessed and reclassified as ‘no-risk’, ‘high-risk’ or ‘low-risk’ according to the corresponding risk categories of the new guidelines. The differences in classification, use of HBV immunoglobulin, source testing and the costs of the HBV prevention strategy were evaluated. RESULTS: Of all incidents, 86% could be reassigned directly into the new risk categories. However, there was a significant shift from ‘low-’ to ‘high-risk’ incidents. Overall, administration of HBV vaccination increased and administration of HBIg decreased significantly, although within the group of high-risk incidents, administration of HBIg increased. There was no effect on the frequency of reference serum taken after an incident. While fewer incidents needed intervention, the total costs of HBV prevention still increased by 50%. Total costs increased by 13%, due to a shift in classification. CONCLUSIONS: The use of the new protocol facilitated standardized risk assessment for blood exposure accidents. HBIg administration and source testing decreased. An increased proportion of high-risk classifications resulted in an increase in the associated costs.

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PMID: 20453643 Bisschops LL, Hoedemaekers CW, Simons KS, van der Hoeven JG. Preserved metabolic coupling and cerebrovascular reactivity during mild hypothermia after cardiac arrest. Crit Care Med. 2010 Jul;38(7):1542-7. OBJECTIVE: Although mild hypothermia improves outcome in patients after out-of-hospital cardiac arrest, the cardiodepressive effects of hypothermia may lead to secondary brain damage. This study was performed to assess the cerebral blood flow, cerebral oxygen extraction, and cerebrovascular reactivity to changes in partial pressure of carbon dioxide in the arterial blood in comatose patients after out-of-hospital cardiac arrest treated with mild hypothermia. DESIGN: Observational study. SETTING: Tertiary care university hospital. PATIENTS: Ten comatose patients after out-of-hospital cardiac arrest. INTERVENTIONS: All patients were cooled to 32-34 degrees C for 24 hrs. Cerebrovascular reactivity to changes in carbon dioxide in the arterial blood was measured after increasing or decreasing the minute ventilation by 20%. MEASUREMENTS AND MAIN RESULTS: Mean flow velocity in the middle cerebral artery and pulsatility index were measured by transcranial Doppler at 0, 3, 6, 9, 12, 18, 24, and 48 hrs after admission. Jugular bulb oxygenation was measured at the same intervals. Cerebrovascular reactivity to changes in carbon dioxide in the arterial blood was studied on admission to the intensive care unit and at 6, 12, 18, and 24 hrs by measurement of mean flow velocity in the middle cerebral artery and jugular bulb oxygenation. Mean flow velocity in the middle cerebral artery was low (30.3+/-9.5 cm/sec) on admission and remained relatively stable for the first 24 hrs. After rewarming, it increased to 67.5+/-33.0 cm/sec at 48 hrs after admission from 30.3+/-9.5 at admission (p=.009). Jugular bulb oxygenation at the start of the study was 66.2+/-8.5% and gradually increased to 82.9+/-4.9% at 48 hrs (p<.001). Regression analysis showed a significant correlation between changes in carbon dioxide in the arterial blood, mean flow velocity in the middle cerebral artery (p<.001) and jugular bulb oxygenation (p<.001). The mean percentage change in mean flow velocity in the middle cerebral artery was 3.6+/-2.9% per 1-mm Hg change of carbon dioxide in the arterial blood. CONCLUSIONS: The mean flow velocity in the middle cerebral artery, as a parameter of cerebral blood flow, was low during mild hypothermia, whereas cerebral oxygen extraction remained normal, suggesting decreased cerebral metabolic activity. We demonstrated that CO2 reactivity is preserved during hypothermia in these patients.

PMID: 20456775 Tiessen RG, Lagerwey HJ, Jager GJ, Sprenger HG. Drug interaction caused by communication problems. Rhabdomyolysis due to a combination of itraconazole and simvastatin. Ned Tijdschr Geneeskd. 2010;154(14):A762. A 58-year-old man, who spoke very little Dutch, had various symptoms and used several drugs including simvastatin. He was prescribed itraconazole for onychomycosis. Simvastatin was concurrently replaced with pravastatin to prevent drug interactions. However, the interaction still occurred when the pravastatin ran out, and the patient resumed taking simvastatin on his own initiative. Myalgia and muscle weakness developed after one week. The general practitioner found a strongly elevated creatine kinase level in the blood. The patient required hospitalisation for severe rhabdomyolysis. He was treated with an infusion of an ample quantity of physiological saline solution and made a full recovery. Due to the elevated risk of toxic interactions, doctors should beware of communication problems in complex patients and avoid new prescriptions not strictly required.


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PMID: 20456809 Leeuwenburgh MM, Bakker OJ, Gorzeman MP, Bollen TL, Seldenrijk CA, Go PM. Fewer unnecessary appendectomies following ultrasonography and CT. Ned Tijdschr Geneeskd. 2010;154(17):A869. OBJECTIVE: To evaluate the effect of the use of ultrasonography (US) and optional computed tomography (CT) or diagnostic laparoscopy on the percentage of unnecessary appendectomies in patients with suspected acute appendicitis. DESIGN: Prospective and comparison with a historical control group. METHOD: Following the introduction of ultrasound imaging as an initial step, the outcomes in all patients presenting with suspected appendicitis in the emergency department were prospectively collected during a period of 18 months (July 2006-December 2007). Results were compared to retrospectively collected data on all patients who had undergone appendectomy for acute appendicitis in 2001, before the introduction of this imaging investigation. RESULTS: Of the 312 consecutive patients in the emergency department with suspected acute appendicitis, the condition was excluded in 51 patients following clinical and laboratory investigation. The diagnostic algorithm was applied in 239 of the 261 patients (92%). All of them had initial US, followed by additional CT in 75 patients (31%) and diagnostic laparoscopy in 12 patients (5%). Appendectomy was performed in 130 patients, and 8 (6%) of the appendices were shown to be healthy following pathological investigation. Before the implementation of preoperative imaging 36 of the 170 appendices (21%) were healthy. Following the introduction of imaging techniques in accordance with the guideline there was a significant reduction in the percentage of unnecessary appendectomies (21% versus 6%; p < 0,001). The complete supplementary diagnostic algorithm had a positive and negative predictive value of respectively 90% and 98% for acute appendicitis. CONCLUSION: Structural implementation of US with optional CT and diagnostic laparoscopy in patients with suspected acute appendicitis resulted in a lower percentage of unnecessary appendectomies.

PMID: 20461799 Keus SH, Nijkrake MJ, Borm GF, Kwakkel G, Roos RA, Berendse HW, Adang EM, Overeem S, Bloem BR, Munneke M; ParkinsonNet Trial Study Group. (ter Bruggen JP) The ParkinsonNet trial: design and baseline characteristics. Mov Disord. 2010 May 15;25(7):830-7. The companion paper describes how implementation of professional networks (ParkinsonNet) may improve the quality and efficiency of allied health care in Parkinson’s disease (PD). We designed a cluster-randomized controlled trial to evaluate this ParkinsonNet concept for one allied health discipline, namely physical therapy. Here we describe the study design and baseline characteristics. The design fully complies with the CONSORT criteria. Sixteen regions in the Netherlands were randomly divided into eight experimental regions where a ParkinsonNet was implemented, and eight control regions where the organization of care was left unchanged (usual care). Participating patients were followed for 6 months to evaluate the implementation process, health benefits and costs of the intervention. In the ParkinsonNet regions, 46 therapists were trained and 358 patients were included. In the usual care regions, 341 patients were included. Baseline characteristics of participants in the ParkinsonNet and control clusters were comparable. With 699 participating patients, this is the largest allied health study in PD to date.

PMID: 20471793 Van Vugt R, Kruse RR, Sterkenburg SM, Fritschy WM, Moll FL.

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(Semi-)Closed Endarterectomy in Occlusive Aortoiliac Disease. Ann Vasc Surg. 2010 May 13. BACKGROUND: Evaluation of the long-term results of a (semi-) closed endarterectomy of the aortoiliac segment with the use of the arterial disobliteration device. METHODS: From 1984 until 2005, a total of 157 patients (mean age, 53 years) with aortoiliac occlusive disease underwent a (semi-)closed endarterectomy of the aortoiliac segment. The primary operation indication was disabling claudication in 60.5% and advanced symptoms of ischemia or gangrene in 39.5%. The (semi-) closed endarterectomy was performed in 75% through a standard left retroperitoneal approach. RESULTS: Mean follow-up time was 18.2 years. Primary patency was 96% after 5 and 92% after 10 years. Fourteen patients underwent a reintervention within 30 days. The operative 30-day mortality rate was 1.5%. A reintervention for recurrence of occlusive disease during follow-up was necessary in 22 patients. At follow-up after an average of 18.2 years, 105 patients were alive, with 52 not related deaths. CONCLUSION: Retroperitoneal (semi-) closed disobliteration, with the use of the arterial disobliteration device, of the aortoiliac segment for stenotic and occlusive vascular disease is a safe and successful procedure the results of which are comparable with the implantation of a vascular aortic prosthesis. We consider this technique a valuable tool in vascular surgery.

