Wetenschappelijk jaaroverzicht 2012

Wetenschappelijk jaaroverzicht 2012

Wetenschappelijk jaaroverzicht 2012

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Inhoud

Samenstelling Wetenschapscommissie

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Woord vooraf

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Wetenschappelijk jaarverslag Wetenschapscommissie 2012

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Wetenschappelijk jaaroverzicht per vakgroep 2012

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Anesthesiologie

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Cardiologie 17 Chirurgie 22 Dermatologie 32 Facilitair bedrijf

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Gynaecologie 35 Interne geneeskunde

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Keel, neus en oorheelkunde

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Kindergeneeskunde 51 Klinische chemie

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Klinische fysica

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Klinische geriatrie

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Leerhuis 59 Longgeneeskunde 62 Maag, darm en lever

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Medische microbiologie

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Neurologie 69 Orthopedie 72 Pathologie 73 Psychiatrie 79 Radiologie 80 Reumatologie 83 Spoedeisende geneeskunde

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Urologie 87 Ziekenhuisapotheek 88 Promoties ASz 2012

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Wetenschapsdag ASz 2012

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Mondelinge presentaties

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Poster presentaties

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Verantwoording 114

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Samenstelling Wetenschapscommissie

Dagelijks bestuur dr. M.C.J.M. Kock, voorzitter, radioloog dr. M-D Levin, vice-voorzitter, internist-hematoloog mw. C.N. van Waardhuizen MSc, beleidsadviseur mw. E.Y. de Kruyf, secretariaat

Overige leden 2012 dr. ir. B. van den Berg, klinisch fysicus dr. A. Bischoff, KNO-arts dr. E.F.H. van Bommel, internist-nefroloog drs. R.P.M. Ceulen, dermatoloog Prof. Dr. A.J.M. Cleophas, internist t/m 30 april drs. L.P.L.H. Cuijpers, klinisch psycholoog dr. M.A. Fouraux, klinisch chemicus dr. H.M.E. Frenay, arts-microbioloog mw. R. van Hof, medisch informatiespecialist drs. A.M. van der Velden, arts-assistent spoedeisende geneeskunde drs. A.D. Klaren, manager Leerhuis & Kwaliteit, Veiligheid en Innovatie drs. S. Hendriks, intensivist-anesthesioloog dr. P.W. Plaisier, chirurg drs. J.M.M. van de Ridder, adviseur Medische Vervolgopleidingen Leerhuis dr. T.C.J. Sas, kinderarts dr. A.C. de Mol, kinderarts-neonatoloog drs. E.M. de Vogel, ziekenhuisapotheker dr. P.J. Westenend, patholoog dr. L.J.P.M. van Woerkens, cardioloog dr. D. Zemel, neuroloog drs. J. Alderliesten, MDL arts dr. D. Cheung, longarts drs. S. Rombout-de Weerd, gynaecoloog dr. N.B. Swarte, gynaecoloog

Hoofdredactie Wetenschappelijk tijdschrift ‘WASz’ drs. A.M. van der Velden, arts-assistent spoedeisende geneeskunde dr. N.B. Swarte, gynaecoloog

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Samenstelling Wetenschapscommissie

Woord vooraf

Voor u ligt het jaarverslag met een weergave van de wetenschappelijke activiteiten die in 2012 hebben plaatsgevonden in het Albert Schweitzer ziekenhuis (ASz). De activiteiten variëren van promoties en wetenschappelijke activiteiten tot voordrachten en posters met betrekking tot de (directe) patiëntenzorg. Onze professionals hebben ook dit jaar weer meer gepubliceerd dan vorig jaar en de variëteit in wetenschappelijk activiteiten onder verschillende beroepsgroepen in het ASz is eveneens toegenomen. Wij zijn tevreden met de wetenschappelijke output over 2012. Het zegt iets over de eigenschappen en deskundigheid van onze professionals. Dit alles om de kwaliteit en doelmatigheid van de patiëntenzorg te verbeteren. Dat neemt niet weg dat we als STZ ziekenhuis ook naar onze processen moeten blijven kijken. Om de wetenschappelijke onderzoekscultuur te bestendigen en om in de toekomst een volwaardig lid van de STZ vereniging te blijven, moeten we continue verder inzetten op het stimuleren en faciliteren van wetenschappelijk onderzoek. Naast het bieden van inhoudelijke ondersteuning bij het opzetten en uitvoeren van wetenschappelijk onderzoek, de organisatie van de jaarlijkse Wetenschapsdag en maandelijkse Wetenschapslunches, en het werken aan het stimuleren van onderzoek onder verpleegkundigen, gaat het om het stroomlijnen van processen, faciliteiten en verdere doorontwikkeling van het ASz Stipendium. Met de organisatie daarvan zijn we nu volop bezig en dit zal in 2013 leiden tot verdere concretisering. Langs deze weg willen we iedereen die, direct dan wel indirect, een bijdrage heeft geleverd aan het wetenschappelijk onderzoek in 2012 in het ASz hartelijk bedanken. Alleen al bij het doorbladeren van dit jaaroverzicht zult u merken dat er gestaag aan de weg getimmerd wordt en dat we trots mogen zijn op de onderzoeksresultaten. Een lijn die we ook naar de toekomst verder uit willen bouwen en vast zullen houden! De Wetenschapscommissie biedt u dit jaarverslag dan ook graag aan ter overzicht en inspiratie.

dr. M.C.J.M. Kock C.N. van Waardhuizen, MSc Voorzitter Wetenschapscommissie/Radioloog Beleidsadviseur Wetenschap

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Wetenschappelijk jaarverslag Wetenschapscommissie 2012

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Wetenschapscommissie In 2012 heeft de Wetenschapscommissie haar dienstverlening verder geprofessionaliseerd. In het beleidsplan “Zorg voor Wetenschap” heeft de Wetenschapscommissie haar visie op wetenschap geformuleerd en de lijnen naar de toekomst uitgezet. Begin 2012 werd echter duidelijk dat de doelstellingen uit het beleidsplan bijgesteld moesten worden naar aanleiding van het STZ rapport ‘Bibliometric analysis of STZ-hospitals’. Uit dit rapport is gebleken dat zowel kwaliteit als kwantiteit nog verder verbeterd konden worden. Daarnaast beschikt het ASz over een beperkt wetenschappelijk netwerk in vergelijking met andere STZ ziekenhuizen. Om met elkaar een strategie te bedenken om het wetenschappelijk onderzoek in het ASz beter uit de verf te laten komen is er in september 2012 een Heidag Wetenschap “Wetenschap in het ASz op weg naar beter” georganiseerd. In aanloop naar de Heidag Wetenschap zijn een aantal knelpunten betreffende het wetenschappelijk klimaat in het ASz benoemd. Deze knelpunten zijn aan de genodigden op de heidag wetenschap ASz voorgelegd om gezamenlijk een of meerdere oplossingsrichting(en) te bedenken en bespreken. Naast een interactief deel en plenaire discussies, omvatte het dagprogramma meerdere presentaties vanuit verschillende vakgroepen, RvB en Stafbestuur. Naar aanleiding van de Heidag Wetenschap ASz is een plan van aanpak opgesteld wat zich richt op een aantal strategische punten om het wetenschapsbeleid te verankeren in het ziekenhuisbeleid voor de komende vijf jaar. Dit houdt in dat er de komende tijd belangrijke acties genomen zullen moeten worden door diverse partijen.

Het Albert Schweitzer Stipendium Als topklinisch opleidingsziekenhuis wil het ASz (medisch) wetenschappelijk onderzoek van eigen bodem stimuleren en ondersteunen door middel van een wetenschapsfonds “Het Albert Schweitzer Stipdium”. Het Stipendium biedt onderzoekers de mogelijkheid zich (fulltime) bezig te houden met research activiteiten. Voor de financiële ondersteuning van in ASz geïnitieerd, eigen onderzoek is in 2012 tweemaal een Stipendiumronde gehouden. Het Stipendium is in 2012 toegekend aan de volgende studies/onderzoekers: Toegekende Albert Schweitzer Stipendium/gehonoreerde aanvragen 2012 De relatie tussen antenatale echografische Den Dekker

Kindergeneeskunde

diagnostiek naar nierafwijkingen en de postnatale bevindingen in het Albert Schweitzer ziekenhuis

Pelkmans

Interne geneeskunde

Sier

Chirurgie

Oskam

SEH

Retroperitoneale fibrose ISI trial en I-aid studie Pre-hospitale sepsis behandeling; verminderen van mortaliteit bij ernstige sepsis

Aantal verzoeken ingediend in 2012: 9 Aantal toegekend: 4

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WASz In 2012 verscheen onder hoofdredactie van drs. A. van der Velden en dr. N. Swarte tweemaal het Wetenschappelijk tijdschrift Albert Schweitzer ziekenhuis (WASz). Door middel van het tijdschrift worden medewerkers en verwijzers periodiek op de hoogte gehouden van allerlei wetenschappelijke activiteiten van het Albert Schweitzer ziekenhuis.

Cursussen De volgende cursussen werden in 2012 gegeven op het gebied van wetenschappelijk onderzoek; Cursus PubMed Poster maken Medical Writing in English Wetenschappelijk onderzoek inclusief SPSS

Wetenschapsdag 2012 Op donderdag 21 juni 2012 werd de ‘8e jaarlijkse Wetenschapsdag Albert Schweitzer ziekenhuis” gehouden in het Auditorium op de locatie Dordwijk. De wetenschapsdag van 21 juni was een succesvolle en goed bezochte dag met meer dan 100 bezoekers bestaande uit A(N)IOS, coassistenten, specialisten en verpleegkundigen. Bij ontvangst kregen de deelnemers het Wetenschappelijk Jaaroverzicht 2011 uitgereikt met daarin een uitgebreid overzicht per vakgroep van de wetenschappelijke output. De deelnemers ontvingen ook een abstractboek met daarin een overzicht van alle mondelinge – en posterpresentaties op de Wetenschapsdag. In zijn inleiding belichtte dr. Marc Kock, voorzitter van de Wetenschapscommissie, dat er in 2011 wederom meer PubMed publicaties waren dan in voorgaande jaren. Het verdere programma omvatte twee rondes van vier mondelinge presentaties waarin verteld werd over onderzoek dat in ons ziekenhuis verricht is. Na elke presentatie volgde een levendige discussie met de zaal. Daarnaast volgden twee rondes van posterpresentaties. Vele vakgroepen hadden een of enkele geaccepteerde inzendingen. De afwisseling in onderwerp was ook hierbij groot. De externe spreker, mw. dr. M.A.J. de Ridder van de afdeling biostatistiek van het Erasmus MC, heeft een boeiende presentatie gehouden over ‘het gevaar van multiple testing’. Tot slot heeft dr. Amerik de Mol een presentatie gehouden over zijn promotieonderzoek met betrekking tot Extracorporeale membraan oxygenatie en het brein. Prijs voor de beste publicatie 2011 ging naar Ewout-Jan van den Bos (Cardiologie) voor onderzoek naar de betekenis van troponine I stijging bij patiënten met atriumfibrilleren. De prijs voor de beste voordracht ging na publieksstemming naar Esther Leung (Klinische Fysica) met haar mooie multimediapresentatie over geluiden van apparaten op de IC. Het publiek verkoos de poster van Ashvin Boeddha (Orthopaedie) over het schrappen van preoperatieve

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bloedgroepbepalingen ten aanzien van mogelijke bloedtransfusie na totale knieprothese in het Albert Schweitzer ziekenhuis tot beste poster.

Wetenschappelijk spreekuur In de periode t/m mei 2012 heeft prof. dr. Cleophas het Wetenschappelijk spreekuur in het Asz gehouden. Wegens zijn pensionering is het Leerhuis van het ASz met ingang van 1 mei 2012 een driejarige samenwerking aangaan met de afdeling Biostatistiek van het Erasmus MC om het wetenschappelijk klimaat in het ASz naar een nog hoger niveau te brengen. Op dinsdagen van 9.00 tot 17.00 uur in de docentenkamer (op de 2e etage voor het vergadercentrum) op locatie Dordwijk zijn of mw. dr. Maria de Ridder of dr. Dimitris Rizopoulos aanwezig in het ASz voor een inloopspreekuur. Een enkele keer heeft dhr. Sten Willemsen het spreekuur in het ASz gehouden. Net als voorheen staat dit inloopspreekuur open voor iedereen die vragen heeft met betrekking tot het schrijven van een onderzoeksopzet, statistische methodes en rapportage van de resultaten. Daarnaast kan op de statistici van het Erasmus MC een beroep worden gedaan om analyses uit te voeren. In 2012 hebben circa 80 personen het inloopspreekuur bezocht.

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Wetenschappelijk jaaroverzicht 2012 per vakgroep

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Anesthesiologie

PubMed publicaties Designing a strategy to implement cost-effective blood transfusion management in elective hip and knee arthroplasties: A study protocol. Voorn VM, de Mheen PJ, So-Osman C, Vlieland TP, Koopman-van Gemert AWMM, Nelissen RG, van Bodegom-Vos L; for the LISBOA study group. Implement Sci. 2012 Jun 30;7(1):58. BACKGROUND: Total hip and knee arthroplasties are two of the most commonly performed procedures in orthopedic surgery. Different blood-saving measures (BSMs) are used to reduce the often-needed allogenic blood transfusions in these procedures. A recent large randomized controlled trial showed it is not cost effective to use the BSMs of erythropoietin and perioperative autologous blood salvage in elective primary hip and knee arthroplasties. Despite dissemination of these study results, medical professionals keep using these BSMs. To actually change practice, an implementation strategy is needed that is based on a good understanding of target groups and settings and the psychological constructs that predict behavior of medical professionals. However, detailed insight into these issuses is lacking. Therefore, this study aims to explore which groups of professionals should be targeted at which settings, as well as relevant barriers and facilitators that should be taken into acount in the strategy to implement evidence-based, cost-effective blood transfusion management and to de-implement BSMs. METHODS: The study consists of three phases. First, a questionnaire survey among all Dutch orthopedic hospital departments and independent treatment centers (n = 99) will be conducted to analyze current blood management practice. Second, semistructured interviews will be held among 10 orthopedic surgeons and 10 anesthesiologists to identify barriers and facilitators that are relevant for the uptake of cost-effective blood transfusion management. Interview questions will be based on the Theoretical Domains Interview framework. The interviews will be followed by a questionnaire survey among 800 medical professionals in orthopedics and anesthesiology (400 professionals per discipline) in which the identified barriers and facilitators will be ranked by frequency and importance. Finally, an implementation strategy will be developed based on the results from the previous phases, using principles of intervention mapping and an expert panel. DISCUSSION: The developed strategy for cost-effective blood transfusion management by de-implementing BSMs is likely to reduce costs for elective hip and knee arthroplasties. In addition, this study will lead to generalized knowledge regarding relevant factors for the de-implementation of non-cost-effective interventions and insight in the differences between implementation and de-implementation strategies. PMCID: PMC3443067 PMID: 22747693 [PubMed - as supplied by publisher]

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The Long-term Efficacy and Safety of Percutaneous Cervical Nucleoplasty in Patients with a Contained Herniated Disk. Halim W, Wullems JA, Lim T, Aukes HA, van der Weegen W, Vissers KC, Gültuna I, Chua NH. Pain Pract. 2012 Oct 31. [Epub ahead of print] BACKGROUND: Percutaneous cervical nucleoplasty (PCN) is a safe and effective treatment in symptomatic patients with contained cervical herniated disks. It provides simple and efficient disk decompression, using a controlled and highly localized ablation, but evidence regarding long-term efficacy is limited. We conducted a retrospective study to investigate the longterm efficacy and safety of PCN, and the influence of ideal selection settings. METHODS: A total of 27 patients treated with PCN fulfilling ideal selection criteria (Group A) were studied and compared to 42 patients not meeting these criteria (Group B). Outcomes were assessed using the Visual Analogue Scale (VAS) and a four-level Likert item for perceived pain and satisfaction, the Neck Disability Index (NDI), and the Short Form 36 (SF-36). Additional relevant outcomes were retrieved from medical records. RESULTS: The postoperative mean VAS pain for Group A was 29.9 (SD ± 32.6) at a mean follow-up of 24 months (range: 2-45). Only 10% of these patients reported mild transient adverse events. There was a trend, but no difference between both groups in pain scores; however, treatment satisfaction was higher for Group A (74.1 ± 27.2-55.5 ± 31.4, P = 0.02). Group A also reported better physical functioning based on the Physical Component Summary (43.6 ± 10.6-37.3 ± 12.0, P = 0.03) and showed a larger proportion of patients no longer using any medication postoperatively (63-26%, P = 0.01). CONCLUSION: These results show long-term effectiveness and safety of PCN in patients with a one-level contained cervical herniated disk, and the reliance of selecting patients meeting ideal criteria for successful PCN. PMID: 23113964 [PubMed - as supplied by publisher]

Pubmed collaborative authorship publicaties Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Collaborator: … Koopman-van Gemert AWMM … JAMA. 2012 Mar 21;307(11):1151-60. CONTEXT: Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort. OBJECTIVE: To determine the efficacy of dexmedetomidine vs midazolam or propofol(preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients’ interaction with nursing care. DESIGN, SETTING, AND PATIENTS: Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included

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Anesthesiologie

were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251). INTERVENTIONS: Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials. MAIN OUTCOME MEASURES: For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients’ ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223). RESULTS: Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients’ interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI,15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001). CONCLUSIONS: Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients’ ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00481312, NCT00479661. PMID: 22436955 [PubMed - indexed for MEDLINE]

Mortality after surgery in Europe: a 7 day cohort study. Pearse RM, Moreno RP, Bauer P, Pelosi P, Metnitz P, Spies C, Vallet B, Vincent JL, Hoeft A, Rhodes A; European Surgical Outcomes Study (EuSOS) group for the Trials groups of the European Society of Intensive Care Medicine and the European Society of Anaesthesiology. … Koopman-van Gemert AWMM … Lancet. 2012 Sep 22;380(9847):1059-65. BACKGROUND: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe. METHODS: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient noncardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ(2) and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U

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test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries. FINDINGS: We included 46,539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9-3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0-3·0] for Iceland to 21·5% [16·9-26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19-1·05; p=0·06]for Finland to 6·92 [2·37-20·27; p=0·0004] for Poland). INTERPRETATION: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients. FUNDING: European Society of Intensive Care Medicine, European Society of Anaesthesiology. PMCID: PMC3493988 PMID: 22998715 [PubMed - indexed for MEDLINE]

Boek of hoofdstuk in boek Autotransfusion: Therapeutic, Principles, Efficacy and Risks. Koopman-van Gemert AWMM. Chapter 12 in Blood transfusions in Clinical Practice, Puneet Kaur Kochhar editor, ISBN 978-953-51-0343-1, also as e-book http://www.intechopen.com/books/blood-transfusion-in-clinical-practice

A randomised controlled trial on erythropoietin and blood salvage as transfusion alternatives in orthopaedic surgery using a restrictive transfusion policy Cynthia So-Osman, MD, M Sc, Rob G H H Nelissen, MD, PhD, Koopman-van Gemert AWMM, MD, PhD, Ewoud Kluyver, MD, Ruud G Pöll, MD, PhD, Ron Onstenk, MD; Joost A Van Hilten, MD, PhD, Thekla M Jansen- Werkhoven, PhD, Wilbert B van den Hout, PhD, Ronald Brand, PhD and Anneke Brand, MD, PhD. In: Patient Blood Management in Elective Orthopaedic Surgery. Hoofdstuk 7 in Proefschrift Cynthia So-Osman. Oktober 2012.

Overige publicaties Autotransfusie. Therapeutische principes, efficiëntie en risico’s. Koopman-van Gemert AWMM A&I, 2012 ; 3 : 46-51

Reactie Commissie Juridische zaken van de Nederlandse Vereniging voor Anesthesiologie. Rubriek Ingezonden. Reacties op uitspraak van 6 januari 2011. Kop B. Tijdschrift voor gezondheidsrecht (TvGR) nr. 1-2012 p. 47-48.

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Anesthesiologie

Subcutaneous stimulation as an Additional Therapy to Spinal Cord Stimulation for the treatment of lower limb pain and/ or Back pain: A feasibility study. Hamm- Faber TE, Aukes HA, de Loos F and Gültuna I. Neuromodulation: Technology at the Neural Interface 2012; volume 15, p: 108 -117.

Posters Improving Patient Safety by Team Learning: a systems approach. Koopman-van Gemert AWMM et al., International Forum on Safety and Quality in Healthcare:17-20 april 2012, Paris.

Schrappen van preoperatieve bloedgroepbepalingen ten aanzien van mogelijke bloedtransfusie na totale knieprothese in het Albert Schweitzer Ziekenhuis. Boeddha AV, Koeveringen van AJ, Gelder van W, Breimer LTM Wetenschapsdag ASz. 12 juni 2012.

Bloedtransfusiebeleid 2004-2009: TOMaat- vs niet -TOMaat-patiënten. Koopman-van Gemert AWMM, Kuijpers AG, Mandl EW Wetenschapsdag ASz. 12 juni 2012

Implementation of a Rapid Response System decreases the number of in-hospital cardiac arrests in a large teaching hospital. So KL et al. International Forum on Safety and Quality in Healthcare, 17-20 april 2012, Paris France.

Implementation of a Rapid Response System decreases the number of in-hospital cardiac arrests in a large teaching hospital. So KL et al. NVIC dagen, 9-10 februari 2012, Ede.

Implementation of a Rapid Response System decreases the number of in-hospital cardiac arrests in a large teaching hospital. Koopman-van Gemert AWMM. International Forum on Quality and Safety in Healthcare, BMJ-IHI 17-20 april, Paris France.

First result of the PREPARE study. Prepare team, Koopman-van Gemert AWMM namens ASz. ESA, 9-12 juni 2012, Parijs Frankrijk.

A randomised controlled trial on erythropoietin and blood salvage as transfusion alternatives in orthopaedic surgery using a restrictive transfusion policy. So-Osman C, Nelissen RGHH, Koopman-van Gemert AWMM, Kluyver E, Pöll R, Onstenk R, Van Hilten JA, Jansen-Werkhoven TM, Brand R, Brand A. EFFORT congress, 23-25 May 2012, Berlin Germany.

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Voordrachten From Anatomy through Diagnostics to Best Practice in Advanced Neuromodulation Therapies, A hands on cadaver workshop for the experinced user. Gültuna I. European Continuing Medical Training(ECMT), 27 + 28 january 2012, Brussel Belgium.

Ervaringen met TRM op de Intensive Care. So KL. NVIC-dagen, 10 februari 2012, Ede.

VAR als motor voor kwaliteitsverbetering”. NVZ Netwerk “Patientveiligheid& verpleegkundige rol. So KL. NVZ dagen, 5 april 2012, Woerden.

Groot bloedverlies: alternatieven? Koopman-van Gemert AWMM. 3e refresher course Obstetrische Anesthesie, 18 april 2012, de Driehoek Utrecht.

Alternatieve strategieën voor pijnbestrijding: lachgas weer in de mode? Schyns-van den Berg AMJV. 3e refresher course Obstetrische Anesthesie, 18 april 2012, de Driehoek Utrecht.

Improving Patient Safety by Team Learning: a systems approach. Buljac – Samardzic M, Dekker – van Doorn CM, Huijsman R, Klein J, Koopman-van Gemert AWMM, Wauben LSGL, van Wijngaarden JDH. International Forum on Quality and Safety in Healthcare, 12-17 april 2012, Paris France.

“Mortality as a motor for quality improvement” So KL. Congres. Dag van de Herverzekeraars ASz Dordrecht. 12 oktober 2012 Dordrecht Pre-operatief Bloedmanagement Koopman-van Gemert AWMM. Symposoium Transfusiegeneeskunde, 18 oktober 2012 Boerhave Leiden

“Effectief teamfunctioneren en veiligheid in de zorg”. So KL Jaarlijkse arts-assistentendag “Risk Management” 25 oktober 2012, ASz Dordrecht. Advanced Neuromodulation training

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Anesthesiologie

Richtlijnen in de praktijk. Koopman-van Gemert AWMM. NVA dagen, 9-10 mei 2012, Maastricht.

Mortality as a motor for quality improvement. So KL. Reed congres ‘Patiëntveiligheid: niet later maar nu’, 22 mei 2012, Ede.

Patient Blood Management. Stand van zaken POP-I studie. Koopman-van Gemert AWMM. Depot Noord, 24 mei 2012, Rotterdam.

LISBOA-study. Marang-van de Mheen PJ, So-Osman C, Vliet Vlieland TPM, Koopman-van Gemert AWMM, Nelissen RGHH, Bodgom-Vos L. ISBT, 7-12 juli 2012 Cancun, Mexico.

Advanced Neuromodulation training. Gültuna I. Subcutaneous peripheral field stimulation technical aspects, 11-12 october 2012, Graz Austria.

Levenslang doorontwikkelen van medisch specialisten.door appraisal & assessment. So KL. NVMO 15-16 november 2012, Maastricht.

Hoe kan de medisch staf in algemene ziekenhuizen bij opleiden betrokken worden? van de Ridder JMM, Bommel EFH, Koopman-van Gemert AWMM, Oostenbroek RJ, Verheijen FM, Zanting A. NVMO congres, 15-16 november 2012, Maastricht.

Kinderanesthesie in een niet academische setting. Koopman-van Gemert AWMM. WKC, 17 november 2012, Utrecht.

Ervaringen met Rotem in het ASz. Koopman-van Gemert AWMM. Symposium Rotem, 23 november 2012, Hotel Mijdrecht Marickenland Mijdrecht.

Clinical and Basic Science for the management of the chronic pain patient. Gültuna I. Neuromodulation course cadaver workshop, 30 november- 1 december 2012, Barcelona.

Workshop “Expeditie 2015”. Koopman-van Gemert AWMM. Congres Modernisering Medische Vervolgopleidingen, 12 december 2012, NBC Nieuwegein.

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PubMed publicaties Bicuspid aortic valve with vertical opening and double raphe. Brugts JJ, Kurvers M, Kofflard MJ. Eur Heart J Cardiovasc Imaging. 2012 Jan;13(1):123. PMID: 22058088 [PubMed - in process]

Acute coronary syndrome in a patient with a single coronary artery arising from the right sinus of Valsalva. Liesting C, Brugts JJ, Kofflard MJ, Dirkali A. World J Cardiol. 2012 Aug 26;4(8):264-6. Coronary artery anomalies are usually encountered as coincidental findings during coronary angiography or at autopsy. Life threatening symptoms, such as arrhythmias, syncope, myocardial infarction, or sudden death, can occur in up to 20% of patients. However, the majority of anomalies (80%) are benign and asymptomatic. A single coronary artery (SCA) is one of the most rarely seen coronary anomalies with an incidence of 0.05%. We report the case of a 55-year old male patient who presented with symptoms of chest pain associated with an acute myocardial infarction. Coronary angiography revealed an anomalous left main coronary artery (LMCA) originating from the right coronary ostium, and an occluded distal right coronary artery. The occluded distal right coronary artery was successfully treated by thrombosuction and stenting. In order to confirm the origin and course of the SCA, multi-slice computed tomography (MSCT) of the heart was performed after coronary angiography. MSCT showed that the anomalous LMCA originated from the right coronary artery ostium and then passed the interventricular septum, instead of being intra arterial, and under the right ventricular infundibulum. The anomalous LMCA was classified as R-II S subtype according to Lipton’s classification. PMCID: PMC3432885 PMID: 22953025 [PubMed]

A rare case of massive papillary fibroelastoma of the right ventricular free wall. Baks T, Galema TW, Bakker J, Kofflard MJ. Neth Heart J. 2012 Aug;20(7-8):330-1. PMCID: PMC3402573 PMID: 21607675 [PubMed]

Right-to-left atrial shunting with normal intracardiac pressures following cardiac surgery: pathophysiology and management. Brugts JJ, Liesting C, Kofflard MJ, van den Bos EJ. J Card Surg. 2012 May;27(3):335-7.

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We present a case of acute respiratory insufficiency with right-to-left atrial shunting under normal intracardiac pressures discovered several days after aortic surgery for aortic dissection. We discuss the possible mechanisms and management of right-to-left atrial shunting through an atrial septum defect with normal intracardiac pressures following cardiac surgery. PMID: 22150888 [PubMed - indexed for MEDLINE]

Obstructive giant cardiac tumour in a patient with chest pain and acute respiratory insufficiency. Brugts JJ, van den Bos EJ, Raap JB, van de Woestijne PC, Kofflard MJ, Dirkali A. J Cardiovasc Med (Hagerstown). 2012 Apr;13(4):274-6. A 77-year-old woman presented with dyspnoea and respiratory-related thoracic pain, which was accompanied by dizziness and fatigue but no syncopal attacks. Auscultation of the heart disclosed an opening snap with mid-diastolic murmur. Laboratory assessment revealed no abnormalities but an elevated D-dimer level (1.49 mg/l). Electrocardiography was normal. The chest radiograph showed an enlarged heart without other abnormalities. Computed tomography (CT) scan for a suspected diagnosis of pulmonary embolism was performed. The CT scan did not reveal pulmonary embolism, but a large cardiac tumour in the left atrium. PMID: 22343258 [PubMed - indexed for MEDLINE]

Lack of long-term clinical benefit of thrombus aspiration during primary percutaneous coronary intervention with paclitaxel-eluting stents or bare-metal stents: post-hoc analysis of the PASSION-trial. Vink MA, Dirksen MT, Tijssen JG, Suttorp MJ, Patterson MS, van Geloven N, IJsselmuiden AJ, Slagboom T, Kiemeneij F, Laarman GJ. Catheter Cardiovasc Interv. 2012 May 1;79(6):870-7. BACKGROUND: Although current clinical guidelines recommend the use of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI), previous studies evaluating TA demonstrated contradictory results. The aim of this study was to evaluate long-term clinical outcome after TA in adjunct to PPCI for acute ST-segment myocardial infarction (STEMI), as compared with conventional treatment, with the use of paclitaxel-eluting stents or baremetal stents. METHODS: We analyzed data of the PASSION trial, in which 619 patients with STEMI were randomly assigned to a paclitaxel-eluting stent or a bare-metal stent. TA was performed in 311 patients (50.2%). Clinical endpoints at 2 years were compared between patients who received TA during PPCI with patients who underwent conventional PPCI. The primary outcome of interest was a composite of cardiac death, recurrent myocardial infarction (MI), or target-lesion revascularization (TLR). A propensity score model was made to account for baseline differences that could have affected the probability of performing TA. RESULTS: Complete follow-up was available for 598 patients (96.6%). The cumulative incidence of the combined outcome measure of cardiac death, recurrent MI, or TLR was 40 (13.0%) in the TA group and 41 (13.5%) in the conventional PPCI group (HR 0.96; 95% CI 0.62-1.47; P = 0.84). Also after adjusting for propensity score, no significant difference in event rate was observed between both treatment groups.