PMID: 20478029 De Brouwer SJ, Kraaimaat FW, Sweep FC, Creemers MC, Radstake TR, van Laarhoven AI, van Riel PL, Evers AW. Experimental stress in inflammatory rheumatic diseases: a review of psychophysiological stress responses. Arthritis Res Ther 2010;12(3):R89. INTRODUCTION: Stressful events are thought to contribute to the aetiology, maintenance and exacerbation of rheumatic diseases. Given the growing interest in acute stress responses and disease, this review investigates the impact of real-life experimental psychosocial, cognitive, exercise and sensory stressors on autonomic, neuroendocrine and immune function in patients with inflammatory rheumatic diseases. METHODS: Databases Medline, PsychINFO, Embase, Cinahl and Pubmed were screened for studies (1985 to 2009) investigating physiological stress responses in inflammatory rheumatic diseases. Eighteen articles met the inclusion criteria. RESULTS: Results suggest that immune function may be altered in response to a stressor; such alterations could contribute to the maintenance or exacerbation of inflammatory rheumatic diseases during stressful events in daily life. CONCLUSIONS: This review emphasizes the need for more experimental research in rheumatic populations with controlled stress paradigms that include a follow-up with multiple evaluation points, simultaneous assessment of different physiological stress systems, and studying factors contributing to specific physiological responses, such as stress appraisal.

PMID: 20482926 Bakker OJ, Go PM, Puylaert JB, Kazemier G, Heij HA; Werkgroup en klankbordgroup Guideline on diagnosis and treatment of acute appendicitis: imaging prior to appendectomy is recommended. Ned Tijdschr Geneeskd. 2010;154:A303. Every year, over 2500 unnecessary appendectomies are carried out in the Netherlands. At the initiative of the Dutch College of Surgeons, the evidence-based guideline on the diagnosis and treatment of acute appendicitis was developed.


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This guideline recommends that appendectomy should not be carried out without prior imaging. Ultrasonography is the recommended imaging technique in patients with suspected appendicitis. After negative or inconclusive ultrasonography, a CT scan can be carried out. Appendectomy is the standard treatment for acute appendicitis; this can be done either by open or laparoscopic surgery. The first choice treatment of appendicular infiltrate is conservative treatment.

PMID: 20486727 Tielemans MM, Eikendal T, Jansen JB, van Oijen MG. Identification of NSAID users at risk for gastrointestinal complications: a systematic review of current guidelines and consensus agreements. Drug Saf. 2010 Jun 1;33(6):443-53. NSAIDs are among the most often used drugs worldwide. Numerous NSAID users are at risk for developing gastrointestinal complications. The purpose of this review was to identify and stratify risk factors for gastrointestinal complications in NSAID users documented in guidelines and consensus agreements, and to collect recommendations regarding over-the-counter (OTC) NSAID use. To facilitate this, a PubMed search from 1 January 1999 until 1 March 2009 was performed, resulting in the inclusion of nine English-language guidelines in our analysis. Risk factors were defined as ‘definite’ if mentioned in all guidelines; otherwise they were defined as ‘controversial’ risk factors. ‘Definite’ risk factors were a history of (complicated) peptic ulcer disease, older age (cut-off range 60-75 years), concomitant anticoagulant or corticosteroid use and multiple NSAID use, including low-dose aspirin (acetylsalicylic acid). ‘Controversial’ risk factors were high-dose NSAID use, concomitant clopidogrel or selective serotonin reuptake inhibitor use, a history of gastrointestinal symptoms, rheumatoid arthritis disability and cardiovascular disease. Infection with Helicobacter pylori was identified as an additive risk factor. Risk factors in OTC NSAID users were difficult to identify in the current literature. Risk factors were not all uniformly present in analysed guidelines and consensus agreements. We identified a history of (complicated) peptic ulcer disease, older age, concomitant anticoagulant or corticosteroid use and multiple NSAID use, including low-dose aspirin, as definite gastrointestinal risk factors in NSAID users.

PMID: 20502287 Westerhuis ME, Visser GH, Moons KG, van Beek E, Benders MJ, Bijvoet SM, van Dessel HJ, Drogtrop AP, van Geijn HP, Graziosi GC, Groenendaal F, van Lith JM, Nijhuis JG, Oei SG, Oosterbaan HP, Porath MM, Rijnders RJ, Schuitemaker NW, Sopacua LM, van der Tweel I, Wijnberger LD, Willekes C, Zuithoff NP, Mol BW, Kwee A. Cardiotocography plus ST-analysis of the fetal electrocardiogram versus cardiotocography only for intrapartum monitoring: a randomised controlled trial. Obstet Gynecol. 2010 Jun;115(6):1173-80. OBJECTIVE: To estimate the effectiveness of intrapartum fetal monitoring by cardiotocography plus ST analysis using a strict protocol for performance of fetal blood sampling. METHODS: We performed a multicenter randomized trial among laboring women with a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation. Participants were assigned to monitoring by cardiotocography with ST analysis (index) or cardiotocography only (control). Primary outcome was metabolic acidosis, defined as an umbilical cord artery pH below 7.05 combined with a base deficit calculated in the extracellular fluid compartment above 12 mmol/L. Secondary outcomes were metabolic acidosis in blood, operative deliveries, Apgar scores, neonatal admissions, and hypoxic-ischemic encephalopathy. RESULTS: We randomly assigned 5,681 women to the two groups (2,832 index, 2,849 control). The fetal blood

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sampling rate was 10.6% in the index compared with 20.4% in the control group (relative risk 0.52; 95% [CI] 0.460.59). The primary outcome occurred 0.7% in the index compared with 1.1% in the control group (relative risk 0.70; 95% CI 0.38-1.28; number needed to treat 252). Using metabolic acidosis calculated in blood, these rates were 1.6% and 2.6%, respectively (relative risk 0.63; 95% CI 0.42-0.94; number needed to treat 100). The number of operative deliveries, low Apgar scores, neonatal admissions, and newborns with hypoxic-ischemic encephalopathy was comparable in both groups. CONCLUSION: Intrapartum monitoring by cardiotocography combined with ST analysis does not significantly reduce the incidence of metabolic acidosis calculated in the extracellular fluid compartment. It does reduce the incidence of metabolic acidosis calculated in blood and the need for fetal blood sampling without affecting the Apgar score, neonatal admissions, hypoxic-ischemic encephalopathy, or operative deliveries. LEVEL OF EVIDENCE: I.

PMID: 20516439 Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, van der Griend R, Lokhorst H, Sonneveld P; Dutch-Belgium Cooperative Group HOVON. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. 2010 ; 28 (19) :3160-6. PURPOSE: For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T. PATIENTS AND METHODS: A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points. RESULTS: An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-Ttreated patients compared with MP-treated patients a response (> or = partial response: 66% v 45%, respectively; P < .001; and > or = very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05). CONCLUSION: This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.

PMID: 20517939 Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen MP, van Doorn PA, Steyerberg EW, Jacobs BC. Prediction of respiratory insufficiency in Guillain-Barré syndrome. Ann Neurol. 2010 Jun;67(6):781-7. OBJECTIVE: Respiratory insufficiency is a frequent and serious complication of the Guillain-Barré syndrome (GBS). We aimed to develop a simple but accurate model to predict the chance of respiratory insufficiency in the acute stage of the disease based on clinical characteristics available at hospital admission. METHODS: Mechanical ventilation (MV) in the first week of admission was used as an indicator of acute stage respiratory


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insufficiency. Prospectively collected data from a derivation cohort of 397 GBS patients were used to identify predictors of MV. A multivariate logistic regression model was validated in a separate cohort of 191 GBS patients. Model performance criteria comprised discrimination (area under receiver operating curve [AUC]) and calibration (graphically). A scoring system for clinical practice was constructed from the regression coefficients of the model in the combined cohorts. RESULTS: In the derivation cohort, 22% needed MV in the first week of admission. Days between onset of weakness and admission, Medical Research Council sum score, and presence of facial and/or bulbar weakness were the main predictors of MV. The prognostic model had a good discriminative ability (AUC, 0.84). In the validation cohort, 14% needed MV in the first week of admission, and both calibration and discriminative ability of the model were good (AUC, 0.82). The scoring system ranged from 0 to 7, with corresponding chances of respiratory insufficiency from 1 to 91%. INTERPRETATION: This model accurately predicts development of respiratory insufficiency within 1 week in patients with GBS, using clinical characteristics available at admission. After further validation, the model may assist in clinical decision making, for example, on patient transfer to an intensive care unit.

PMID: 20521308 Van Koulil S, van Lankveld W, Kraaimaat FW, van Helmond T, Vedder A, van Hoorn H, Donders R, de Jong AJ, Haverman JF, Korff KJ, van Riel PL, Cats HA, Evers AW. Tailored cognitive-behavioral therapy and exercise training for high-risk patients with fibromyalgia. Arthritis Care Res (Hoboken). 2010 Oct;62(10):1377-85. OBJECTIVE: The treatment of patients with fibromyalgia (FM), a high-prevalence chronic pain condition with a high impact on both patients and society, poses a great challenge to clinicians due to a lack of effective treatments. In view of the large individual variability in outcome, selecting patients at risk of long-term dysfunction and offering tailored treatment may be promising for beneficial treatment effects. METHODS: High-risk patients were selected and classified into 2 groups (pain-persistence and pain-avoidance groups) and subsequently randomized in groups to either a treatment condition (TC) or a waiting list control condition (WLC). Treatment consisted of 16 sessions of cognitive-behavioral therapy (CBT) and exercise training in groups, tailored to the patient’s specific cognitive-behavioral pattern, delivered within 10 weeks. Physical and psychological functioning and impact of FM were assessed at baseline, posttreatment, and 6-month followup. Treatment effects were evaluated using a linear mixed model. RESULTS: The treatment effects were significant for all primary outcomes, showing significant differences in physical (pain, fatigue, and functional disability) and psychological (negative mood and anxiety) functioning, and impact of FM for the TC in comparison with the WLC. Effect sizes in the TC were overall large, and reliable change indices indicated a clinically relevant improvement among the TC. CONCLUSION: The presented results demonstrate for the first time that tailored CBT and exercise training for high-risk patients with FM is effective in improving short- and long-term physical and psychological functioning, indicating that tailoring treatment is likely to promote beneficial outcomes in FM and reduce the burden for patients and society.

PMID: 20553055 van der Linden CM, Jansen PA, van Marum RJ, Grouls RJ, Korsten EH, Egberts AC. Recurrence of adverse drug reactions following inappropriate re-prescription: better documentation, availability of information and monitoring are needed. Adverse drug reactions (ADRs) are a common, and often preventable, cause of hospital admission, especially in the elderly, and can occur during hospitalization. In this current opinion article, we present three cases of recurrence of a serious

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ADR due to re-prescription of a withdrawn medication that highlight the need for a system to prevent the undesirable re-prescription of medications withdrawn because of an ADR. In addition, we describe an electronic system that could help prevent undesirable re-prescription following an ADR. Such a system should document ADRs systematically at the patient level, make this information available to relevant healthcare providers and the patient, and flag re-prescription of the offending drug. The effectiveness and cost effectiveness of such a system would need to be determined. Drug Saf. 2010 Jul 1;33(7):535-8.

PMID: 20553058 Mannesse CK, van Puijenbroek EP, Jansen PA, van Marum RJ, Souverein PC, Egberts TC. Hyponatremia as an adverse drug reaction of antipsychotic drugs: a case-control study in VigiBase. Drug Safety. 2010; 33(7): 569-78. BACKGROUND: Hyponatraemia due to antipsychotic use is a potentially serious problem; however, it is not known whether it is an adverse drug reaction (ADR) to antipsychotic use or is due to the underlying psychiatric disease. OBJECTIVE: To estimate the strength of the association between antipsychotics and hyponatraemia or syndrome of inappropriate antidiuretic hormone secretion (SIADH), using information reported to the WHO Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre (UMC). SETTING: The WHO global individual case safety report database system (VigiBase) maintained by the UMC. STUDY DESIGN: Case-control study, with cases being reports of hyponatraemia/SIADH, and controls being reports of other ADRs. Each case was sampled with ten controls sequencing in time from the date the corresponding case was entered into the database. The potential contribution of the chemical structures and receptor affinity (dopaminergic and/or serotonergic) of the antipsychotics was studied, as was the influence of concomitant use of other medications known to cause hyponatraemia. MAIN OUTCOME MEASURES: The strength of the association between antipsychotic use and hyponatraemia in comparison with other drugs was expressed as reporting odds ratio (ROR), a measure of disproportionality, with corresponding 95% CIs, adjusted for age, sex and concomitant medication associated with hyponatraemia. In addition, stratification by the presence or absence of concomitant medication was performed. RESULTS: Up to August 2008, 3 881 518 suspected ADRs were reported and filed in VigiBase, with 912 reports on hyponatraemia related to antipsychotics. The adjusted ROR for the association between antipsychotic use and hyponatraemia was 1.58 (95% CI 1.46, 1.70). The adjusted RORs did not vary for the different chemical structures or dopamine D(2) and serotonin 5-HT(2A) receptor affinity profiles. The ROR was 3.00 (95% CI 2.65, 3.39) for the association between hyponatraemia and antipsychotic use in the absence of concomitant medication associated with hyponatraemia, and 1.16 (95% CI 1.06, 1.28) in the presence of concomitant medication associated with hyponatraemia. CONCLUSIONS: Antipsychotic use may be associated with reporting of hyponatraemia. Moreover, the concomitant use of medication associated with hyponatraemia potentially leads to under-reporting of antipsychotic-associated hyponatraemia. We advise testing patients whose psychiatric and/or physical condition deteriorates while on antipsychotics for hyponatraemia.

PMID: 20570559 Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-smallcell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26.


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BACKGROUND: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and rearranged during transfection (RET) tyrosine kinases. In a randomised phase 2 study in patients with previously treated non-small-cell lung cancer (NSCLC), adding vandetanib 100 mg to docetaxel significantly improved progression-free survival (PFS) compared with docetaxel alone, including a longer PFS in women. These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC). METHODS: Between May, 2006, and April, 2008, patients with locally advanced or metastatic (stage IIIB-IV) NSCLC after progression following first-line chemotherapy were randomly assigned 1:1 through a third-party interactive voice system to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m(2) intravenously every 21 days; maximum six cycles) or placebo plus docetaxel. The primary objective was comparison of PFS between the two groups in the intention-to-treat population. Women were a coprimary analysis population. This study has been completed and is registered with ClinicalTrials.gov, number NCT00312377. FINDINGS: 1391 patients received vandetanib plus docetaxel (n=694 [197 women]) or placebo plus docetaxel (n=697 [224 women]). Vandetanib plus docetaxel led to a significant improvement in PFS versus placebo plus docetaxel (hazard ratio [HR] 0.79, 97.58% CI 0.70-0.90; p<0.0001); median PFS was 4.0 months in the vandetanib group versus 3.2 months in placebo group. A similar improvement in PFS with vandetanib plus docetaxel versus placebo plus docetaxel was seen in women (HR 0.79, 0.62-1.00, p=0.024); median PFS was 4.6 months in the vandetanib group versus 4.2 months in the placebo group. Among grade 3 or higher adverse events, rash (63/689 [9%] vs 7/690 [1%]), neutropenia (199/689 [29%] vs 164/690 [24%]), leukopenia (99/689 [14%] vs 77/690 [11%]), and febrile neutropenia (61/689 [9%] vs 48/690 [7%]) were more common with vandetanib plus docetaxel than with placebo plus docetaxel. The most common serious adverse event was febrile neutropenia (46/689 [7%] in the vandetanib group vs 38/690 [6%] in the placebo group). INTERPRETATION: The addition of vandetanib to docetaxel provides a significant improvement in PFS in patients with advanced NSCLC after progression following first-line therapy.

PMID: 20578923 Lensvelt MM, Brokelman WJ, Ivarsson ML, Falk P, Reijnen MM. Peritoneal transforming growth factor beta-1 expression during prolonged laparoscopic procedures. J Laparoendosc Adv Surg Tech A. 2010 Jul-Aug;20(6):545-50. BACKGROUND: Laparoscopic surgery may affect peritoneal physiology. Short-term laparoscopic surgery does not affect peritoneal transforming growth factor beta (TGF-b1) expression. The current study was conducted to evaluate the hypothesis that prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression. STUDY DESIGN: In the first study, 24 patients scheduled for a right colonic resection were enrolled in the trial. Twelve underwent conventional surgery (CCR) and 12 were operated on laparoscopically (LCR). In the second study, 12 patients undergoing laparoscopic gastric bypass (LGB) surgery for morbid obesity were included. Biopsies of the parietal peritoneum were taken at standardized moments during the procedures. Tissue concentrations of active and total TGF-b1 were measured by using enzyme-linked immunosorbent assays. RESULTS: During the LCR, there was a significant increase in peritoneal active TGF-b1 levels (P < 0.05). A similar, but not significant, trend was observed during the CCR. A similar pattern was seen in the total TGF-b1 concentrations during both procedures. The LGB procedure did not affect peritoneal active or total TGF-b1 concentrations. During the procedure, both the active and total TGF-b1 levels were significantly higher in the LCR, when compared to the LGB, group (P < 0.05). CONCLUSIONS: Prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression, depending on the procedure performed. Considering the role of TGF-b1 in various biologic processes, including adhesiogenesis and oncology, these results may have clinical consequences.