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CONCLUSIONS: In this post-hoc analysis of the PASSION trial, TA in adjunct to PPCI did not affect rates of major adverse cardiac events at 2 years follow-up, as compared with conventional PPCI. PMID: 21735533 [PubMed - indexed for MEDLINE]

Pubmed collaborative authorship publicaties n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. ORIGIN Trial Investigators, Bosch J, Gerstein HC, Dagenais GR, Díaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S. Collaborators: …Kurvers M, Stoel I… N Engl J Med. 2012 Jul 26;367(4):309-18. BACKGROUND: The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown. METHODS: In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here. RESULTS: During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups. CONCLUSIONS: Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events.(Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.). PMID: 22686415 [PubMed - indexed for MEDLINE]

Basal insulin and cardiovascular and other outcomes in dysglycemia. ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S. Collaborators: … Kurvers M, Stoel I… N Engl J Med. 2012 Jul 26;367(4):319-28.

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BACKGROUND: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. METHODS: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. RESULTS: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97). CONCLUSIONS: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.). PMID: 22686416 [PubMed - indexed for MEDLINE]

Overige publicaties Incidence of cardiotoxicity of trastuzumab in Her2Neu positive breast cancer: a single centre experience. Liesting C, Brugts JJ, Levin M-D, Kofflard MJM. Neth Heart J 2012;20 (Suppl):3.

Assessment of prognostic LV parameters with CMR in hypertrophic cardiomyopathy: impact of the papillary muscles. Gommans DHF, Bakker J, Cramer GE, Kurvers MJ, Brouwer MA, Verheugt FWA, Kofflard MJM. Journal of Cardiovascular Magnetic Resonance 2012;14 (Suppl 1): P 160.

Voordrachten Potential Damage to Early Endothelial Progenitor Cell Mobilization after Percutaneous Coronary Intervention Because of Amplified Mitochondrial Production of Reactive Oxygen Species in White Blood Cells. van Waardenburg J, IJsselmuiden AJJ, Riedl JA, Kofflard MJM. Wetenschapsdag ASZ 21 juni 2012 Dordrecht.

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Self-expanding stents in complex anatomy. IJsselmuiden AJJ. STENTYS CLINICAL FORUM III, 26/27 april 2012, Athene Griekenland.

Self-expanding Stenting Yields Improved Stent Strut Apposition Compared to Balloon Expandable stenting 3 Days after Primary Percutaneous Coronary Intervention, Hypothesised to Decrease Oxidative Stress and Increase Endothelial Progenitor Cell function. van Waardenburg J, IJsselmuiden AJJ, Dirkali A, Kulekci K, de Vries AG, on behalf of the Apposition investigators Geaccrediteerde Presentatie NVVC Voorjaarscongres, 12 april 2012, Noordwijkerhout.

Self-expanding stent in STEMI. IJsselmuiden AJJ. EuroPCR2012 congres, 17 mei 2012, Parijs Frankrijk.

APPOSITION III - Evaluation of the STENTYS self-apposing bare and drugeluting stent in 1000 STEMI patients in a real-life setting: in-hospital and 30-day outcomes. Amoroso G, Koch K, IJsselmuiden AJJ. EuroPCR2012 congres, 18 mei 2012, Parijs Frankrijk.

Incidence of cardiotoxicity of Trastuzumab in Her2Neu positive breast cancer: a single centre experience. Kofflard MJM. Najaarscongres NVVC, 4 oktober 2012, Papendal.

Beeldvorming bij Hypertrofische Cardiomyopathie. Kofflard MJM. Cardiovasculaire beeldvormingsavond georganiseerd door het CVOI, 11 oktober 2012, Vergadercentrum Hoog Brabant, Utrecht.

Posters Assessment of prognostic LV parameters with CMR in hypertrophic cardiomyopathy: impact of the papillary muscles. Gommans DHF, Bakker J, Cramer GE, Kurvers MJ, Brouwer MA, Verheugt FWA, Kofflard MJM. 15th Annual SCMR Scientific Sessions, Orlando Florida USA, 2-5 February 2012.

Short and Long Term Clinical Outcomes of Chronic Total Occlusion Treatment with a Latest Generation Drug Eluting Stent. Chauvet AA, Blank R, Dirkali A, Doshi S, Erglis A, Hsien-Li Kao P, Lotan C, Neskovic A, Polad J, Vlasenko S. TCT geaccrediteerd congres, 23 oktober 2012, Miami Verenigde Staten.

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Chirurgie

PubMed publicaties Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences. Kwast AB, Groothuis-Oudshoorn KC, Grandjean I, Ho VK, Voogd AC, Menke-Pluymers MB, van der Sangen MJ, Tjan-Heijnen VC, Kiemeney LA, Siesling S. Breast Cancer Res Treat. 2012 Jul 19. [Epub ahead of print] Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR- subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER-PR- patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78-1.06, >3 years HR 1.07, 95 % CI 0.88-1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences. PMID: 22810087 [PubMed - as supplied by publisher]

Comparison of 30-day, 90-day and in-hospital postoperative mortality for eight different cancer types. Damhuis RA, Wijnhoven BP, Plaisier PW, Kirkels WJ, Kranse R, van Lanschot JJ. Br J Surg. 2012 Aug;99(8):1149-54. BACKGROUND: Various definitions are used to calculate postoperative mortality. As variation hampers comparability between reports, a study was performed to evaluate the impact of using different definitions for several types of cancer surgery. METHODS: Population-based data for the period 1997-2008 were retrieved from the Rotterdam Cancer Registry for resectional surgery of oesophageal, gastric, colonic, rectal, breast, lung, renal and bladder cancer. Postoperative deaths were tabulated as 30-day, in-hospital or 90-day mortality. Postdischarge deaths were defined as those occurring after discharge from hospital but within 30 days. 22

RESULTS: This study included 40 474 patients. Thirty-day mortality rates were highest after gastric (8·8 per cent) and colonic (6·0 per cent) surgery, and lowest after breast (0·2 per cent) and renal (2·0 per cent) procedures. For most tumour types, the difference between 30-day and in-hospital rates was less than 1 per cent. For bladder and oesophageal cancer, however, the in-hospital mortality rate was considerably higher at 5·1 per cent (+1·3 per cent) and 7·3 per cent (+2·8 per cent) respectively. For gastric, colonic and lung cancer, 1·0 per cent of patients died after discharge. For gastric, lung and bladder cancer, more than 3 per cent of patients died between discharge and 90 days. CONCLUSION: The 30-day definition is recommended as an international standard because it includes the great majority of surgery-related deaths and is not subject to discharge procedures. The 90-day definition, however, captures mortality from multiple causes; although this may be of less interest to surgeons, the data may be valuable when providing information to patients before surgery. PMID: 22718521 [PubMed - in process]

A Hospital-Based Work Support Intervention to Enhance the Return to Work of Cancer Patients: A Process Evaluation. Tamminga SJ, de Boer AG, Bos MM, Fons G, Kitzen JJ, Plaisier PW, Verbeek JH, Frings-Dresen MH. J Occup Rehabil. 2012 Jun 15. [Epub ahead of print] PURPOSE: To perform a process evaluation of a hospital-based work support intervention for cancer patients aimed at enhancing return to work and quality of life. The intervention involves the delivery of patient education and support at the hospital and involves the improvement of the communication between the treating physician and the occupational physician. In addition, the research team asked patient’s occupational physician to organise a meeting with the patient and the supervisor to make a concrete gradual return-to-work plan. METHODS: Eligible were cancer patients treated with curative intent and who have paid work. Data were collected from patients assigned to the intervention group (N = 65) and from nurses who delivered the patient education and support at the hospital (N = 4) by means of questionnaires, nurses’ reports, and checklists. Data were quantitatively and qualitatively analysed. RESULTS: A total of 47 % of all eligible patients participated. Nurses delivered the patient education and support in 85 % of the cases according to the protocol. In 100 % of the cases at least one letter was sent to the occupational physician. In 10 % of the cases the meeting with the patient, the occupational physician and the supervisor took place. Patients found the intervention in general very useful and nurses found the intervention feasible to deliver. CONCLUSIONS: We found that a hospital- based work support intervention was easily accepted in usual psycho-oncological care but that it proved difficult to involve the occupational physician. Patients were highly satisfied and nurses found the intervention feasible. PMID: 22699884 [PubMed - as supplied by publisher]

Outcome of surgery for colovesical and colovaginal fistulas of diverticular origin in 40 patients. Smeenk RM, Plaisier PW, van der Hoeven JA, Hesp WL. J Gastrointest Surg. 2012 Aug;16(8):1559-65. Epub 2012 Jun 1.

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INTRODUCTION: According to literature, colonic resection with a primary anastomosis and no defunctioning ileostomy is a safe treatment for colovesical or colovaginal fistula of diverticular origin. This study investigates the outcome of surgery for this patient group in a regional hospital. METHODS: Patients were obtained from a prospective database in the period 2004-2011. Several variables were investigated for their relation with surgical outcome. RESULTS: A colovesical (n = 35) or colovaginal (n = 5) fistula was diagnosed in 18 men and 22 women. The mean age was 69 years (range, 45-90). A rectosigmoid resection with primary anastomosis was performed in 32 patients. Fourteen patients received a defunctioning ileostomy. Eight patients were treated with a Hartmann procedure. Overall 30-day treatmentrelated morbidity and mortality was 48 and 8 %, respectively. Major morbidity, because of anastomotic leakage, was mainly observed in the primary anastomosis group without a defunctioning ileostomy. Morbidity and mortality were associated with high body mass index, diabetes, use of corticosteroids, and American Society of Anesthesiologists classification, though not significantly. CONCLUSIONS: One should be liberal in the use of a defunctioning ileostomy in case of a primary anastomosis after colonic resection for a diverticular fistula, in order to prevent high morbidity rates due to anastomotic leakage. PMID: 22653331 [PubMed - in process]

Predictors of functional outcome following femoral neck fractures treated with an arthroplasty: limitations of the Harris hip score. Reuling EM, Sierevelt IN, van den Bekerom MP, Hilverdink EF, Schnater JM, van Dijk CN, Goslings JC, Raaymakers EL. Arch Orthop Trauma Surg. 2012 Feb;132(2):249-56. Epub 2011 Nov 24. INTRODUCTION: To study the association between potential prognostic factors and functional outcome at 1 and 5 year follow-up in patients with femoral neck fractures treated with an arthroplasty. To analyze the reliability of the Harris hip score (HHS). MATERIALS AND METHODS: A multicenter analysis which included 252 patients who sustained a femoral neck fracture treated with an arthroplasty. Functional outcome after surgery was assessed using a modified HHS and was evaluated after 1 (HHS1) and 5 (HHS5) years. Several prognostic factors were analyzed and reliability of the HHS was assessed. RESULTS: After 1 year the presence of co-morbidities was a significant (p = 0.002) predictor for a poor functional outcome (mean HHS1 71.8 with co-morbidities, and 80.6 without co-morbidities). After 5 years none of the potential prognostic factors had significant influence on functional outcome. Internal consistency testing of the HHS showed that when pain and function of the HHS were analyzed together, the internal consistency was poor (HHS1 0.38 and HHS5 0.20). The internal consistency of the HHS solely in function (without pain)improved to 0.68 (HHS1) and 0.46 (HHS5). Analyzing the functional aspect exclusively, age and the existence of co-morbidities could be defined as predictors for functional outcome of femoral neck fractures after 1 and 5 years. CONCLUSION: After using the HHS in a modification, age and the existence of pre-operative co-morbidities appeared to be predictors of the functional outcome after 1 and 5 years. The HHS, omitting pain, is a more reliable score to estimate the functional outcome, than HHS analyzing pain and function in one scoring system. PMCID: PMC3261383 PMID: 22113433 [PubMed - indexed for MEDLINE]

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Efficacy of Cognitive Behavioral Therapy and Physical Exercise in Alleviating Treatment-Induced Menopausal Symptoms in Patients With Breast Cancer: Results of a Randomized, Controlled, Multicenter Trial. Duijts SF, van Beurden M, Oldenburg HS, Hunter MS, Kieffer JM, Stuiver MM, Gerritsma MA, Menke-Pluymers MB, Plaisier PW, Rijna H, Lopes Cardozo AM, Timmers G, van der Meij S, van der Veen H, Bijker N, de Widt-Levert LM, Geenen MM, Heuff G, van Dulken EJ, Boven E, Aaronson NK. J Clin Oncol. 2012 Nov 20;30(33):4124-33. Epub 2012 Oct 8. PURPOSE: The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause. PATIENTS AND METHODS Patients with breast cancer reporting treatment-induced menopausal symptoms (N = 422) were randomly assigned to CBT (n = 109), PE (n = 104), CBT/PE (n = 106), or to a waiting list control group (n = 103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time. RESULTS Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P < .001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P = .002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P = .002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P < .001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P = .027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups. CONCLUSION CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence. PMID: 23045575 [PubMed - as supplied by publisher]

Humeral shaft fractures: Retrospective results of non-operative and operative treatment of 186 patients. Mahabier KC, Vogels LM, Punt BJ, Roukema GR, Patka P, Van Lieshout EM. Injury. 2012 Aug 28. [Epub ahead of print] BACKGROUND: Humeral shaft fractures account for 1-3% of all fractures and 20% of the fractures involving the humerus. The aim of the current study was to compare the outcome after operative and non-operative treatment of humeral shaft fractures, by comparing the time to radiological union and the rates of delayed union and complications. METHODS: All patients aged 16years or over treated for a humeral shaft fracture during a 5-year period were included in this retrospective analysis; periprosthetic and pathological fractures were excluded. Radiographs and medical charts were retrieved and reviewed in

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order to collect data on fracture classification, time to radiographic consolidation and the occurrence of adverse events. RESULTS: A total of 186 patients were included; 91 were treated non-operatively and 95 were treated operatively. Mean age was 58.7±1.5years and 57.0% were female. In 83.3% of the patients, only the humerus was affected. A fall from standing height was the most common cause of the fracture (72.0%). Consolidation time varied from a median of 11-28weeks. The rate of radial nerve palsy in both groups was similar: 8.8% versus 9.5%. In 5.3% of the operatively treated patients, the palsy resulted from the operation. Likewise, delayed union rates were similar in both groups: 18.7% following non-operative treatment versus 18.9% following surgery. CONCLUSION: The data indicated that consolidation time and complication rates were similar after operative and non-operative treatment. A prospective randomised clinical trial comparing non-operative with operative treatment is needed in order to examine other aspects of outcome, meaning shoulder and elbow function, postoperative infection rates, trauma-related quality of life and patient satisfaction. PMID: 22938959 [PubMed - as supplied by publisher]

Efficacy of cognitive behavioral therapy and physical exercise in alleviating treatment-induced menopausal symptoms in patients with breast cancer: results of a randomized, controlled, multicenter trial. Duijts SF, van Beurden M, Oldenburg HS, Hunter MS, Kieffer JM, Stuiver MM, Gerritsma MA, Menke-Pluymers MB, Plaisier PW, Rijna H, Lopes Cardozo AM, Timmers G, van der Meij S, van der Veen H, Bijker N, de Widt-Levert LM, Geenen MM, Heuff G, van Dulken EJ, Boven E, Aaronson NK. J Clin Oncol. 2012 Nov 20;30(33):4124-33. Epub 2012 Oct 8. PURPOSE: The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause. PATIENTS AND METHODS: Patients with breast cancer reporting treatment-induced menopausal symptoms (N=422) were randomly assigned to CBT (n=109), PE (n=104), CBT/ PE (n=106), or to a waiting list control group (n=103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time. RESULTS: Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P<.001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P=.002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P=.002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P<.001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P=.027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups.

26

CONCLUSION: CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence. PMID: 23045575 [PubMed - indexed for MEDLINE]

Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences. Kwast AB, Groothuis-Oudshoorn KC, Grandjean I, Ho VK, Voogd AC, Menke-Pluymers MB, van der Sangen MJ, Tjan-Heijnen VC, Kiemeney LA, Siesling S. Breast Cancer Res Treat. 2012 Aug;135(1):271-80. Epub 2012 Jul 19. Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR- subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER-PR- patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78-1.06, >3 years HR 1.07, 95 % CI 0.88-1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences. PMID: 22810087 [PubMed - indexed for MEDLINE]

Pubmed collaborative authorship publicaties Initial microbial spectrum in severe secondary peritonitis and relevence for treatment. Van Ruler O, Kiewiet JJ, van Ketel JJ, Boermeester MA; Dutch Peritonitis Study Group Collaborator: ...Lamme B… Eur J Clin Microbiol Infect Dis 2012; 31:671-82.

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Chirurgie

Overige publicaties Comparison of 30-day, 90-day and in hospital mortality in lung cancer surgery. Plaisier PW, Damhuis R. Interact Cardiovasc Thorac Surg 2012;15(suppl 1):S34.

Operative treatment of displaced midshaft clavicular fracture: is it the best treatment? van der Woude P, van der Vlies CH, Coenen JMFH, Vegt PA, Punt BJ. Current Orthopaedic Practice 2012, 23 (2).

Hip fracture surgery and performance indicators: an analysis of 941 patients operated in a large teaching hospital. Jakma TSC, Vijfhuize S, Vegt PA, Plaisier PW, Oostenbroek RJ, Punt BJ. Eur J Trauma Emerg Surg February 2012, 38(1): 49-52.

Comparable results for transverse colectomy and extended hemicolectomy in case of cancer of the transverse colon. Plaisier PW, van Rongen I, van der Hoeven JAB, Damhuis RAM. Eur J Surg Oncol 2012; 38: 826.

Interim analysis of systemic incident reconstruction ans evaluations of adverse events after surgery for lung cancer in the Rotterdam area. Plaisier PW, Maat APWM, de Rooij PD, et al. Eur J Surg Oncol 2012; 38: 861.

Wat zijn de klachten van patiënten over de AIOS en welke kosten brengt dit met zich mee? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. Congres Nederlandse Vereniging voor Medisch Onderwijs, Maastricht, november 2012.

Hoe kan de medische staf in algemene ziekenhuizen bij opleiden betrokken worden? Van de Ridder JMM, Oostenbroek RJ, Verheijen FM, Zanting A, Plaisier PW. Congres Nederlandse Vereniging voor Medisch Onderwijs, Maastricht, november 2012.

Consult online: digitaal advies voor tropenartsen. Baerends EP, Reuling EMBP, Bijen CBM. Ned Tijdschr Geneeskd 2012;156:A5566.

Voordrachten Hip to revise? Punt BJ. Patient Care symposium Canada.

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Missed fractures in the Multi Trauma Patient. Punt BJ, Caldwell E, DÁmours S, Sugrue M. Patient Care symposium Canada.

Sentinel node identification rate and further nodal involvement in patient with multifocal breast cancer in the EORTC 10981-22023 AMAROS trial. Donker M. 8ste European Breast Cancer Conference, Wenen, 21-24 april 2012.

Adjuvant radiotherapy after breast-conserving surgery for ductal carcinoma-in-situ: fifteen-year results of the European Organisation for Research and Treatment of Cancer randomised phase III trial 10853. Donker M. 8ste European Breast Cancer Conference, Wenen, 21-24 april 2012.

Resultaten van de SWK-procedure in patiënten met een multifocaal mammacarcinoom in de EORTC 10981-22023 AMAROS studie. Donker M. Chirurgendagen, Veldhoven, 10-11 mei 2012. Geaccrediteerd door Nederlandse Vereniging voor Heelkunde.

Adjuvante radiotherapie na mamma-sparende chirurgie voor ductal carcinoom-in-situ: vijftien-jaars resultaten van een gerandomiseerde EORTC fase III studie. Donker M. Chirurgendagen, Veldhoven, 10-11 mei 2012.

Patiënten <35 jaar: sparend of ablatief opereren? Menke MBE. 10e Bossche Mamma congres, Vught, 19 juni 2012. Geaccrediteerd door Nederlandse Vereniging voor Heelkunde.

I-aid studie, zorgtraject voor een betere kwaliteit van zorg en leven voor stomapatiënten. Sier MF. Stoma in ontwikkeling symposium, Amsterdam, 11 april 2012.

Validation of duplex ultrasound vascular flow parameters. Hoedt MTC, Toonder IM, How TV, Wittens CHA. ESVS congres, Bologna Italië, 18-21 september 2012.

Haemodynamic flow patterns in 3D anatomical shaped end-to-end and end-to-side anastomoses in femoropopliteal bypass: in vitro flow visualisation. Hoedt MTC, How TV, Poyck PPC, Wittens CHA. ESVS congres, Bologna Italië, 18-21 september 2012.

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Chirurgie

3D CT movement analysis as a new tool in diagnosing femoroacetabular impingement in young athletes. Röling MA. European Hip Society Congres, Milaan. 20-22 september 2012.

Residents prefer to evaluate the Educational Climate more often than supervisors consider this necessary. Plaisier PW. Meeting of the Association for Medical Education in Europe, Lyon Frankrijk, augustus 2012. Geaccrediteerd door Association for Medical Education in Europe.

Is the formative assessment process for surgical residents reliable? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. 15th Ottawa Conference on Assessment of Competence in Medicine and the Healthcare Professions, Maart 2012, Kuala Lumpur, Maleisië. Geaccrediteerd door Ottawa Conference on Assessment of Competence in Medicine and the Healthcare Professions.

Outcome of surgery for colovesical and colovaginal fistula of diverticular origin in 40 patients. Smeenk RM, Plaisier PW, van der Hoeven JAB, Hesp WLEM. Biannial World Conference of the International College of Surgeons, Brisbane Australië, November 2012. Geaccrediteerd door International College of Surgeons.

Audits in de longchirurgie (ervaringen in de regio Rotterdam). Plaisier PW. Werkgroep Longtumoren IKNL, Leiden, november 2012.

Wat zijn de klachten van patiënten over AIOS en welke kosten brengt dit met zich mee? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. 40e NVMO congres, November 2012, Maastricht. Geaccrediteerd door Nederlandse Vereniging voor Medisch Onderwijs.

Evalueren van het leerklimaat: hoe vaak eigenlijk? Oostenbroek RJ, Plaisier PW, van de Ridder JMM mede namens het AAV-bestuur. 40e NVMO congres, November 2012, Maastricht. Geaccrediteerd door Nederlandse Vereniging voor Medisch Onderwijs.

Hoe kan de medische staf in algemene ziekenhuizen bij opleiden betrokken worden? van de Ridder JMM, van Bommel EFH, Koopman-van Gemert AWMM, Oostenbroek RJ, Verheijen FM, van Zanting A, Plaisier PW. 40e NVMO congres, November 2012, Maastricht. Geaccrediteerd door Nederlandse Vereniging voor Medisch Onderwijs.

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Posters Fertility in Men with Acquired Undescended Testis: Spontaneous Descend versus Orchiopexy at Puberty. Brakel J. 27ste European Association of Urology congres, Parijs, 24-28 februari 2012.

Results of three years hip arthroscopy: a promising technique for intra-articular pain of the hip in young patients. Röling MA. European Hip Society Congres, Milaan. 20-22 september 2012.

Outcome of surgery for colovesical and colovaginal fistula of diverticular origin in 40 patients. Smeenk RM, Plaisier PW, van der Hoeven JAB, Hesp WLEM. United European Gastroenterology Week 2012, Amsterdam, oktober 2012.

Residents’ perception of assessment and feedback in a surgical department: supervisors must do better! Plaisier PW, Oostenbroek RJ, van de Ridder JMM. 15th Ottawa Conference on Assessment of Competence in Medicine and the Healthcare Professions, Maart 2012, Kuala Lumpur, Maleisië.

What are patients’ complaints about residents and what are the costs? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. 2012 Meeting of the Association for Medical Education in Europe, Augustus 2012, Lyon, Frankrijk.

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Chirurgie

Dermatologie

PubMed publicaties Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein. Shadid N, Ceulen R, Nelemans P, Dirksen C, Veraart J, Schurink GW, van Neer P, Vd Kley J, de Haan E, Sommer A. Br J Surg. 2012 Aug;99(8):1062-70. BACKGROUND: New minimally invasive treatment modalities, such as ultrasound-guided foam sclerotherapy (UGFS), are becoming more popular. In a multicentre randomized controlled non-inferiority trial, the effectiveness and costs of UGFS and surgery for treatment of the incompetent great saphenous vein (GSV) were compared. METHODS: Patients with primary great saphenous varicose veins were assigned randomly to either UGFS or surgical stripping with high ligation. Recurrence, defined as reflux combined with venous symptoms, was determined on colour duplex scans at baseline, 3 months, 1 year and 2 years after initial treatment. Secondary outcomes were presence of recurrent reflux (irrespective of symptoms), reduction of symptoms, health-related quality of life (EQ-5D(™) ), adverse events and direct hospital costs. RESULTS: Two hundred and thirty patients were treated by UGFS and 200 underwent GSV stripping. The 2-year probability of recurrence was similar in the UGFS and surgery groups: 11·3 per cent (24 of 213) and 9·0 per cent (16 of 177) respectively (P = 0·407). At 2 years, reflux irrespective of venous symptoms was significantly more frequent in the UGFS group (35·0 per cent) than in the surgery group (21·0 per cent) (P = 0·003). Mean(s.d.) hospital costs per patient over 2 years were €774(344) per patient for UGFS and €1824(141) for stripping. CONCLUSION: At 2-year follow-up, UGFS was not inferior to surgery when reflux associated with venous symptoms was the clinical outcome of interest. UGFS has the potential to be a cost-effective approach to a common health problem. PMID: 22627969 [PubMed - in process]

Enteric-coated mycophenolate sodium in psoriasis vulgaris: an open pilot study. Fallah Arani S, Waalboer Spuij R, Nijsten T, Neumann HA, Thio B. J Dermatolog Treat. 2012 Sep 24. [Epub ahead of print] BACKGROUND: Mycophenolate mofetil is a well known immunosuppressive agent in transplantation medicine. The efficacy of enteric-coated mycophenolate sodium (EC-MPS) was confirmed in other inflammatory skin diseases, including atopic dermatitis and SCLE. OBJECTIVE: To investigate the efficacy and the tolerability/short term safety of EC-MPS in patients with moderate to severe chronic plaque psoriasis. Patients and methods: An open label pilot study in which 20 patients with a PASI>10 received EC-MPS 720 mg twice daily for 6 weeks followed by 360 mg twice daily for another 6 weeks. Patients who completed 12-weeks of treatment were followed up for an additional 12 weeks. Treatment outcomes were assessed with PASI50% and PASI75%.

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RESULTS: 18 males and 2 females (mean age 46 years) entered the study. 65% (13/20) finished the treatment period. In week 6, no patient achieved PASI75% and 8/20 patients achieved a PASI50%. Compared to week 6, 4/13 showed a deterioration of their psoriasis at week 12. 25% (2/8), achieved a PASI 75% in week 24. The most reported adverse events were itching (30%), diarrhea (10%) and a reversible elevation of the triglycerides level. CONCLUSION: EC-MPS does not seem effective as monotherapy for moderate to severe psoriasis, but might be used at a dosage of 1440mg daily in well-selected patients with treatment resistant psoriasis. PMID: 22998609 [PubMed - as supplied by publisher]

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Dermatologie

Facilitair bedrijf

Overige publicaties Sturen op een gastvrij zorggebouw. Het creëren van een healing environment. Prevosth J, van der Voordt T en Doets M. Facility Management Magazine | Jaarboek 2013 | 26- 27.

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PubMed publicaties Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial. van der Ham DP, Vijgen SM, Nijhuis JG, van Beek JJ, Opmeer BC, Mulder AL, Moonen R, Groenewout M, van Pampus MG, Mantel GD, Bloemenkamp KW, van Wijngaarden WJ, Sikkema M, Haak MC, Pernet PJ, Porath M, Molkenboer JF, Kuppens S, Kwee A, Kars ME, Woiski M, Weinans MJ, Wildschut HI, Akerboom BMC, Mol BW, Willekes C; PPROMEXIL trial group. PLoS Med. 2012 Apr;9(4):e1001208. Epub 2012 Apr 24. BACKGROUND: At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term. METHODS AND FINDINGS: We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34(+0) and 37(+0) wk of gestation. Participants were randomly allocated in a 1∶1 ratio to induction of labor (IoL) or expectant management (EM)using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate. From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported. Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM. CONCLUSIONS: In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29313500 PMCID: PMC3335867 PMID: 22545024 [PubMed - in process]

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Gynaecologie

Management of late-preterm premature rupture of membranes: the PPROMEXIL-2 trial. van der Ham DP, van der Heyden JL, Opmeer BC, Mulder ALM, Moonen RMJ, van Beek JHJ, Franssen MTM, Bloemenkamp KWM, Sikkema JMM, de Groot CJM, Porath M, Kwee A, Woiski MD, Duvekot JHJ, Akerboom BMC, van Loon AJ, de Leeuw JW, Willekes C, Mol BWJ, Nijhuis JG. American Journal of Obstetrics and Gynecology 2012. Accepted for publication.