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PMID: 20585080 van der Linden CMJ, Jansen PAF, van Marum RJ, Grouls RJE, Egberts ACG, Korsten HHM. Reasons for discontinuation of medication during hospitalization and documentation thereof: a descriptive study of 400 geriatric and internal medicine patients. Arch Int Med. 2010 Jun 28;170(12):1085-7. PMID: 20593742 Wouters CJ, Dautzenberg L, Thissen A, Dautzenberg PL. Oral galantamine versus rivastigmine transdermal patch: a descriptive study at a memory clinic in The Netherlands. Tijdschr Gerontol Geriatr. 2010 Jun;41(3):146-50. OBJECTIVES: Since January 2008 in The Netherlands, two cholinesterase inhibitors, oral galantamine and rivastigmine transdermal patch, are registered as a one-day symptomatic treatment for Alzheimer’s disease. As no head to head study was performed yet, the objective of this study was to describe the daily practice of oral galantamine and rivastigmine transdermal patch in a real life population of a memory clinic of a suburban teaching hospital in The Netherlands. METHODS: A randomized open label study in 84 ambulant Alzheimer’s patients with at least 6 months follow-up and treated either with oral galantamine (group G) or rivastigmine transdermal patch (group R). Data collection included patients’ demographic and disease variables. Adverse events were collected and, in case of interruption of the primary treatment, the alternative treatment was registered. RESULTS: Serious adverse events did not occur. In group G respectively group R adverse events occurred in 20 patients (50%) and 18 patients (41%). No difference occurred in the frequency of nausea or vomiting. In group R more patients noted dermatological adverse events. In group G respectively group R medication was stopped in 12 patients (30%) and 14 patients (32%). However, compared to group G after stopping the treatment in group R more patients received a new anti-dementia medication (respectively 11 patients (79%) and 4 patients (33%)) (chi2(1) = 5.418, p = .026). CONCLUSION: Despite different forms, the use of oral galantamine and rivastigmine transdermal patch showed neither difference in the frequency of adverse events neither in the frequency of stopping primary treatment. However, compared to oral galantamine use, rivastigmine transdermal patch resulted in more dermatological adverse events and after stopping rivastigmine transdermal patch, new anti-dementia medication or form was more often started. More research is urgently needed.

PMID: 20601906 Schatorjé E, Hoekstra H. Transient hypertransaminasemia in paediatric patients with crohn disease undergoing initial treatment with enteral nutrition. J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):336-40. OBJECTIVES: Total enteral nutrition (TEN) is frequently used as monotherapy in children with Crohn disease to prevent steroid toxicity. Liver disease is a known complication in inflammatory bowel disease, and liver enzymes are regularly obtained in these patients. PATIENTS AND METHODS: Prospective follow-up of liver enzymes was performed in 11 new consecutive patients ages 7.6 to 17.1 years who were primarily treated with TEN for 6 weeks. Liver enzymes were measured before starting TEN and after 3, 6, and 12 weeks. RESULTS: At the beginning of TEN, the mean aspartate aminotransferase (ASAT) was 18.4 U/L and the mean alanine


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aminotransferase (ALAT) 17.1 U/L. The mean ASAT and ALAT were 202.0 U/L and 269.0 U/L after 3 weeks and 109.6 U/L and 180.9 U/L at 6 weeks. After 12 weeks values decreased to 22.8 U/L (ASAT) and 20.9 U/L (ALAT). Overall, 9 of 11 patients had transient elevated ASAT and 10 patients showed elevated ALAT. Gamma-glutamyl transpeptidase was slightly elevated in 3 patients during therapy, but alkaline phosphatase and bilirubin showed no changes. None of the patients developed liver disease during follow-up, and prolonged clinical remission was achieved in 9 patients. CONCLUSIONS: This study shows that TEN can be associated with transient hypertransaminasemia without evidence of liver disease. We hypothesise that insulin resistance in patients with Crohn disease in combination with standard TEN formulae can result in transient hepatic steatosis causing the hypertransaminasemia. For the clinician it is important to be aware of this benign TEN-associated condition to prevent unnecessary investigations.

PMID: 20619027 Bax L, Mail WP, Beutler JJ. Stenting in patients with atherosclerotic renal artery stenosis. Ned Tijdschr Geneeskd. 2010;154(23):A1607. PMID: 20619049 Van der Hoek W, Dijkstra F, Rietveld A, Wijkmans CJ, Steenbergen JE, Notermans DW, Schneeberger PM. Three years of Q fever in the Netherlands: faster diagnosis. [Drie Jaar Q-koorts in Nederland: snellere diagnose.] Ned Tijdschr Geneeskd 2010; 154:A1845. OBJECTIVE: To assess if more rapid diagnosis and treatment is possible and to assess if this could be improved, since the first outbreak of Q fever in 2007. DESIGN: Retrospective study of secondary data. METHODS: Analysis of surveillance data regarding Q fever over the period 2007 to 2009 and additional information on some patients from 2007 and 2008 obtained from general practitioners. RESULTS: Diagnostic delay fell sharply between 2007 and 2009 and to a lesser extent, so did therapeutic delay from 2007 to 2008. In high incidence areas, diagnosis and treatment was faster with a lower proportion of patients admitted to hospital than in low incidence areas. CONCLUSION: It appears that familiarity with the condition leads to faster diagnosis coupled with a lower percentage of hospital admissions. In order to react quickly it is necessary that doctor and patient should be aware of Q fever, especially in areas of low incidence. Polymerase chain reaction diagnostic techniques should also be available.

PMID: 20628482 Hermans E, van Schaik PM, Prins HA, Ernst MF, Dautzenberg PJ, Bosscha K. Outcome of colonic surgery in elderly patients with colon cancer. J Oncol. 2010;2010:865908. Introduction. Colonic cancer is one of the most commonly diagnosed malignancies and most often occurs in patients aged 65 years or older. Aim. To evaluate the outcome of colonic surgery in the elderly in our hospital and to compare five-year survival rates between the younger and elderly patients. Methods. 207 consecutive patients underwent surgery for colon cancer. Patients were separated in patients younger than 75 and older than 75 years. Results. Elderly patients presented significantly more (P < .05) as a surgical emergency, had a longer duration of admission

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and were more often admitted to the ICU (P < .01). Also, elderly patients had significant more co-morbidities, especially cardiovascular pathology (P < .01). Post-operative complications were seen more often in the elderly, although no significant difference was seen in anastomotic leakage. The five-year survival rate in the younger group was 62% compared with 36% in the elderly (P < .05). DFS was 61% in the younger patients compared with 32% in the elderly (P < .05). Conclusion. Curative resection of colonic carcinoma in the elderly is well tolerated and age alone should not be an indication for less aggressive therapy. However, the type and number of co-morbidities influence post-operative mortality and morbidity.

PMID: 20633223 Boerjan M, Bluyssen SJ, Bleichrodt RP, van Weel-Baumgarten EM, van Goor H. Work-related health complaints in surgical residents and the influence of social support and job-related autonomy. Med Educ. 2010 Aug;44(8):835-44. METHODS: All (n = 400) Dutch residents in training in general surgery were sent validated self-report questionnaires. Odds ratios were calculated predicting health and exposure to long-term stress for gender, number of working hours, type of hospital, level of social support, job-related autonomy and training phase. The interactions between job-related autonomy and level of social support provided by consultants and colleagues, and all variables, were analysed. RESULTS: A total of 254 of 400 (64%) residents returned questionnaires that were eligible for analysis. Residents experienced more health complaints than the average member of the Dutch working population (4.0 versus 2.5; p = 0.000). Male and senior residents were significantly ‘healthier’ than female and junior residents, respectively. Social support by consultants was a strong predictor of health and social support by colleagues showed a significant interaction with gender. Women and residents in university hospitals experienced less social support by consultants than men and residents in general teaching hospitals. Residents working in university hospitals experienced lower levels of jobrelated autonomy and less support from colleagues in comparison with those working in general teaching hospitals. A working week of > 60 hours adversely affected health and job-related autonomy. CONCLUSIONS: Social support provided by consultants and colleagues, and job control, are important factors that interact with the work-associated, stress-related health of residents in training in general surgery. Residents report a greater number of health complaints than the average member of the working population, especially female and junior residents. General teaching hospitals seem to provide better support at work than university hospitals.

PMID: 20658794 Kröger E, van Marum RJ, Souverein P, Egberts TC. Discontinuation of cholinesterase inhibitor treatment and determinants thereof in the Netherlands: A retrospective cohort study. Drugs Aging. 2010 Aug 1;27(8):663-75. BACKGROUND: The cholinesterase inhibitors (ChEIs) rivastigmine and galantamine have been approved for the treatment of mild to moderate Alzheimer’s disease in the Netherlands. Differences between ChEIs regarding persistence or the use of effective doses in daily clinical practice have been observed. However, most studies assessing ChEI discontinuation and associated determinants have been conducted in North America and there is a lack of knowledge about ChEI discontinuation and its determinants in daily clinical practice in Europe. OBJECTIVES: To assess ChEI discontinuation in daily practice in the Netherlands and to seek its determinants, including suboptimal utilization.


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METHODS: A retrospective cohort study was performed using data from the Dutch PHARMO Record Linkage System. Included patients were aged > or =50 years at first dispensing of a ChEI, had a first dispensing of a ChEI between 1998 and 2008, had a prior medication history of 12 months and had at least one subsequent dispensing of any kind of medication. The proportion of patients who discontinued ChEIs over 3 years was determined. Cox regression was used to assess determinants for early (< or =6 months) discontinuation and, separately, for late discontinuation during a subsequent 30-month follow-up among those persisting with treatment for >6 months. RESULTS: At 6 months, 30.8% of 3369 study patients had discontinued ChEIs, compared with 59.0% after 3 years. Thirty-five percent of patients taking rivastigmine reached the WHO-defined daily dose compared with 80% taking galantamine. At 6 months, compared with regular-dose rivastigmine, low-dose rivastigmine or low-dose galantamine was associated with an increased risk of early discontinuation, whereas regular-dose galantamine was associated with a decreased risk, as was concurrent use of cardiac medications, drugs for Parkinson’s disease, propulsives, selective serotonin reuptake inhibitors and benzodiazepines. Associations of ChEI type/dose or co-medications with discontinuation among patients persisting for > 6 months differed somewhat from associations with discontinuation before 6 months. CONCLUSIONS: Fewer patients taking rivastigmine than those taking galantamine reached recommended doses. Furthermore, patients taking rivastigmine had an increased risk of early discontinuation compared with patients taking galantamine. Adverse effects leading to treatment intolerance and suboptimal utilization may have been contributing factors to these observed differences.