Risk of developmental dysplasia of the hip in breech presentation: the effect of successful external cephalic version. Lambeek A, De Hundt M, Vlemmix F, Akerboom BMC, Bais J, Papatsonis D, Mol B, Kok M. BJOG. 2012 Nov 12. [Epub ahead of print] OBJECTIVE: To evaluate the effect of successful external cephalic version on the incidence of developmental dysplasia of the hip (DDH) requiring treatment in singleton breech presentation at term. Design Observational cohort study. Setting Three large teaching hospitals in the Netherlands. Population Women with a singleton breech presentation of 34 weeks of gestation or more, who underwent an external cephalic version attempt. METHODS: We made a comparison of the incidence of DDH between children born in breech presentation and children born in cephalic presentation after a successful external cephalic version. Main outcome measure The incidence of DDH requiring either conservative treatment, with a harness, or surgical treatment. RESULTS: A total of 498 newborns were included in the study, of which 40 (8%) were diagnosed with DDH and 35 required treatment. Multivariate analysis showed that female gender (OR 2.79, 95% CI 1.23–6.35) and successful external cephalic version (OR 0.29, 95% CI 0.09–0.95) were independently associated with DDH. CONCLUSIONS: A successful external cephalic version is associated with a lower incidence of DDH, although a high percentage of children born after a successful external cephalic version still appear to have DDH. A larger cohort study is needed to establish the definite nature of this relationship. Until then, we recommend the same screening policy for infants born in cephalic position after a successful external cephalic version as for infants born in breech position. PMID: 23145903 [PubMed - as supplied by publisher]

Bladder polyps following Avaulta anterior mesh vaginal wall repair. Auzin M, Teune TM, Hogewoning CJ. Int Urogynecol J. 2012 Apr 25. [Epub ahead of print] We present the case of a postmenopausal woman who developed bladder polyps leading to serious abdominal pain, dysuria with mucus and blood, and urinary incontinence after anterior vaginal wall repair using Avaulta anterior mesh(Bard®). All of these symptoms resolved after mesh removal. This case emphasizes that not all complications of mesh are known. PMID: 22531953 [PubMed - as supplied by publisher]

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Brush-based self-sampling in combination with GP5+/6+-PCR-based hrHPV testing: high concordance with physician-taken cervical scrapes for HPV genotyping and detection of high-grade CIN. Dijkstra MG, Heideman DA, van Kemenade FJ, Hogewoning CJ, Hesselink AT, Verkuijten MC, van Baal WM, Boer GM, Snijders PJ, Meijer CJ. J Clin Virol. 2012 Jun;54(2):147-51. Epub 2012 Mar 23. BACKGROUND: Studies have shown that self-sampling for hrHPV testing (HPV self-sampling) is highly acceptable to women, increases screening participation rate, and may therefore further reduce cervical cancer incidence. However, it is important to clinically validate HPV self-sampling procedures for screening purposes. OBJECTIVES: Clinical validation of combined brush-based self-sampling with GP5+/6+-PCR EIA for primary cervical screening. In addition, HPV type-specific agreement between sample types and acceptability of brush-based self-sampling were evaluated. STUDY DESIGN: 135 women referred for colposcopy took a self-sample at home prior to vaginal- and cervical sampling by a gynaecologist. All women were biopsied for histology. HPV testing was done by GP5+/6+-PCR EIA, with genotyping by reverse line blotting (RLB). Acceptability of sampling methods was measured with a questionnaire. RESULTS: In this outpatient population, hrHPV test results showed good concordance between self-samples and physician-taken cervical scrapes (86%, k=0.70), with sensitivities and specificities for CIN2+ that did not differ significantly (93% and 51%, 91% and 51%, respectively (P=1.0)). The clinical sensitivity of brush-based self-sampling combined with GP5+/6+-PCR EIA hrHPV testing for detection of CIN2+ was non-inferior to that of hrHPV testing on physician-taken cervical samples (P=0.018). In addition, hrHPV genotyping results were highly concordant between sample types, with almost perfect agreement for HPV16 (k=0.81) and HPV18 (k=0.92). Finally, 91% of participants described brush-based self-sampling as easy-to-use. CONCLUSIONS: Brush-based self-sampling in combination with GP5+/6+-PCR EIA hrHPV testing is acceptable to women and valid for assessing the risk of CIN2+ in comparison to hrHPV testing on physician-taken scrapes. In addition, there was high concordance of HPV genotyping results. Therefore, this HPV self-sampling procedure may be considered for use in routine cervical screening. PMID: 22445557 [PubMed - in process]

The MiniArc sling for female stress urinary incontinence: clinical results after 1-year follow-up. Hogewoning CR, Ruhe IM, Bekker MD, Hogewoning CJ, Putter H, DeRuiter MC, Pelger RC, Elzevier HW. Int Urogynecol J. 2012 May;23(5):589-95. Epub 2011 Nov 23. INTRODUCTION AND HYPOTHESIS: The objective of this study was the assessment of the efficiency of the MiniArc for curing stress urinary incontinence. METHODS: Seventy-seven patients, operated on from March 2008 to November 2009, were evaluated in this study. One-year post-operative data are presented. All patients suffered from predominant stress urinary incontinence. After 1 year, response was 74%. Evaluation was performed using a questionnaire consisting of the EuroQol-5 Dimensions, the Patient Global Impression of Improvement, the Incontinence Impact Questionnaire, the Urinary

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Gynaecologie

Distress Inventory, the Prolapse/Urinary Incontinence Sexual Questionnaire, short form, and the Defecation Distress Inventory. RESULTS: One year after surgery, 68% of the patients stated an improvement in their incontinence status, while only 44% stated to be completely dry. CONCLUSION: The 1-year follow-up suggests that the MiniArc is less effective in the treatment of stress urinary incontinence than the TVT. PMCID: PMC3332378 PMID: 22109702 [PubMed - indexed for MEDLINE]

Male circumcision is associated with a lower prevalence of human papillomavirus-associated penile lesions among Kenyan men. Backes DM, Bleeker MC, Meijer CJ, Hudgens MG, Agot K, Bailey RC, Ndinya-Achola JO, Hayombe J, Hogewoning CJ, Moses S, Snijders PJ, Smith JS. Int J Cancer. 2012 Apr 15;130(8):1888-97. Epub 2011 Aug 2. Human papillomavirus (HPV)-associated penile lesions in men may increase the risk of HPV transmission to their female partners. Risk factor data on HPV-associated penile lesions are needed from regions with a high burden of cervical cancer. Visual inspection of the penis was conducted using a colposcope at the 24-month visit among participants in a randomized controlled trial of male circumcision in Kenya, from May 2006 to October 2007. All photos were read independently by two observers for quality control. Penile exfoliated cells sampled from the glans/coronal sulcus and the shaft were tested for HPV DNA using GP5+/6+ PCR and for HPV16, 18 and 31 viral loads using a real time PCR assay. Of 275 men, 151 were circumcised and 124 uncircumcised. The median age was 22 years. Circumcised men had a lower prevalence of flat penile lesions (0.7%) versus uncircumcised (26.0%); adjusted odds ratio (OR) = 0.02; 95% confidence interval (CI) = 0.003-0.1. Compared to men who were HPV negative, men who were HPV DNA positive (OR = 6.5; 95% CI = 2.4-17.5) or who had high HPV16/18/31 viral load (OR = 5.2; 95% CI = 1.1-24.4) had higher odds of flat penile lesions. Among men with flat penile lesions, HPV56 (29.0%) and 16 (25.8%) were the most common types within single or multiple infections. Flat penile lesions are much more frequent in uncircumcised men and associated with higher prevalence of HPV and higher viral loads. This study suggests that circumcision reduces the prevalence of HPV-associated flat lesions and may ultimately reduce male-to-female HPV transmission. PMCID: PMC3262059 [Available on 2013/4/15] PMID: 21618520 [PubMed - indexed for MEDLINE]

Induction of delivery by mifepristone and misoprostol in termination of pregnancy and intrauterine fetal death: 2nd and 3rd trimester induction of labour. Stibbe KJ, de Weerd S. Arch Gynecol Obstet Sep;286 (3):795-6. No abstract available. PMID: 22434057 [PubMed - as supplied by publisher]

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The capacity of endometrial thickness measurement to diagnose endometrial carcinoma in asymptomatic postmenopausal women: a systematic review and meta analysis. Breijer MC, Peeters JA, Opmeer BC, Justin Clark T, Verheijen RH, Mol BW, Timmermans A. Ultrasound Obstet Gynecol. 2012 Sep 24. OBJECTIVES: Measurement of endometrial thickness is an important tool in the assessment of women with postmenopausal bleeding. The place of endometrial thickness measurement by ultrasound in asymptomatic women is unclear. The aims of this study were to address: (I) the normal endometrial thickness measured with ultrasonography, (II) the prevalence of serious endometrial pathology and (III) the sensitivity and specificity of endometrial thickness measurement by transvaginal ultrasonography (TVS) for diagnosing premalignant and malignant endometrial disease in asymptomatic postmenopausal women. METHODS: A Medline and Embase search (from inception to January 2011) was performed. Articles reporting on endometrial thickness measurement in the diagnosis of endometrial carcinoma and atypical hyperplasia in asymptomatic postmenopausal women without HRT were selected. Endometrial thickness and the prevalence of endometrial (pre-)malignancies were recorded. If possible, 2x2 tables were extracted. RESULTS: We included 32 studies reporting on 11,100 women to answer our three objectives: (I) The estimated mean endometrial thickness was 2.9 mm (95% CI 2.6 to 3.3). (II) The pooled estimated prevalence of endometrial carcinoma and atypical endometrial hyperplasia were 0.62% (95% CI 0.42 to 0.82), and 0.59% (95% CI 0.22 to 0.96), respectively. (III) Summary estimates for sensitivity and specificity of TVS endometrial thickness measurement were 0.83 (95% CI 0.19 to 1.00) and 0.72 (95% CI 0.32 to 0.93) for 5 mm cut-off and 0.33 (95% CI 0.04 to 0.85) and 0.94 (95% CI 0.92 to 0.96) for 6 mm cut-off. CONCLUSIONS: The results from this review do not justify further diagnostic investigation on basis of endometrial thickness measurement only in asymptomatic postmenopausal women without HRT. PMID: 23001905 [PubMed - as supplied by publisher]

Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years. Leenen CH, van Lier MG, van Doorn HC, van Leerdam ME, Kooi GS, de Waard J, Hoedemaeker RF, van den Ouweland AM, Hulspas SM, Dubbink HJ, Kuipers EJ, Wagner A, Dinjens WN, Steyerberg EW. Gynecol Oncol. 2012 May;125(2):414-20. Epub 2012 Feb 1. OBJECTIVE: Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients ≤ 70 years. METHODS: Consecutive EC patients ≤ 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS).

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Gynaecologie

RESULTS: Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified. CONCLUSIONS: Molecular screening for LS in patients with EC diagnosed ≤ 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age. PMID: 22306203 [PubMed - indexed for MEDLINE]

Overige publicaties Het effect van de Pelvilace® collageen sling na eerdere complicaties van een incontinentie ingreep. Hogewoning CRC, Hogewoning CJA, Elzevier HW, Pelger H. Ned tijdschrift voor Urologie.

Voordrachten Homocysteine Affects Early Heart Function in the Chicken Embryo Oosterbaan AM. 9e Symposium Wim Schellekens Stichting, 8 juni 2012, Westeinde Ziekenhuis Den Haag, prijs beste junior spreker.

ICS Physiotherapists-what do they do? Experiences of the gynaecologist pre-congres meeting. Hogewoning CJ. 42nd Annual Meeting of the ICS, 10 october, Beijing China.

Posters Assessment of External Cephalic Version in a Dutch Regional Hospital. Cabenda-Narain N. FIGO International Federation of Gynecology and Obstetrics congres, Rome Italie, 7-12 October 2012.

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Interne geneeskunde

PubMed publicaties Clinical research: benefits of Bhattacharya modeling. Solis MC, Cleophas TJ. Int J Clin Pharmacol Ther. 2012 Feb;50(2):129-35. BACKGROUND: Bhattacharya modeling is a Gaussian method recommended by the Food and Agricultural Organization of the United Nations Guidelines for analyzing the eco-system. It is rarely used in clinical research. OBJECTIVE: To investigate the performance of Bhattacharya modeling for clinical data analysis. METHODS: Using as examples simulated vascular lab scores we assessed the performance of the Bhattacharya method. SPSS statistical software is used. RESULTS: 1. The Bhattacharya method better fitted the data from a single sample than did the usual Gaussian curve derived from the mean and standard deviation with 15 vs. 9 cuts. 2. Bhattacharya models demonstrated a significant difference at p < 0.0001 between the data from two parallel-groups, while the usual t-test and Mann-Whitney test were insignificant at p = 0.051 and 0.085. 3. Bhattacharya modeling of a histogram suggestive of certain subsets identified three Gaussian curves. CONCLUSIONS: We recommend that Bhattacharya modeling be more often considered in clinical research for the purpose of (1) unmasking normal values of diagnostic tests, (2) improving the p-values of data testing and (3) objectively searching subsets in the data. PMID: 22257578 [PubMed - indexed for MEDLINE]

Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype. van der Weerd K, Dik WA, Schrijver B, Schweitzer DH, Langerak AW, Drexhage HA, Kiewiet RM, van Aken MO, van Huisstede A, van Dongen JJ, van der Lelij AJ, Staal FJ, van Hagen PM. Diabetes. 2012 Feb;61(2):401-8. Epub 2012 Jan 6. Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+ T-cell numbers

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Interne geneeskunde

correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point. PMCID: PMC3266399 [Available on 2013/2/1] PMID: 22228716 [PubMed - indexed for MEDLINE]

A Hospital-Based Work Support Intervention to Enhance the Return to Work of Cancer Patients: A Process Evaluation. Tamminga SJ, de Boer AG, Bos MM, Fons G, Kitzen JJ, Plaisier PW, Verbeek JH, Frings-Dresen MH. J Occup Rehabil. 2012 Jun 15. [Epub ahead of print] PURPOSE: To perform a process evaluation of a hospital-based work support intervention for cancer patients aimed at enhancing return to work and quality of life. The intervention involves the delivery of patient education and support at the hospital and involves the improvement of the communication between the treating physician and the occupational physician. In addition, the research team asked patient’s occupational physician to organise a meeting with the patient and the supervisor to make a concrete gradual return-to-work plan. METHODS: Eligible were cancer patients treated with curative intent and who have paid work. Data were collected from patients assigned to the intervention group (N = 65) and from nurses who delivered the patient education and support at the hospital (N = 4) by means of questionnaires, nurses’ reports, and checklists. Data were quantitatively and qualitatively analysed. RESULTS: A total of 47 % of all eligible patients participated. Nurses delivered the patient education and support in 85 % of the cases according to the protocol. In 100 % of the cases at least one letter was sent to the occupational physician. In 10 % of the cases the meeting with the patient, the occupational physician and the supervisor took place. Patients found the intervention in general very useful and nurses foundthe intervention feasible to deliver. CONCLUSIONS: We found that a hospital- based work support intervention was easily accepted in usual psycho-oncological care but that it proved difficult to involve the occupational physician. Patients were highly satisfied and nurses found the intervention feasible. PMID: 22699884 [PubMed - as supplied by publisher]