PMID: 20673157 Kleinpenning MM, Langewouters AMG, Kerkhof PCM van de, Greebe RJ. Severe pyoderma gangraenosum unresponsive to etanercept and adalimumab. J Dermatolog Treat. 2010 Aug 1. Abstract Background: A 74-year-old female with severe and therapy-resistant pyoderma gangrenosum (PG) was treated for more than 40 years with topical antibacterial ointments, topical and systemic corticosteroids, dapsone and azathioprine. Generally, immunosuppression is the mainstay of treatment of PG, but in our patient cyclosporine had to be discontinued because of significant serious side effects. An attempt was made to decrease the amount of steroids, but tapering of the prednisone dose resulted in relapses of PG. Observation: Off-label use of etanercept resulted in a temporary limited clinical improvement. After 6 months, initial clinical improvement reduced and adalimumab was started. Unfortunately, after 6 months of adalimumab no clinical improvement was seen. Therefore, systemic corticosteroids had to be continued with very good clinical results. Conclusion: In concordance with previous results of several other studies, reviews and case reports, we presume that possibly both etanercept and adalimumab could be excellent therapeutic alternatives in the treatment of PG. Unfortunately, the effectiveness of both etanercept and adalimumab were very limited in our case. Literature research revealed no other successful studies on the off-label use of other immunomodulators as an alternative treatment option for PG. However, infliximab or ustekinumab could be alternative treatment options.

PMID: 20686659 van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a New Human Polyomavirus Associated with Trichodysplasia Spinulosa in an Immunocompromized Patient. PLoS Pathog. 2010 Jul 29; 6(7): e1001024.

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The Polyomaviridae constitute a family of small DNA viruses infecting a variety of hosts. In humans, polyomaviruses can cause infections of the central nervous system, urinary tract, skin, and possibly the respiratory tract. Here we report the identification of a new human polyomavirus in plucked facial spines of a heart transplant patient with trichodysplasia spinulosa, a rare skin disease exclusively seen in immunocompromized patients. The trichodysplasia spinulosa-associated polyomavirus (TSV) genome was amplified through rolling-circle amplification and consists of a 5232-nucleotide circular DNA organized similarly to known polyomaviruses. Two putative “early” (small and large T antigen) and three putative “late” (VP1, VP2, VP3) genes were identified. The TSV large T antigen contains several domains (e.g. J-domain) and motifs (e.g. HPDKGG, pRb family-binding, zinc finger) described for other polyomaviruses and potentially involved in cellular transformation. Phylogenetic analysis revealed a close relationship of TSV with the Bornean orangutan polyomavirus and, more distantly, the Merkel cell polyomavirus that is found integrated in Merkel cell carcinomas of the skin. The presence of TSV in the affected patient’s skin was confirmed by newly designed quantitative TSV-specific PCR, indicative of a viral load of 10(5) copies per cell. After topical cidofovir treatment, the lesions largely resolved coinciding with a reduction in TSV load. PCR screening demonstrated a 4% prevalence of TSV in an unrelated group of immunosuppressed transplant recipients without apparent disease. In conclusion, a new human polyomavirus was discovered and identified as the possible cause of trichodysplasia spinulosa in immunocompromized patients. The presence of TSV also in clinically unaffected individuals suggests frequent virus transmission causing subclinical, probably latent infections. Further studies have to reveal the impact of TSV infection in relation to other populations and diseases.

PMID: 20691040 van de Wall BJ, Draaisma WA, Consten EC, van der Graaf Y, Otten MH, de Wit GA, van Stel HF, Gerhards MF, Wiezer MJ, Cense HA, Stockmann HB, Leijtens JW, Zimmerman DD, Belgers E, van Wagensveld BA, Sonneveld ED, Prins HA, Coene PP, Karsten TM, Klaase JM, Statius Muller MG, Crolla RM, Broeders IA; Dutch Diverticular Disease (3D) Collaborative Study Group. DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative treatment. A multicenter randomised clinical trial. BMC Surg. 2010 Aug 6;10:25. BACKGROUND: Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses.Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management.We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. METHODS/DESIGN: The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years) presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management). Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used. The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, ShortForm 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and


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total costs. The total follow-up will be three years. DISCUSSION: Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214), may be gathered within one and a half year.Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation.

PMID: 20699030 Wever PC, Arts CH, Groot CA, Lestrade PJ, Koning OH, Renders NH. Screening for chronic Q fever in symptomatic patients with an aortic aneurysm or prosthesis. Ned Tijdschr Geneeskd. 2010;154(28):A2122. A 76-year-old man was referred to the Emergency Department because of collapse, epigastric pain and nausea. The patient had been diagnosed with an infrarenal aneurysm of the abdominal aorta nine years earlier. His symptoms were attributed to an aortic-duodenal fistula originating from the aneurysm. The patient died despite placement of an aortic prosthesis. A hospital screening programme for chronic Q fever in patients with aortic aneurysm revealed chronic Q fever. Until recently, vascular infection with Coxiella burnetii was an unknown disease in the Netherlands. In view of the nonspecific clinical presentation, severity and therapeutic consequences of the disease, we advise screening for chronic Q fever in all symptomatic patients with an aortic aneurysm or prosthesis - whether or not with aspecific symptoms - in regions where the disease is endemic.

PMID: 20693886 Dorresteijn MJ, Visser T, Cox LA, Bouw MP, Pillay J, Koenderman AH, Strengers PF, Leenen LP, van der Hoeven JG, Koenderman L, Pickkers P. C1-esterase inhibitor attenuates the inflammatory response during human endotoxemia. Crit Care Med. 2010 Nov;38(11):2139-45. OBJECTIVE: Besides its role in regulation of the complement and contact system, C1-esterase inhibitor has other immunomodulating effects that could prove beneficial in patients with acute inflammation such as during sepsis or after trauma. We examined the immunomodulating properties of C1-esterase inhibitor during human experimental endotoxemia, in which the innate immune system is activated in the absence of activation of the classic complement pathway. DESIGN: Double-blind placebo-controlled study. SETTING: Research intensive care unit of the Radboud University Nijmegen Medical Centre. SUBJECTS: Twenty healthy volunteers. INTERVENTIONS: Intravenous injection of 2 ng/kg Escherichia coli lipopolysaccharide. Thirty minutes thereafter (to prevent binding of lipopolysaccharide), C1-esterase inhibitor concentrate (100 U/kg, n = 10) or placebo (n = 10) was infused. MEASUREMENTS AND MAIN RESULTS: Pro- and anti-inflammatory mediators, markers of endothelial and complement activation, hemodynamics, body temperature, and symptoms were measured. C1-esterase inhibitor reduced the release of proinflammatory cytokines as well as C-reactive protein (peak levels of: interleukin-6 1521 ± 209 vs. 932 ± 174 pg/mL [p = .04], tumor necrosis factor-± 1213 ± 187 vs. 827 ± 167 pg/mL [p = .10], monocyte chemotactic protein-1 6161 ± 1302 vs. 3373 ± 228 pg/mL [p = .03], interleukin-1β 34 ± 5 vs. 23 ± 2 pg/mL [p < .01], Creactive protein 39 ± 4 vs. 29 ± 2 mg/L [p = .02]). In contrast, release of the anti-inflammatory cytokine interleukin-10 was increased by C1-esterase inhibitor (peak level 73 ± 11 vs. 121 ± 18 pg/mL, p = .02). The increase in

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interleukin-1 receptor antagonist tended to be smaller in the C1-esterase inhibitor group, but this effect did not reach statistical significance (p = .07). Markers for endothelial activation were increased after lipopolysaccharide infusion, but no significant differences between groups were observed. The lipopolysaccharide-induced changes in heart rate, blood pressure, body temperature, and symptoms (all p < .001 over time) were not influenced by C1-esterase inhibitor. Complement fragment C4 was not increased after lipopolysaccharide challenge. CONCLUSIONS: This study is the first to demonstrate that C1-esterase inhibitor exerts anti-inflammatory effects in the absence of classic complement activation in humans.

PMID: 20698878 Anderwald C, Ankersmit HJ, Badaoui A, Beneduce L, Buko VU, Calo LA, Carrero JJ, Chang C-Y, Chang K-C, Chen Y-J, Cnotliwy M, Costelli P, Crujeiras AB, Cuocolo A, Davis PA, de Boer OJ, Ebenbichler CF, Erridge C, Fassina G, Felix SB, García-Gomez MC, Guerrero-Romero F, Haider DG, HeinemannA, Herda LR, Hoogeveen EK, Hörl WH, Iglseder B, Huang K-C, Kaser S, Kastrati A, Kuzniatsova N, Latella G, Lichtenauer M, Lin Y-K, Lip GYH, Lu N-H, Lukivskaya O, Luschnig P, Maniscalco M, Martinez JA, MüllerKrebs S, Ndrepepa G, Nicolaou G, Peck-Radosavljevic M, Penna F, Pinto X, Reiberger T, Rodriguez-Moran M, Schmidt A, Schwenger V, Spinelli L, Starkel P, Stehouwer CDA, Stenvinkel P, Strasser P, Suzuki H, Tschoner A, van der Wal AC, Vesely DL, Wen C-J, Wiernicki I, Zanninelli G and Zhu Y. Research update for articles published in EJCI in 2008. Eur J Clin Invest. 2010; 40: 770-790. PMID: 20703938 Van der Sangen MJ, van de Wiel FM, Poortmans PM, Tjan-Heijnen VC, Nieuwenhuijzen GA, Roumen RM, Ernst MF, Tutein Nolthenius-Puylaert MC, Voogd AC. Are breast conservation and mastectomy equally effective in the treatment of young women with early breast cancer? Long-term results of a population-based cohort of 1,451 patients aged
PMID: 20732915 Van Santvoort HC, Besselink MG, Bakker OJ, Vleggaar FP, Timmer R, Weusten BL, Gooszen HG; Dutch Pancreatitis Study Group.


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Endoscopic necrosectomy in necrotising pancreatitis: indication is the key. Gut. 2010 Nov;59(11):1587. PMID: 20739731 van der Horn G, Ranschaert ER, Dubelaar IJ, van Munster IP. An adult with vague abdominal complaints and atypical colonoscopic findings. Neth J Med. 2010 Aug;68(1):324-7. PMID: 20798200 Tieleman AA, Knoop H, van de Logt AE, Bleijenberg G, van Engelen BG, Overeem S. Poor sleep quality and fatigue but no excessive daytime sleepiness in myotonic dystrophy type 2. J Neurol Neurosurg Psychiatry. 2010 Sep;81(9):963-7. BACKGROUND: In myotonic dystrophy type 1 (DM1), sleep disorders are common, with excessive daytime sleepiness (EDS) as a predominant feature. In myotonic dystrophy type 2 (DM2), the presence of sleep disturbances is unknown. OBJECTIVE: To investigate the frequency of EDS, poor sleep quality and fatigue in DM2. METHODS: 29 genetically proven DM2 patients were surveyed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Checklist Individual Strength. The results were compared with 29 adult onset DM1 patients and 65 population controls, both matched for age and sex. RESULTS: Only 6.9% of DM2 patients had EDS compared with 44.8% of DM1 patients and 6.2% of population controls (DM2-DM1: p=0.001; DM2-controls: p=0.51). Sleep quality was poor (PSQI >5) in both DM2 and DM1 groups, and differed significantly from population controls (DM2 6.5+/-3.0; DM1 6.2+/-3.7; controls 4.3+/-3.0; DM2-controls: p=0.002). Poor sleep quality was not explained by depression or other comorbidity but was mainly due to sleep disturbances as a result of nocturnal pain. Comparable with the DM1 group, DM2 patients experienced severe fatigue (DM2 38.7+/-13.1; DM1 42.9+/-8.5; controls 21.1+/-11.1; DM2-controls: p<0.001). Results were not confounded by abnormal thyroid function or medication use. CONCLUSION: These results provide new insight into the phenotype of DM2 and have consequences for clinical treatment. In addition, the absence of EDS in DM2 is a new discriminative feature with adult onset DM1.

PMID: 20802011 Limonard GJ, Peters JB, Nabuurs-Franssen MH, Weers-Pothoff G, Besselink R, Groot CA, Dekhuijzen PN, Vercoulen JH. Detailed analysis of health status of Q fever patients 1 year after the first Dutch outbreak: a case-control study. QJM 2010 Dec;103(12):953-8. BACKGROUND: Q fever is a zoonosis caused by the obligate intracellular bacterium Coxiella burnetii. The two longterm complications, after primary infection, are chronic Q fever in ∼1% of patients, and a chronic fatigue syndrome in 10-20%. However, the existence of a protracted decreased health status after Q fever remains controversial. AIM: To determine the health status of the patients of the Q fever outbreak in The Netherlands in 2007, 1 year after primary infection. DESIGN: Cross-sectional case-control study. METHODS: Health status of the patients from the 2007 Dutch Q fever outbreak was compared to age-, sex- and geographically matched and Q fever seronegative controls. Health status of both patients and controls was assessed

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with the Nijmegen Clinical Screening Instrument (NCSI). RESULTS: Fifty-four Q fever patients provided 34 years of age- and sex-matched controls from the same neighbourhood. Eleven controls had positive Q fever serology and were excluded. Q fever patients had significantly more problems on the subdomains of symptoms and functional impairment. Overall quality of life was decreased in both patients and controls, 59% vs. 39%, respectively, ns). Severe fatigue levels were present in 52% of patients vs. 26% in controls (P < 0.05). CONCLUSION: These data support a sustained decrease in many aspects of health status in Q fever patients in The Netherlands, 1 year after primary infection.

PMID: 20804340 Brandes M, Hamilton CJ, Bergevoet KA, de Bruin JP, Nelen WL, Kremer JA. Origin of multiple pregnancies in a subfertile population. Acta Obstet Gynecol Scand. 2010 Sep;89(9):1149-54. OBJECTIVE: To evaluate the contribution of different subfertility treatments to the number of multiple pregnancies in a subfertile population. DESIGN: A prospective cohort study between January 2002 and December 2006. SETTING: A subfertility clinic in a large regional training hospital in the Netherlands. POPULATION: A total of 1,001 continuing pregnancies, of which 63 (6.3%) were multiple. METHODS: Of all pregnancies, mode of conception, outcome and type of pregnancy (singleton or multiple) were documented. MAIN OUTCOME MEASURES: Proportions of continuing and multiple pregnancies caused by the different modes of conception. RESULTS: Of all subfertility related continuing pregnancies, 46% were conceived spontaneously, 16% were induced by clomiphene citrate (CC), 2.4% by follicle stimulating hormone (FSH) and 14% by intra-uterine insemination combined with controlled hyperstimulation (IUI/(COH)). In vitro fertilization (IVF) and its related techniques resulted in about a fifth of all continuing pregnancies (n = 212), but were responsible for more than half (n = 36) of the multiple pregnancies. Furthermore, 18% of the multiple pregnancies were induced by IUI/(COH), 3% by FSH, 11% by CC, whereas about 11% were conceived spontaneously. CONCLUSIONS: IVF and intra-cytoplasmic sperm injection (ICSI) were responsible for the majority of the multiple pregnancies in a subfertile population. Therefore, twin prevention should be focused on further promoting elective single embryo transfer (eSET). Fertility treatment and particular IVF should not be started as long as the spontaneous pregnancy prognosis is good.

PMID: 20814323 Kleijer BC, Heerdink R, Egberts ACG, Jansen PAF, van Marum RJ. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients. J Clin Psychopharmacol. 2010; Oct;30(5):526-30. OBJECTIVE: Our aim was to investigate the relationship between exposure to antipsychotic drugs and the risk of venous thromboembolism (VTE) in elderly patients. METHODS: A time-matched case-control analysis nested within a cohort of 111,818 patients with at least 1 antipsychotic drug prescription during 1998 to 2008. Data were used from the PHARMO institute’s database, which contains drug dispensing data from community pharmacies and hospital admission data. The index date was for the


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cases defined as the date of hospital admission for VTE (deep venous thrombosis [DVT] or pulmonary embolism) or, for outpatient cases, the start of therapeutic dose low-molecular weight heparin therapy. For each case, 4 controls matched by age and sex were randomly sampled from the cohort. MEASUREMENTS: Two measures were used to evaluate the temporal relationship between antipsychotic drug use and the occurrence of VTE: being a current, recent, or past user and the duration of use up to the index date. The strength of the association was expressed as odds ratios with 95% confidence intervals, taking into account potential confounders. RESULTS: We identified 367 cases of hospital admission for DVT, 342 cases of hospital admission for PE, and 323 cases of outpatient treatment of DVT. Current exposure to antipsychotic drugs was not associated with an increased risk of VTE, compared with nonusers (odds ratio, 0.9; 95% confidence interval, 0.7-1.1). We found no association between dosage, the duration of use, or the type of antipsychotic drug and the risk of VTE. CONCLUSIONS: We found no evidence of an increased risk of VTE in elderly patients using antipsychotic drugs.

PMID: 20816127 De Groot PC, Thijssen D, Binkhorst M, Green DJ, Schokking M, Hopman MT. Vascular function in children with repaired tetralogy of Fallot. Am J Cardiol. 2010 Sep 15;106(6):851-5. We compared the endothelial function and vascular wall characteristics of 11 children with tetralogy of Fallot (TOF) (age 13 +/- 3 years) with the characteristics of 17 age-matched peers (12 +/- 2 years). Echocardiographic Doppler measurements were performed under standardized conditions to assess (1) the carotid and femoral artery diameter and intimamedia thickness, (2) brachial artery endothelial function using flow-mediated dilation, and (3) central and peripheral compliance using pulsewave velocity. In addition, the physical activity level was assessed using a validated questionnaire. We found that the physical activity level of the children with TOF was lower than that of the controls, but the difference did not reach statistical significance (4.5 vs 5.9 h/wk, p = 0.087). A significantly larger femoral artery intima-media thickness was observed in those with TOF, and the carotid and brachial artery diameter and intima-media thickness were comparable between groups. The children with TOF demonstrated a significantly lower brachial artery flow-mediated dilation than that of the controls. The central and peripheral compliance did not differ between the 2 groups. In conclusion, children with TOF demonstrated an impaired brachial artery endothelial function and increased intima-media thickness of the femoral artery compared to their healthy peers. In conclusion, our findings have, therefore, indicated that children with TOF, already at a young age, have changes in vascular function and structure.