Fibrosing pericarditis in a patient with encapsulating peritoneal sclerosis. Tonneijck L, Florquin S, Korte MR, Schut NH. Perit Dial Int. 2012 Nov;32(6):660-2. PMID: 23212862 [PubMed - in process]

Value of acute-phase reactants in monitoring disease activity and treatment response in idiopathic retroperitoneal fibrosis. Pelkmans LG, Aarnoudse AJ, Hendriksz TR, van Bommel EFH. Nephrol Dial Transplant. 2012 Jul;27(7):2819-25. Epub 2012 Jan 23. BACKGROUND: Prospective evaluation of the value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in monitoring disease activity and treatment response in patients with idiopathic retroperitoneal fibrosis (RPF). 42

METHODS: This study included 57 patients with idiopathic RPF receiving tamoxifen monotherapy with at least 8 months follow-up. Clinical, laboratory and radiological investigation was performed at presentation and at repeated follow-up. Remission was defined as significant clinical improvement within 6 weeks of treatment together with stable or decreasing mass size on follow-up computed tomography (CT) scanning at 4 months and definitive decrease in mass size on follow-up CT scanning at 8 months. RESULTS: ESR and CRP levels at presentation and their respective decreases over time correlated strongly with each other (P < 0.001). Baseline ESR and CRP levels correlated with visual analogue scale (VAS) score for pain (ESR, P < 0.01; CRP, P < 0.001); baseline ESR levels also correlated with VAS score for discomfort (P < 0.001). Short-term decreases in ESR or CRP levels at 6 weeks follow-up did not correlate with subsequent mass regression but decrease in ESR at 4 months and decrease in CRP at 4 and 8 months follow-up correlated with mass regression. Kaplan-Meier analysis showed no difference in remission rate between patients with normal or elevated baseline ESR or CRP (log-rank P = 0.22/P = 0.88) or between patients with or without (near-)normalization of ESR or CRP in first 6 weeks of treatment (logrank P = 0.12/P = 0.32). CONCLUSIONS: Patients with idiopathic RPF who have elevated acute-phase reactant levels are more symptomatic. Neither acute-phase reactant levels or their initial changes can be taken as a major predictor for treatment success. PMID: 22273666 [PubMed - in process]

Potassium treatment for hypertension in patients with high salt intake: a meta-analysis. van Bommel EFH, Cleophas TJ. Int J Clin Pharmacol Ther. 2012 Jul;50(7):478-82. BACKGROUND: Previous metaanalyses of potassium supplementation in patients with hypertension observed little or no benefit, but failed to account the amount of salt intake. OBJECTIVE: To assess the effect on blood pressure of potassium treatment in patients with high salt intake. METHODS: We meta-analyzed studies of patient populations with both high salt and potassium intake. We searched Medline, Google, major journals, Pubmed. Publication bias, lack of heterogeneity, and lack of robustness were assessed using standard procedures for such purposes. RESULTS: After the exclusion of 32 studies 10 studies were left in the meta-analysis. A pooled reduction of systolic blood pressure of -9.5 mmHg (95% confidence interval -10.8 to -8.1) and of diastolic blood pressure -6.4 mmHg (-7.3 to -5.6) was observed. These results were very heterogeneous (I2-values of 94 and 95%). After exclusion of single authored studies the results fell but remained statistically significant, -7.1 mmHg (-8.5 to -5.7), and -4.9 mmHg (-5.8 to -4.0). Heterogeneity of systolic blood pressure was no longer observed (I2-value 24.3%). Some publication bias was observed. CONCLUSIONS: 1. Potassium treatment reduces the blood pressure substantially in hypertensive patients with salt-rich diets. 2. The difference in magnitude of blood pressure reduction between different studies is probably related to the amount of salt intake. 3. Patients with reduced salt intake benefit little from potassium treatment. 4. Major meta-analyses published to date have severely underestimated the potential benefit of potassium treatment in patients with hypertension. PMID: 22541753 [PubMed - indexed for MEDLINE] 43

Interne geneeskunde

The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia. Castel R, Tax MG, Droogendijk J, Leers MP, Beukers R, Levin MD, Sonneveld P, Berendes PB. Clin Chem Lab Med. 2012 Feb 11;50(8):1343-9. BACKGROUND: Serum ferritin is the best single laboratory test to diagnose iron deficiency anemia (IDA). Ferritin levels <20 μg/L are highly specific for IDA, and ferritin levels >100 μg/L usually exclude IDA. However, ferritin concentrations between 20 and 100 μg/L are often inconclusive. The objective of this study was to improve the diagnosis of IDA when ferritin levels are inconclusive. METHODS: We evaluated the predictive performance of classic (ferritin, mean corpuscular volume, transferrin and serum iron) and modern [reticulocyte hemoglobin content, serum transferrin receptor and soluble transferrin receptor (sTfR)/log(ferr)] iron status parameters to diagnose IDA in 2084 anemic, non-hospitalized patients. The results were validated in an independent cohort of 274 anemic patients. RESULTS: In our study population, 29% (595 patients) of the patients had a ferritin level between 20 and 100 μg/L, hampering diagnosis of IDA. None of the classic or modern parameters was capable of completely separating the IDA population from the non-IDA population. However, using a new parameter, the transferrin/log(ferritin) ratio, the IDA and non-IDA populations can be completely separated. At a cut-off value of 1.70, the transferrin/ log(ferritin)ratio indicates IDA in 29% of the patients with inconclusive ferritin levels. CONCLUSIONS: The transferrin/log(ferritin) ratio is a practical new tool that improves diagnosis of iron deficiency when ferritin levels are inconclusive. PMID: 22868798 [PubMed - in process]

A fatal complication caused by occult pheochromocytoma after splenic artery embolization for malignant hypersplenism. Dinkelaar W, Elgersma O, Levin MD. Cardiovasc Intervent Radiol. 2012 Aug;35(4):971-4. PMCID: PMC3396346 PMID: 22190248 [PubMed - in process]

Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK). Ossenkoppele GJ, Stussi G, Maertens J, van Montfort K, Biemond BJ, Breems D, Ferrant A, Graux C, de Greef GE, Halkes CJ, Hoogendoorn M, Hollestein RM, Jongen-Lavrencic M, Levin MD, van de Loosdrecht AA, van Marwijk Kooij M, van Norden Y, Pabst T, Schouten HC, Vellenga E, Verhoef GE, de Weerdt O, Wijermans P, Passweg JR, Löwenberg B. Blood. 2012 Dec 6;120(24):4706-11. An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15. In the second cycle, patients received

44

cytarabine 1000 mg/m(2) twice daily on days 1-6 with or without bevacizumab. The complete remission rates in the 2 arms were not different (65%). Event-free survival at 12 months was 33% for the standard arm versus 30% for the bevacizumab arm; at 24 months, it was 22% and 16%, respectively (P = .42). The frequencies of severe adverse events (SAEs) were higher in the bevacizumab arm (n = 63) compared with the control arm (n = 28; P = .043), but the percentages of death or life-threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). The results of the present study show that the addition of bevacizumab to standard chemotherapy does not improve the therapeutic outcome of older AML patients. This trial is registered as number NTR904 in The Nederlands Trial Register (www.trialregister.nl). PMID: 23047822 [PubMed - in process]

Localized encapsulating peritoneal sclerosis constricting the terminal ileum; an unusual appearance requiring surgical intervention. Habib SM, Hagen SM, Korte MR, Zietse R, Dor FJMF, Betjes MGH. Perit Dial Int (in press).

Pubmed collaborative authorship publicaties Mortality after surgery in Europe: a 7 day cohort study. Pearse RM, Moreno RP, Bauer P, Pelosi P, Metnitz P, Spies C, Vallet B, Vincent L, Hoeft A, Rhodes A; European Surgical Outcomes Study (EuSOS) group for the rials groups of the European Society of Intensive Care Medicine and the European ociety of Anaesthesiology. Collaborators: …te Velde L…Ponssen H… BACKGROUND: Clinical outcomes after major surgery are poorly described at the ational level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe. METHODS: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ(2) and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries. FINDINGS: We included 46,539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9-3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0-3·0] for Iceland to 21·5% [16·9-26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19-1·05; p=0·06] for Finland to 6·92 [2·37-20·27; p=0·0004] for Poland).

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INTERPRETATION: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients. FUNDING: European Society of Intensive Care Medicine, European Society of Anaesthesiology. PMID: 22998715 [PubMed - in process]

Initial microbial spectrum in severe secondary peritonitis and relevance for treatment. van Ruler O, Kiewiet JJ, van Ketel RJ, Boermeester MA; Dutch Peritonitis Study Group. Collaborators: … te Velde L … Ponssen HH … This study aims to determine whether abdominal microbial profiles in early severe secondary peritonitis are associated with ongoing infection or death. The study is performed within a randomized study comparing two surgical treatment strategies in patients with severe secondary peritonitis (n = 229). The microbial profiles of cultures retrieved from initial emergency laparotomy were tested with logistic regression analysis for association with ‘ongoing infection needing relaparotomy’ and in-hospital death. No microbial profile or the presence of yeast or Pseudomonas spp. was related to the risk of ongoing infection needing relaparotomy. Resistance to empiric therapy for gram positive cocci and coliforms was moderately associated with ongoing abdominal infection (OR 3.43 95%CI 0.95-12.38 and OR 7.61, 95%CI 0.7576.94). Presence of only gram positive cocci, predominantly Enterococcus spp, was borderline independently associated with in-hospital death (OR 3.69, 95%CI 0.99-13.80). In secondary peritonitis microbial profiles do not predict ongoing abdominal infection after initial emergency laparotomy. However, the moderate association of ongoing infection with resistance to the empiric therapy compels to more attention for resistance when selecting empiric antibiotic coverage. PMCID: PMC3319890 PMID: 21800218 [PubMed - indexed for MEDLINE]

Overige publicaties Thrombolysis in a mechanically ventilated patient with haemodynamically stable acute pulmonary embolism and a patent formane ovale. Arends JJ. Netherlands Journal of Critical Care 2012: 16 (3) 97 - 100.

Rituximab-PECC Induction Followed by 90y-Ibritumomab Tiuxetan Consolidation in Relapsed or Refractory DLBCL Patients Who Are Not Eligible for or After ASCT: Preliminary Results From a Phase II HOVON Study. Lugtenburg PJ , Zijlstra JM, Doorduijn JK, Böhmer LH, Marwijk Kooy M, Hoogendoorn M, Berenschot HW, Beeker A, Valster FA, Schouten HC, Luten M, Chitu DA, Brouwer RE and van Imhoff GW. HOVON 85. ASH 2012.

Assessing seasonality in clinical research. Cleophas TJ, Zwinderman AH. Clin Chem Lab Med 2012; 50(12):2163-9 46

The Assessment of Non-Linear Effects in Clinical Research. Cleophas TJ, Zwinderman AH. Pharmacology & Pharmacy, 2012, 3, 139-147.

Encapsulating peritoneal sclerosis: een ingekapselde diagnose. Habib SM, Korte MR. Dialyse & Nefrologie Magazine 2012.

Encapsulating peritoneal sclerosis: een ingekapselde diagnose. Habib SM, Korte MR. ORPADT Forum 2012.

[Cytomegalovirus Pneumonitis in a patient with early stage chronic lymphocytic leukaemia]. [Article in Dutch] van Velsen EFS, Buster EHCJ, Cheung D, Keijman JMG, Riedl JA en Levin MD. NTvH: jaargang 9, nummer 6 – september 2012.

Richtlijnen behandeling multiple myeloom 2012. Zweegman S, Lokhorts HM, Levin MD, de Waal E, Bos GMJ, Kersten MJ, Ypma P,Klein SK, Minnema MC, Sonneveld P namens de myeloomwerkgroep van HOVON. NTvH 2012; 8: 300-320.

Influence of Age, C-Reactive Protein and D-dimer to diagnose Pulmonary Embolism. Crop M, Levin MD. Abstractboek 24e Internistendagen 2012.

De kunst van het kijken. de Lange JA, Levin MD, van der Velden JJAJ. NTvH 2012; 9: 249-250.

Implementation of a rapid responde system decreases the number of in-hospital cardiac arrests in a large teaching hospital. van Dijk E, Geense A, Ponssen H et al. Neth J of critical care, Abstract annual intensive care meeting 2012.

The implementation of a protocol “weanscreen” will lead to lower sedation levels, more frequent sedation stops and proper positioning in the ICU. le Grand M, Theunisse C, Ponssen H. Neth J of critical care, Abstract annual intensive care meeting 2012

Letter to the Editor. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. Smak Gregoor PJH. BMJ 2012;344:e4026.

Cardiovascular research: factor analysis for improved performance of diagnostic tests. Cleophas TJ, van Waardhuizen CN. Perfusion 2012; 194-203 47

Interne geneeskunde

Letter to the Editor. Sirolimus and skin-cancer prevention in kidney transplantation. Smak Gregoor PJ. N Engl J Med. 2012 Oct 18;367(16):1565; author reply 1565-6.

A 26 year old woman with a delayed, newly diagnosed myasthenia Gravis during pregnancy. de Pont J, Kerkhoff H, te Velde L. Neth J of critical care, Abstract annual intensive care meeting 2012

Severe valproic overdose treated with haemodialysis; a case report. de Fretes JLE, Arends JJ. Neth J of critical care, Abstract annual intensive care meeting 2012

Goodpasture’s syndrome: early diagnosis is essential. Bax NM, Arends JJ. Neth J of critical care, Abstract annual intensive care meeting 2012

Severe high anion gap acidosis due to therapeutic drugs. de Vette LC, Bax NM, te Velde LF. Neth J of critical care, Abstract annual intensive care meeting 2012

Voordrachten Incidence and consistence of lupus anticoagulant in deep venous thrombosis: A retrospective cohort study. van der Zwan M, Berendes P, Cheung D, Levin MD. 24e Internistendagen 2012.

Incidence of cardiotoxicity of Trastuzumab in Her2Neu positive breast cancer: A single centre experience. Liesting C, Kofflard M, Levin MD. Najaarscongres van de NVVC in Congrescentrum Papendal.