PMID: 20822723 Koebrugge B, van Wensen RJ, Bosscha K, Dautzenberg PL, Koning OH. Delirium after Emergency/Elective Open and Endovascular Aortoiliac Surgery at a Surgical Ward with a High-standard Delirium Care Protocol. Vascular. 2010 Sep-Oct;18(5):279-87. Delirium is a common problem in elderly patients undergoing surgery. Standard delirium care is not available at all surgical wards. We determined the incidence, risk factors, and outcomes of postoperative delirium among patients undergoing elective/emergency aortoiliac surgery at a surgical ward with high-standard delirium care. A prospective descriptive survey in 107 patients was conducted. High-standard delirium care was given to patients above age 65, consisting of an extended focus on risk factors and intensive screening. The Delirium Observation Scale was used as a screening instrument for delirium. Patients were classified as having delirium if they met the DSM-IV criteria. The overall incidence of delirium was 23%. The incidence was 14% after elective surgery. Delirium occurred in 59% after emergency

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surgery and more often after open than after endovascular aneurysm repair (p < .01). Delirium was associated with age (p < .01) and emergency surgery (p = .01) and is an important and frequent complication after aortoiliac surgery.

PMID: 20826645 Tilburg JJ, Melchers WJ, Pettersson AM, Rossen JW, Hermans MH, van Hannen EJ, Nabuurs-Franssen MH, de Vries MC, Horrevorts AM, Klaassen CH. Interlaboratory evaluation of different extraction and real-time PCR methods for the detection of Coxiella burnetii DNA in serum. J Clin Microbiol. 2010 Nov;48(11):3923-7. In the Netherlands, there is an ongoing and unparalleled outbreak of Q fever. Rapid and reliable methods to identify patients infected with Coxiella burnetii, the causative agent of Q fever, are urgently needed. We evaluated the performance of different DNA extraction methods and real-time PCR assays that are in use in seven diagnostic or reference laboratories in the Netherlands. A low degree of variation in the sensitivities of most of the developed realtime PCR assays was observed. However, PCR assays amplifying short DNA fragments yielded better results than those producing large DNA fragments. With regard to DNA extraction, the automated MagNA Pure Compact system and the manual QIAamp DNA mini kit consistently yielded better results than either the MagNA Pure LC system and NucliSens EasyMag (both automated) or the High Pure viral nucleic acid kit (manual). The present study shows that multiple combinations of DNA extraction kits and real-time PCR assays offer equivalent solutions to detect C. burnetii DNA in serum samples from patients suspected to have Q fever.

PMID: 20840759 Huijsmans CJ, Damen J, van der Linden JC, Savelkoul PH, Hermans MH. Comparative analysis of four methods to extract DNA from paraffin-embedded tissues: effect on downstream molecular applications. BMC Res Notes. 2010 Sep 14;3:239. BACKGROUND: A large portion of tissues stored worldwide for diagnostic purposes is formalin-fixed and paraffin-embedded (FFPE). These FFPE-archived tissues are an extremely valuable source for retrospective (genetic) studies. These include mutation screening in cancer-critical genes as well as pathogen detection. In this study we evaluated the impact of several widely used DNA extraction methods on the quality of molecular diagnostics on FFPE tissues. FINDINGS: We compared 4 DNA extraction methods from 4 identically processed FFPE mammary-, prostate-, colonand lung tissues with regard to PCR inhibition, real time SNP detection and amplifiable fragment size. The extraction methods, with and without proteinase K pre-treatment, tested were: 1) heat-treatment, 2) QIAamp DNA-bloodmini-kit, 3) EasyMAG NucliSens and 4) Gentra Capture-Column-kit.Amplifiable DNA fragment size was assessed by multiplexed 200-400-600 bp PCR and appeared highly influenced by the extraction method used. Proteinase K pretreatment was a prerequisite for proper purification of DNA from FFPE. Extractions with QIAamp, EasyMAG and heattreatment were found suitable for amplification of fragments up to 400 bp from all tissues, 600 bp amplification was marginally successful (best was QIAamp). QIAamp and EasyMAG extracts were found suitable for downstream real time SNP detection. Gentra extraction was unsuitable. Hands-on time was lowest for heat-treatment, followed by EasyMAG. CONCLUSIONS: We conclude that the extraction method plays an important role with regard to performance in downstream molecular applications.


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PMID: 20848574 Rutten MJ, Collins JM, de Waal Malefijt MC, Kiemeney LA, Jager GJ. Unsuspected sonographic findings in patients with post-traumatic shoulder complaints. J Clin Ultrasound. 2010 Nov;38(9):457-65. PURPOSE: To prospectively assess the frequency of abnormal sonographic findings in patients with posttraumatic shoulder pain and/or disability in whom ultrasound (US) was not considered and to assess the effect of sonographic findings on working diagnosis and therapeutic strategy, to analyze the possible role of US in the diagnostic workup of these patients. METHODS: A survey was performed under general practitioners and orthopedic surgeons. They were requested to refer patients with persistent posttraumatic complaints for an US examination of the shoulder and to fill out a questionnaire concerning working diagnosis and therapy. In 50 patients examinations were performed separately by two radiologists. Findings were confirmed with additional radiographs and/or MRI and/or surgery. Four weeks after the US examination, the survey was repeated to inquire about changes in diagnosis and/or treatment that resulted from US. RESULTS: US showed relevant pathology in 45 (90%) of 50 patients, a proximal humerus fracture in 25 (50%) patients, and a rotator cuff tear in 43 (86%) patients. Twenty-three (92%) fractures were accompanied by a rotator cuff tear, and 23 (54%) rotator cuff tears were accompanied by a fracture. Ten fractures were initially missed radiographically. US findings changed the working diagnosis and therapeutic strategy in 37 (74%) and 26 (52%) patients, respectively. CONCLUSION: In patients with posttraumatic shoulder complaints, US showed a high rate (90%) of relevant pathology. This changed the initial working diagnosis in 74% of the patients and the therapeutic strategy in more than half of the patients. Active referral for US examination may identify these abnormalities in an earlier phase and improve clinical outcome.

PMID: 20857313 Limonard GJ, Nabuurs-Franssen MH, Weers-Pothoff G, Wijkmans C, Besselink R, Horrevorts AM, Schneeberger PM, Groot CA. One-year follow-up of patients of the ongoing Dutch Q fever outbreak: clinical, serological and echocardiographic findings. Infection 2010 Dec;38(6):471-7. PURPOSE: In 2007, a large goat-farming-associated Q fever outbreak occurred in the Netherlands. Data on the clinical outcome of Dutch Q fever patients are lacking. The current advocated follow-up strategy includes serological follow-up to detect evolution to chronic disease and cardiac screening at baseline to identify and prophylactically treat Q fever patients in case of valvulopathy. However, serological follow-up using commercially available tests is complicated by the lack of validated cut-off values. Furthermore, cardiac screening in the setting of a large outbreak has not been implemented previously. Therefore, we report here the clinical outcome, serological follow-up and cardiac screening data of the Q fever patients of the current ongoing outbreak. METHODS: The implementation of a protocol including clinical and serological follow-up at baseline and 3, 6 and 12 months after acute Q fever and screening echocardiography at baseline. RESULTS: Eighty-five patients with acute Q fever were identified (male 62%, female 38%). An aspecific, flu-like illness was the most common clinical presentation. Persistent symptoms after acute Q fever were reported by 59% of patients at 6 months and 30% at 12 months follow-up. We observed a typical serological response to Coxiella burnetii infection in both anti-phase I and anti-phase II IgG antibodies, with an increase in antibody titres up to 3 months and a subsequent decrease in the following 9 months. Screening echocardiography was available for 66 (78%) out of 85 Q fever patients. Cardiac valvulopathy was present in 39 (59%) patients. None of the 85 patients developed chronic Q fever.

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CONCLUSIONS: Clinical, serological and echocardiographic data of the current ongoing Dutch Q fever outbreak cohort are presented. Screening echocardiography is no longer part of the standard work-up of Q fever patients in the Netherlands.

PMID: 20858325 Wegdam-Blans MC, Nabuurs-Franssen MH, Horrevorts AM, Peeters MF, Schneeberger PM, Bijlmer HA. Laboratory diagnosis of acute Q fever. [Laboratoriumdiagnostiek van acute Q-koorts.] Ned Tijdschr Geneeskd 2010;154:A2388. In the Netherlands an increasing number of laboratories are involved in diagnosing acute Q-fever. More uniformity in diagnostics and interpretation is desirable. To enable this, a working group on diagnostics of acute Q-fever was created on the initiative of the National Institute for Public Health and the Environment (RIVM) and the Dutch Association for Medical Microbiology (NVMM). The diagnostics of acute Q-fever includes a diagnostic flow chart (algorithm) consisting of tests for DNA and for antibodies against the antigens that appear in the successive stages of the disease. Reporting of both confirmed and suspected cases of acute Q-fever is obligatory.