Clinical features of post‐transplantation encapsulating Peritoneal sclerosis (EPS); less inflammation, lower mortality and a different second hit compared to classical EPS. Korte MR. 14th Congress of the International Society of Peritoneal Dialysis (ISPD) 2012 Kuala Lampur. (Award Best Scientific Abstract)

A Dutch Guideline for the management of Encapsulating peritoneal sclerosis. Habib SM, Betjes MGH, Korte MR. European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress 2012, Paris.

Chirurgische interventie bij lokale encapsulerende peritoneale sclerose. Habib SM, Hagen SM, Korte MR, Zietse R, Dor FJMF, Betjes MGH.

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Chirurgendagen, Mei 2012, Veldhoven. (Award Best Scientific Abstract)

Encapsulating peritoneal sclerosis may evolve without systemic inflammation and absence of radiological abnormalities. Habib SM, Korte MR, Betjes MGH. Nederlandse Nefrologie Dagen April 2012.

Posters A Dutch Guideline for the management of Encapsulating peritoneal sclerosis. Habib SM, Betjes MGH, Korte MR. • 14th Congress of the International Society of Peritoneal Dialysis (ISPD), 2012 Kuala Lampur. • Nederlandse Nefrologie Dagen April 2012

Localized encapsulating peritoneal sclerosis constricting the terminal ileum; an unusual appearance requiring surgical intervention. Habib SM, Hagen SM, Korte MR, Zietse R, Dor FJMF, Betjes MGH. • Nederlandse Nefrologie Dagen April 2012. • European Renal Association-European Dialysis and Transplant Association (ERA-EDTA)

Congress 2012

• 14th Congress of the International Society of Peritoneal Dialysis (ISPD), 2012 Kuala Lampur

Clinical features of post‐transplantation encapsulating Peritoneal sclerosis (EPS); less inflammation, lower mortality and a different second hit compared to classical EPS. Habib SM, Korte MR, Betjes MGH. • Nederlandse Nefrologie Dagen April 2012. • European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress 2012

Encapsulating peritoneal sclerosis may evolve without systemic inflammation and absence of radiological abnormalities. Habib SM, Korte MR, Betjes MGH. • European Renal Association-European Dialysis and Transplant Association (ERA-EDTA)

Congress 2012.

• 14th Congress of the International Society of Peritoneal Dialysis (ISPD), 2012 Kuala Lampur.

Escalated dos Bortezomib once weekly combined with Lenalidomide and Dexamethasone (eVRD) followed by Lenalidomide maintenance in first relapse of multiple myeloma (MM). The HOVON 86 phase 2 trial. Sonneveld O, de Weerd O, Levin MD, Ghidey W, Vellenga E, Klein SK, Doorduyn J, Kersten MJ, Wijermans PW, Lokhorst H. Annual meeting American Society of Hematology 2012 Atlanta (abstract 1853)

Chirurgische interventie bij locale encapsulerende peritoneale sclerose. Habib SM, Korte MR, Zietse R, Dor FJMF, Betjes MGH. Chirurgendagen, mei 2012 Veldhoven.

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Interne geneeskunde

Keel, neus en oorheelkunde

PubMed publicaties Screening for hearing loss versus parental concern regarding hearing problems: Subsequent referral and treatment for otitis media in the Netherlands. Lok W, Anteunis LJ, Chenault MN, Meesters C, Haggard MP. Scand J Prim Health Care. 2012 Jul 15. [Epub ahead of print] OBJECTIVE: The present study investigates whether general practitioner (GP) consultation initiated by failing the population hearing screening at age nine months or GP consultation because of parental concern over ear/hearing problems was more important in deciding on referral and/or surgical treatment of otitis media (OM). DESIGN: A questionnaire covering the history between birth and 21 months of age was used to obtain information on referral after failing the hearing screening, GP consultations for ear/ hearing problems, and subsequent referral to a specialist and possible surgical treatment at an ENT department. SETTING: The province of Limburg, the Netherlands. Subjects. Healthy infants invited for the hearing screening at age nine months, who responded in an earlier study called PEPPER (Persistent Ear Problems, Providing Evidence for Referral, response rate 58%). Main outcome measures. The odds of a child being surgically treated for OM. RESULTS: The response rate for the present questionnaire was 72%. Of all children tested, 3.9% failed the hearing screening and were referred to their GP. Of all 2619 children in this study, 18.6% visited their GP with ear/hearing problems. Children failing the hearing screening without GP consultation for ear/hearing problems were significantly more often treated surgically for OM than children passing the hearing screening but with GP consultation for ear/hearing problems. CONCLUSION: Objectified hearing loss, i.e. failing the hearing screening, was important in the decision for surgical treatment in infants in the Netherlands. PMID: 22794165 [PubMed - as supplied by publisher]

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Kindergeneeskunde

PubMed publicaties Asymmetric polymicrogyria and periventricular nodular heterotopia due to mutation in ARX. Oegema R, Maat-Kievit A, Lequin MH, Schot R, Nanninga-van den Neste VM, Doornbos ME, de Wit MC, Halley DJ, Mancini GM. Am J Med Genet A. 2012 Jun;158A(6):1472-6. Mutations in the ARX gene, at Xp22.3, cause several disorders, including infantile spasms, X-linked lissencephaly with abnormal genitalia (XLAG), callosal agenesis and isolated intellectual disability. Genotype/phenotype studies suggested that polyalanine tract expansion is associated with non-malformative phenotypes, while missense and nonsense mutations cause cerebral malformations, however, patients with structural normal brain and missense mutations have been reported. We report on a male patient born with cleft lip and palate who presented with infantile spasms and hemiplegia. MRI showed agenesis of corpus callosum (ACC), an interhemispheric cyst, periventricular nodular heterotopia (PVNH), and extensive left frontal polymicrogyria (PMG). Sequencing of the ARX gene in the patient identified a six basepair insertion (c.335ins6, exon 2). The insertion leads to a two-residue expansion of the first polyalanine tract and was described previously in a family with non-syndromic X-linked mental retardation. To our knowledge, ARX mutation causing PMG and PVNH is unique, but the spasms and ACC are common in ARX mutations. Clinicians should be aware of the broad clinical range of ARX mutations, and further studies are necessary to investigate the association with PMG and PVNH and to identify possible modifying factors. PMID: 22585566 [PubMed - in process]

Urine Gonadotropin and Testosterone Levels in Male Very-Low-Birthweight Infants. de Jong M, Rotteveel J, Heijboer AC, Cranendonk A, Twisk JW, van Weissenbruch MM. Horm Res Paediatr. 2012 Oct 9:173-179. [Epub ahead of print] BACKGROUND: The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term-born infants, and may be important for reproductive function. Our objective was to investigate this activation of the hypothalamicpituitary-gonadal axis in male very-low-birthweight (VLBW) infants. Methods: Twenty-one VLBW boys (gestational age 26.0-30.0 weeks), participating in the NIRTURE trial, were included. Gonadotropin and testosterone levels were measured in serial urine samples collected at 1 and 4 weeks’ postnatal age, at 32 weeks’ postmenstrual age, at expected date of delivery and at the corrected age of 3 and 6 months. Results: Longitudinal analysis shows that after birth LH and FSH levels peak at a mean postnatal age of 1-4 weeks (mean postmenstrual age of 30-32 weeks) and decrease until 38 weeks’ postnatal age (corrected age of 6 months). Testosterone levels decrease with increasing age, and this decrease is faster in infants receiving early insulin therapy.

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Kindergeneeskunde

Conclusions: Serial urine sampling for measurement of gonadotropin and testosterone levels provides accurate information about the postnatal activation of the hypothalamicpituitary-gonadal axis in VLBW boys. FSH and LH levels peak at 1-4 weeks of age. Insulin treatment causes faster decrease in testosterone levels. PMID: 23051606 [PubMed - as supplied by publisher]

Rhabdomyolysis in a child with Hemoglobin SE. Tamminga RY, Doornbos ME, Muskiet FA, Koetse HA. Pediatr Hematol Oncol. 2012 Apr;29(3):267-9. PMID: 22475303 [PubMed - indexed for MEDLINE]

Patterns of Catch-Up Growth. de Wit CC, Sas TCJ, Wit JM, Cutfield WS. J Pediatr. 2012 Nov 13. [Epub ahead of print] PMID: 23153864 [PubMed - as supplied by publisher]

Urine gonadotropin and estradiol levels in female very-low-birth-weight infants. de Jong M, Rotteveel J, Heijboer AC, Cranendonk A, Twisk JW, van Weissenbruch MM. Early Hum Dev. 2012 Oct 4. [Epub ahead of print] BACKGROUND: The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term born infants and may be important for future reproductive function. AIM: The objective of this study was to investigate the postnatal activation of the hypothalamic-pituitary-gonadal axis in female very-low-birth-weight infants. STUDY DESIGN: We performed serial measurements of gonadotropin and estradiol levels in urine samples of female very-low-birth-weight infants collected at 1 and 4weeks postnatal age, at 32weeks postmenstrual age, at expected date of delivery and at the corrected age of three and six months. SUBJECTS: Twenty-two very-low-birth-weight infants (gestational age 25.4-30.1weeks), participating in the Neonatal Insulin Replacement Therapy in Europe trial, were included in this study. OUTCOME MEASURES: Gonadotropin and estradiol levels were measured in serial urine samples. RESULTS: Longitudinal analysis shows that after birth FSH and LH levels increase until 32weeks postmenstrual age (4weeks postnatal age) and then decrease until 3months corrected age (26weeks postnatal age). Estradiol levels decrease from 28weeks postmenstrual age (1week postnatal age) until 6months corrected age (39weeks postnatal age). CONCLUSIONS: Serial urine sampling for measurement of gonadotropin and estradiol levels provides an accurate description of the postnatal activation of the hypothalamic-pituitarygonadal axis in very-low-birth-weight girls. Levels of FSH and LH peak at a mean postmenstrual age of 32weeks (postnatal age of 4weeks) whereas estradiol levels are highest shortly after birth. PMID: 23041221 [PubMed - as supplied by publisher]

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Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome. Freriks K, Sas TCJ, Traas MA, Netea-Maier RT, den Heijer M, Hermus AR, Wit JM, van Alfenvan der Velden JA, Otten BJ, de Muinck Keizer-Schrama SM, Gotthardt M, Dejonckere PH, Zandwijken GR

, Menke LA, Timmers HJ.

Eur J Endocrinol. 2012 Dec 10;168(1):91-9. OBJECTIVE: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. DESIGN AND METHODS: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixty-eight women (Pl, n=23; Ox 0.03, n=27; and Ox 0.06, n=18) participated in the double-blind follow-up study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. RESULTS: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2±4.9 cm, Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. CONCLUSION: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilisation persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe. PMID: 23076845 [PubMed - in process]

[Mauriac syndrome-a rare complication of type 1 diabetes mellitus]. [Article in Dutch] Schmetz AV, Dekker-Maas MH, den Breejen MP, Sas TCJ. Ned Tijdschr Geneeskd. 2012;156(28):A4678. The treatment of children with type 1 diabetes mellitus has improved dramatically over the last few decades. The maintenance of acceptable metabolic control, nevertheless, remains challenging because the success of treatment is so dependent on patient compliance. Children with type 1 diabetes and poor metabolic control are at risk of developing Mauriac syndrome, a condition characterised by hepatomegaly, growth retardation and cushingoid features. A similar complication may occur in type-1 or type-2 adult diabetics; namely, glycogenic hepatopathy. We describe two children, a 12-year-old girl and a 16-year-old boy, who presented with classic symptoms of Mauriac syndrome. After metabolic control was achieved, reduction of hepatomegaly and the disappearance of cushingoid features were observed, proving the reversibility of the syndrome. Awareness that this syndrome still exists despite improved insulin therapy is crucial for earlier recognition and treatment. PMID: 22805790 [PubMed - indexed for MEDLINE]

53

Kindergeneeskunde

Overige publicaties Hoofdpijn bij kinderen: een praktische aanpak. Carbaat PAT, Graafland OM. Praktische Pediatrie september 2012; 3: 152-157.

Boek of hoofdstuk in boek Chapter ‘Growth and growth-promoting therapy in Turner Syndrome’. Handbook of Growth and Growth Monitoring in Health and Disease. Sas TCJ and de Muinck Keizer-Schrama SM. Editor: Preedy V; Springer 2012.

Klinische Richtlijn Syndroom van Turner. Nederlands-Vlaams Multidisciplinair Netwerk Turner Syndroom. Sas TCJ mede-auteur.

Voordrachten Maternaal SSRI gebruik in de zwangerschap, het postpartum beleid in Nederland bij de pasgeborene. Wakker-Deelen JE, Schmetz AVN, de Mol AC. Oral presentation. Nederlands – Vlaamse neonatologendag, 11 mei 2012, Utrecht, Nederland.

Timing of induction of puberty in girls with Turner syndrome and the effect on total pubertal growth and final height. Sas TCJ. Vergadering Adviesgroep Groeihormoon van de Nederlandse Vereniging voor Kindergeneeskunde, Juni 2012, Utrecht.

Timing of induction of puberty in girls with Turner syndrome and the effect on total pubertal growth and final height. Sas TCJ. 3rd Meeting of the NER Paediatric Group, Juni 2012, Leiden.

Turner syndroom: Dilemmas and Controversies concerning estrogens and androgens. Sas TCJ. KIGS meeting Pediatric Endocrinology, Oktober 2012, Berlijn, Duitsland.

Puberteitsinductie middels transdermale oestrogeenbehandeling. Sas TCJ. Mini symposium Klinische Richtlijn Turner Syndroom Nederland, Oktober 2012, Nijmegen Radboud Universitair Medisch Centrum.

54

Timing of induction of puberty in girls with Turner syndrome and the effect on total pubertal growth and final height. Sas TCJ. Landelijke Klinische Richtlijn syndroom van Turner, Oktober 2012, Nijmegen.

Dilemma and controversies in Turner syndroom - estrogens and androgens. Sas TCJ. Global Studies Meeting, Oktober 2012, Berlijn, Duitsland.

Een langdurige menarche, voordracht tijdens symposium kinderhematologie. Welborn KM, Cnossen MH. 34ste congres Nederlandse Vereniging voor Kindergeneeskunde, 1-11-2012, Veldhoven. Geaccrediteerd door Nederlandse Vereniging voor Kindergeneeskunde.

Levenslang leren. IFMS-A&A. Drexhage V. NVMO congres, November 2012, Maastricht.

Neonatale ECMO en risicofactoren voor de hersenen. de Mol AC. Wetenschapsdag 2012, Juni, ASZ, Dordrecht.

Posters Differences in postpartum policy after maternal use of selective serotonin reuptake inhibitors during pregnancy. Wakker-Deelen JE, de Mol AC. 4th Congress of the European Academy of Paediatric Societies (EAPS/ESPR) October 2012, Istabul, Turkey.

Maternaal SSRI gebruik in de zwangerschap, beleid bij de pasgeborene. Wakker-Deelen JE, Schmertz A, de Mol AC. Wetenschapsdag 2012, Juni, ASZ, Dordrecht.