PMID: 20890214 Hoekstra JH, van der Weij AM, Groot-Loonen J, Hoogerbrugge P, Kooy Y, Koning F. Succesful treatment of celiac disease by allogeneic haematopoietic stem cell transplantation. J Pediatr Gastroenterol Nutr 2010;51:793-4. PMID: 20948216 Koebrugge B, van Leuken M, Ernst MF, van Munster I, Bosscha K. Percutaneous Cholecystostomy in Critically Ill Patients with a Cholecystitis: A Safe Option. Dig Surg. 2010 Oct 15;27(5):417-421. Background: Cholecystectomy is the standard procedure in patients with acute cholecystitis. However, some patients might not be able to undergo immediate surgery because of severe sepsis or underlying comorbid conditions. Percutaneous cholecystostomy is a minimally invasive radiological procedure under local anesthesia which seems to be an effective alternative to conservative treatment or immediate laparoscopic/open cholecystectomy. Methods: We retrospectively analyzed 35 patients who underwent percutaneous cholecystostomy between 2003 and 2009. Results: Percutaneous cholecystostomy was technically successful in all patients. Symptoms resolved within 3 days in 33/35 patients. Two patients needed an emergency laparotomy. The catheter dislodged in 5 patients and was replaced in 2/5. The 30-day mortality rate was 3/35 (8.7%) due to gallbladder necrosis, myocardial infarction and multiorgan failure. Median length of hospital stay was 17 days and median drainage time was 28 days. 23 patients (66%) underwent open or laparoscopic cholecystectomy after a median interval of 44 days. Conclusion: Percutaneous cholecystostomy is an effective procedure and a good alternative for patients unfit to undergo immediate surgery because of severe sepsis or underlying comorbid conditions, preferably followed by interval cholecystectomy to prevent recurrent cholecystitis.

PMID: 20955571 Swank HA, Vermeulen J, Lange JF, Mulder IM, van der Hoeven JA, Stassen LP, Crolla RM, Sosef MN, Nienhuijs SW, Bosker RJ, Boom MJ, Kruyt PM, Swank DJ, Steup WH, de Graaf EJ, Weidema WF, Pierik RE, Prins HA, Stockmann HB, Tollenaar RA, van Wagensveld BA, Coene PP, Slooter GD, Consten EC, van Duijn EB, Gerhards MF, Hoofwijk AG, Karsten TM, Neijenhuis PA, Blanken-Peeters CF, Cense HA, Mannaerts GH, Bruin SC, Eijsbouts QA, Wiezer MJ, Hazebroek EJ, van Geloven AA, Maring JK, D’Hoore AJ, Kartheuser A,


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Remue C, van Grevenstein HM, Konsten JL, van der Peet DL, Govaert MJ, Engel AF, Reitsma JB, Bemelman WA; Dutch Diverticular Disease (3D) Collaborative Study Group. The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann’s procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037). BMC Surg. 2010 Oct 18;10:29. BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann’s procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann’s procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis.

PMID: 21034463 de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care. 2010;14(5):R192. INTRODUCTION: Absolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients. METHODS: We retrospectively evaluated the ability of conventional infection markers, lymphocyte count and NLCR to predict bacteremia in adult patients admitted to the Emergency Department with suspected community-acquired bacteremia. The C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count and NLCR were compared between patients with positive blood cultures (n = 92) and age-matched and gender-matched patients with negative blood cultures (n = 92) obtained upon Emergency Department admission. RESULTS: Significant differences between patients with positive and negative blood cultures were detected with respect to the CRP level (mean ± standard deviation 176 ± 138 mg/l vs. 116 ± 103 mg/l; P = 0.042), lymphocyte count (0.8 ± 0.5 × 109/l vs. 1.2 ± 0.7 × 109/l; P < 0.0001) and NLCR (20.9 ± 13.3 vs. 13.2 ± 14.1; P < 0.0001) but not

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regarding WBC count and neutrophil count. Sensitivity, specificity, positive and negative predictive values were highest for the NLCR (77.2%, 63.0%, 67.6% and 73.4%, respectively). The area under the receiver operating characteristic curve was highest for the lymphocyte count (0.73; confidence interval: 0.66 to 0.80) and the NLCR (0.73; 0.66 to 0.81). CONCLUSIONS: In an emergency care setting, both lymphocytopenia and NLCR are better predictors of bacteremia than routine parameters like CRP level, WBC count and neutrophil count. Attention to these markers is easy to integrate in daily practice and without extra costs.

PMID: 21040534 Munster JM, Leenders AC, van der Hoek W, Schneeberger PM, Rietveld A, Riphagen-Dalhuisen J, Stolk RP, Hamilton CJ, de Vries E, Meekelenkamp J, Lo-Ten-Foe JR, Timmer A, De Jong-van den Berg LT, Aarnoudse JG, Hak E. Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial. BMC Womens Health. 2010 Nov 1;10(1):32. BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cutoff level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy.

PMID: 21067384 de Vries EN, Prins HA, Crolla RM, den Outer AJ, van Andel G, van Helden SH, Schlack WS, van Putten MA, Gouma DJ, Dijkgraaf MG, Smorenburg SM, Boermeester MA; SURPASS Collaborative Group. Effect of a comprehensive surgical safety system on patient outcomes. N Engl J Med. 2010 Nov 11;363(20):1928-37. BACKGROUND: Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved


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by targeting the entire surgical pathway. METHODS: We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals. RESULTS: In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals. CONCLUSIONS: Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care.

PMID: 21069528 Rutten MJ, de Jong MD, van Loon T, Jager GJ. Intratendinous ganglion of the long head of the biceps tendon: US and MRI features (2010: 9b). Intratendinous ganglion. Eur Radiol. 2010 Dec;20(12):2997-3001. We present a case report and literature review of the ultrasound (US) and magentic resonance imaging (MRI) features of an intratendinous ganglion originating from the long head of the biceps tendon. Intratendinous ganglia are very rare entities and intratendinous ganglion of the long head of the biceps tendon has only been described once. To the best of our knowledge, this is the first case report presenting the sonographic features of an intratendinous ganglion originating from the long head of the biceps tendon.

PMID: 21087542 Dijkstra F, Riphagen-Dalhuisen J, Wijers N, Hak E, van der Sande MA, Morroy G, Schneeberger PM, Schimmer B, Notermans DW, van der Hoek W. Antibiotic therapy for acute Q fever in The Netherlands in 2007 and 2008 and its relation to hospitalization. Epidemiol Infect 2010 Nov 19:1-10. SUMMARYData about the effectiveness of different antibiotic regimens for the treatment of acute Q fever from clinical studies is scarce. We analysed the antibiotic treatment regimens of acute Q fever patients in 2007 and 2008 in The Netherlands and assessed whether hospitalization after a minimum of 2 days antibiotic therapy was related to the initial antibiotic therapy. Clinical data on antibiotic treatment and risk factors of acute Q fever patients were obtained from general practitioner medical records and self-reported by patients. For the 438 study patients, doxycycline was the most commonly prescribed initial antibiotic in both study years. After adjustments for confounding factors, doxycycline (200 mg/day), moxifloxacin, as well as other possibly effective antibiotics [including other new fluoroquinolones and doxycycline (100 mg/day)] showed significant lower risks for hospitalization compared to β-lactam antibiotics and azithromycin (reference group), with the lowest risk for doxycycline (200 mg/day) (odds ratio 0·04, 95% confidence

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interval 0·01-0·22). These data support current guidelines that recommend doxycycline as the first choice antibiotic for treating acute Q fever.

PMID: 21209466 Kampschreur LM, Wegdam-Blans MC, Thijsen SF, Groot CA, Schneeberger PM, Hollander AA, Schijen JH, Arents NL, Oosterheert JJ, Wever PC. Acute Q fever related in-hospital mortality in the Netherlands. Neth J Med 2010 Dec;68(12):408-413. INTRODUCTION: A large outbreak of acute Q fever has been reported in the Netherlands with over 3500 cases from 2007 to 2009, during which 749 patients were hospitalised. In foreign cohorts, reported mortality rates in patients hospitalised with acute Q fever, ranged from 0.9 to 2.4%. We analysed mortality among hospitalised patients with acute Q fever in the Netherlands. METHODS: Physicians from hospitals in the afflicted region were asked to provide details about patients who died with a diagnosis of acute Q fever between 2007 and 2009. RESULTS: Nine patients (seven males, median age 72 years) from six hospitals were reported, who died within approximately one month following hospitalisation for acute Q fever. Six definite acute Q fever cases and three probable cases were identified. Six patients presented with infiltrates on the chest X-ray and a median CURB-65 score of 3. Median time of hospitalisation was 13 days (range 1-33). All patients had serious, often coinciding, underlying conditions including chronic cardiovascular disease, chronic lung disease, diabetes mellitus and malignancy. CONCLUSION: The mortality rate of patients hospitalised because of acute Q fever was estimated at approximately 1%. Patients who died with acute Q fever were often male, of older age, and had chronic coinciding underlying conditions, which gives an a priori higher risk of death.


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Publicaties. Ziekenhuis s-hertogenbosch Onder redactie van: Wetenschapscommissie Wetenschapsbureau

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