55

Kindergeneeskunde

Klinische chemie

PubMed publicaties The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia Castel R, Tax MG, Droogendijk J, Leers MP, Beukers R, Levin MD, Sonneveld P, Berendes PB. ClinChem Lab Med. 2012 Feb 11;50(8):1343-9. BACKGROUND: Serum ferritin is the best single laboratory test to diagnose irondeficiency anemia (IDA). Ferritin levels <20 μg/L are highly specific for IDA,and ferritin levels >100 μg/L usually exclude IDA. However, ferritinconcentrations between 20 and 100 μg/L are often inconclusive. The objective ofthis study was to improve the diagnosis of IDA when ferritin levels areinconclusive. METHODS: We evaluated the predictive performance of classic (ferritin, meancorpuscular volume, transferrin and serum iron) and modern [reticulocytehemoglobin content, serum transferrin receptor and soluble transferrin receptor(sTfR)/log(ferr)] iron status parameters to diagnose IDA in 2084 anemic,non-hospitalized patients. The results were validated in an independent cohort of274 anemic patients. RESULTS: In our study population, 29% (595 patients) of the patients had aferritin level between 20 and 100 μg/L, hampering diagnosis of IDA. None of theclassic or modern parameters was capable of completely separating the IDApopulation from the non-IDA population. However, using a new parameter, thetransferrin/log(ferritin) ratio, the IDA and non-IDA populations can becompletely separated. At a cut-off value of 1.70, the transferrin/ log(ferritin)ratio indicates IDA in 29% of the patients with inconclusive ferritin levels. CONCLUSIONS: The transferrin/log(ferritin) ratio is a practical new tool thatimproves diagnosis of iron deficiency when ferritin levels are inconclusive. PMID: 22868798 [PubMed - indexed for MEDLINE]

Overige publicaties Measuring LDL-cholesterol: are we doing it wrong? van der Heul-Nieuwenhuijsen L, Stek S, Tax M, Verheijen F, Vermeer E. Ned Tijdschr Klin Chem Labgeneesk 2012; 37: 221-222.

Wel of geen duplometing bij een INR groter dan vijf op de Sysmex CA7000? van der Heul-Nieuwenhuijsen L, Visser P, Berendes PB. Ned Tijdschr Klin Chem Labgeneesk 2012; 37: 244-246

Watch the walnuts: severe immune thrombocytopenia after consumption of English walnuts. Vermeer HJ, Achterbergh R, Porcelijn L, Aster RH, Deenik W, Damne-Gubbels C, Curtis BR. Ned Tijdschr Klin Chem Labgeneesk 2012; 37: 232-233.

56

Voordrachten Reductie kosten bloedproducten. Berendes PB. Symposium kliniek van bloedtransfusies, 5 juni te Rotterdam.

Is therapeutic quality influenced by choice of thromboplastin? Berendes PB. ECAT-symposium, 8 november te Leiden.

Posters Friedewald equation already underestimates low-density lipoprotein cholesterol at triglyceride concentrations of >2 mmol/L. van der Heul-Nieuwenhuijsen L, Stek S, Tax M, Verheijen F, Vermeer E. Nationale Wetenschapsdag Klinische Chemie, Amersfoort, 19 april 2012.

57

Klinische fysica

Klinische fysica

Voordrachten Diagnostische monitoren voor radiologie – klinische en technische vergelijking. Leung KYE, Niehof SP, Bosman J. Jaarcongres Nederlandse Vereniging voor Klinische Fysica, 30-31 maart 2012, Woudschoten.

Quality Control of Color Uniformity in Diagnostic Displays. Leung KYE, Niehof SP, Bosman J. World Congress Medical Physics and Biomedical Engineering, 26-31 may 2012, Beijing China.

Posters Image Quality Control For Clinical Ultrasound Equipment. Niehof S, van den Berg - De Bakker B, Leung KYE, Bosman J. Jaarcongres Nederlandse Vereniging voor Klinische Fysica, 30-31 maart 2012, Woudschoten.

Image Quality Control For Clinical Ultrasound Equipment. Niehof S, van den Berg - De Bakker B, Leung KYE, Bosman J. World Congress Medical Physics and Biomedical Engineering, 26-31 may 2012, Beijing China.

58

Klinische geriatrie

Boek of hoofdstuk in boek Effectieve communicatie met ouderen. Meinardi MC. Compendium Behandeling van kanker bij ouderen. Den Haag:Academic Pharmaceutical Productions B.V., 2012. ISBN 978 90 5761 117 9

Voordrachten Total Nutrition Therapy. Course Meinardi MC. 2 daagse internationale cursus geacrediteerd door de EUGMS(European Union Geriatric Medicine Society), 8-9 maart 2012 Den Haag, 15-16 maart 2012 Oosterbeek.

Posters De Retitest, Een snelle computertest aan het bureau van de arts, om aandacht te meten. Groot ER. Geriatriedagen, 8-10 februari 2012, Den Bosch

59

Leerhuis

Leerhuis

Overige publicaties Cardiovascular research: factor analysis for improved performance of diagnostic tests. Cleophas TJ, van Waardhuizen CN. Perfusion 2012; 25: 194–203.

Voordrachten The development of an instrument to measure student’s non-verbal behaviour in feedback situations. van de Ridder JMM, Collast-van Dijk HEC, Govers L, Stokking KM, ten Cate TJ. 15th Ottawa Conference Assessment of Competence in Medicine and the Healthcare professions, Kuala Lumpur Malaysia, 9 – 13 maart 2012.

Is the formative assessment process for surgical residents reliable? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. 15th Ottawa Conference Assessment of Competence in Medicine and the Healthcare professions, Kuala Lumpur Malaysia, 9 – 13 maart 2012.

Overleven de consultvaardigheden aangeleerd in de opleiding tijdens de co- schappen? Aper L, Reniers J, Koole S, Valcke M, van de Ridder JMM, Derese A. Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Wat zijn de klachten van patiënten over AIOS en welke kosten brengt dit met zich mee? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Evalueren van het leerklimaat: hoe vaak eigenlijk? Oostenbroek RJ, Plaisier PW, van de Ridder JMM, AAV- bestuur. Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Hoe kan de medisch staf in algemene ziekenhuizen bij opleiden betrokken worden? van de Ridder JMM, Bommel EFH van, Koopman-van Gemert AWMM, Oostenbroek RJ, Verheijen FM, Zanting A, Plaisier PW. Round table session presented at the Nederlandse Vereniging voor Medisch Onderwijs Congres, , November 14-16 2012, Maastricht.

60

Forensische geneeskunde: een vak apart EN een apart vak. Wat kunnen we er VAN leren NVMO Werkgroep PMO. Verwijnen GM, van de Ridder JMM, Haneveld R. Round table session presented at the Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Intervisie. Hulshoff LJ, Bleker WA den, van de Ridder JMM. Workshop presented at the Nederlandse Vereniging voor Medisch Onderwijs Congres, Maastricht, the Netherlands, November 14-16, 2012.

Levenslang leren en ontwikkelen door medische professionals: van ‘competentiegericht’ opleiden naar individuele ‘Appraisal and Assessment’. So RKL, Drexhage V, van de Ridder JMM. Workshop presented at the Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Young medical educators’ workshop: Collaborative Research in Medical Education: strategies, benefits, pitfalls. Huwendiek S, van de Ridder JMM, Amin Z, Petroni Mennin R, Ringsted C, Mennin S. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

How do non-verbal and verbal communication affect feedback dialogues? van de Ridder JMM, Collast -van Dijk HEC, Stokking KM, Cate, TJ ten. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

OSCE feedback and debriefing – enhancing the “formative” in formative assessments. van de Ridder JMM, Kachur E, Errichetti A, Parish S, Schwartz C. 15th Ottawa Conference on the Assessment of Competence in Medicine and the Healthcare Professions, March 9-13 2012, Kuala Lumpur Malaysia.

The development of an instrument to measure students’ non-verbal behaviour in feedback situations. van de Ridder JMM, Collast-van Dijk HEC, Govers L, Stokking KM, Cate TJ ten. 15th Ottawa Conference on the Assessment of Competence in Medicine and the Healthcare Professions, March 9-13 2012, Kuala Lumpur Malaysia.

Is the formative assessment process for surgical residents reliable? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. 15th Ottawa Conference on the Assessment of Competence in Medicine and the Healthcare Professions, March 9-13 2012, Kuala Lumpur Malaysia.

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Leerhuis

Posters Residents’ perceptions of assessment and feedback in a surgical department: supervisors must do better! Oostenbroek RJ, Plaisier PW, van de Ridder JMM. 15th Ottawa Conference Assessment of Competence in Medicine and the Healthcare professions, Kuala Lumpur Malaysia, 9 – 13 maart 2012.

Themaweek ‘leren’. de Bruijn CN, Reedeker AF, van de Ridder JMM, Bleker W. Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Verbaal en nonverbaalgedrag in feedbackdialogen: een literatuurstudie. van de Ridder JMM, Collast-van Dijk HEC, Stokking KM, Cate ThJ ten. Nederlandse Vereniging voor Medisch Onderwijs Congres, November 14-16 2012, Maastricht.

Residents prefer to evaluate the Educational Climate more often than supervisors consider this necessary! Plaisier PW, van de Ridder JMM, Oostenbroek RJ. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

Emergency physicians as role models – without having had a role model themselves, is that possible? Spruyt C, Dautzenberg B, van de Ridder JMM. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

Do consultation skills survive in clinical clerkships? Aper L, van de Ridder JMM. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

What are patients’ complaints about residents and what are the costs? Oostenbroek RJ, Plaisier PW, van de Ridder JMM. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

Internal audit as a preparation for an external audit. Oostenbroek RJ, van de Ridder JMM, Derksen M. Association for Medical Education in Europe 2012 Conference, August 25-29 2012, Lyon France.

62

Longgeneeskunde

PubMed Publicaties Negative NKX2-1 (TTF-1) as Temporary Surrogate Marker for Treatment Selection During EGFR-Mutation Analysis in Patients with Non-Small-Cell Lung Cancer. Vincenten J, Smit EF, Vos W, Grünberg K, Postmus PE, Heideman DA, Snijders PJ, Meijer G, Kuik J, Witte BI, Thunnissen E. J Thorac Oncol. 2012 Oct;7(10):1522-7. INTRODUCTION: In the past decade, major progress has been made toward personalized medical treatment of non-small-cell lung cancer (NSCLC) through the discovery of epithelial growth factor receptor (EGFR) mutations. However, mutation analysis takes extra time and additional costs in the diagnostic evaluation of lung cancer patients. It has been hypothesized that EGFR mutations are restricted to terminal respiratory unit -type adenocarcinoma expressing thyroid transcription factor-1 (official symbol NKX2-1) as determined by immunohistochemistry. The aim of the current study is to evaluate the potential of NKX2-1 immunohistochemistry as a prescreening test for EGFR mutation analysis. METHODS: From 2004 to December 2010, 810 consecutive NSCLC tumor specimens were tested for EGFR mutations in a routine diagnostic procedure. Immunohistochemistry for NKX2-1 was performed (clone 8G7G3/1 [Dako]) and the results were compared with tumor EGFR-mutation status and clinicopathological characteristics. RESULTS: EGFR mutations were detected in 114 specimens (14%). NKX2-1 expression was present in 68%. In the cases with EGFR mutation, NKX2-1 staining was positive in 92%. NKX2-1 immunohistochemical (IHC) staining was significantly associated with the presence of EGFR mutations (p = 5.3×10). NKX2-1 increased the negative predictive value in NSCLC to more than 95%. CONCLUSIONS: In case of a negative NKX2-1 IHC staining, and only if clinically urgent, the high negative predictive value of more than 95% for EGFR mutations is a suitable temporary surrogate marker for the choice of starting with chemotherapy. In case of positive NKX2-1 IHC, the best strategy is to wait for the outcome of EGFR-mutation analysis and then choose the appropriate treatment. PMID: 22982653 [PubMed - in process]

Pubmed collaborative authorship publicaties Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease. van den Berge M, Hop WC, van der Molen T, van Noord JA, Creemers JP, Schreurs AJ, Wouters EF, Postma DS; COSMIC (COPD and Seretide: a Multi-Center Intervention and Characterization) study group. Collaborator: ...Hol BEA… Respir Res. 2012 Jun 6;13:44.

63

Longgeneeskunde

BACKGROUND: Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD. METHODS: In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations. RESULTS: There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70. CONCLUSIONS: Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice. PMCID: PMC3494574 PMID: 22672621 [PubMed - in process]

Overige publicaties Applying biomarker testing to clinical practice in lung cancer. Vincenten J, Smit EF, Ylstra B, Thunnissen E. Lung Cancer Management August 2012, Vol. 1, No. 2, Pages 145-154.

Voordrachten De organisatie van integrale slaapapneu diagnose. Hol BEA. Landelijk Wetenschappelijk symposium ‘Rondom de Diagnose’ 29 november 2012 Nunspeet. Geaccrediteerd door o.a. de NVALT (Nederlandse vereniging voor artsen longziekten en tuberculose).

64

Maag, darm en lever

PubMed Publicaties The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia. Castel R, Tax MGHM, Droogendijk J, Leers MPG, Beukers R, Levin M-D, Sonneveld P, Berendes PB. Clin Chem Lab Med. 2012 Feb 11;50(8):1343-9. BACKGROUND: Serum ferritin is the best single laboratory test to diagnose iron deficiency anemia (IDA). Ferritin levels <20 μg/L are highly specific for IDA, and ferritin levels >100 μg/L usually exclude IDA. However, ferritin concentrations between 20 and 100 μg/L are often inconclusive. The objective of this study was to improve the diagnosis of IDA when ferritin levels are inconclusive. METHODS: We evaluated the predictive performance of classic (ferritin, mean corpuscular volume, transferrin and serum iron) and modern [reticulocyte hemoglobin content, serum transferrin receptor and soluble transferrin receptor (sTfR)/log(ferr)] iron status parameters to diagnose IDA in 2084 anemic, non-hospitalized patients. The results were validated in an independent cohort of 274 anemic patients. RESULTS: In our study population, 29% (595 patients) of the patients had a ferritin level between 20 and 100 μg/L, hampering diagnosis of IDA. None of the classic or modern parameters was capable of completely separating the IDA population from the non-IDA population. However, using a new parameter, the transferrin/log(ferritin) ratio, the IDA and non-IDA populations can be completely separated. At a cut-off value of 1.70, the transferrin/ log(ferritin)ratio indicates IDA in 29% of the patients with inconclusive ferritin levels. CONCLUSIONS: The transferrin/log(ferritin) ratio is a practical new tool that improves diagnosis of iron deficiency when ferritin levels are inconclusive. PMID: 22868798 [PubMed - in process]

The 2012 revised Dutch national guidelines for the treatment of chronic hepatitis B virus infection. Buster EH, Baak BC, Bakker CM, Beuers UH, Brouwer JT, Drenth JP, van Erpecum KJ, van Hoek B, Honkoop P, Kerbert-Dreteler MJ, Koek GH, van Nieuwkerk KM, van Soest H, van der Spek BW, Tan AC, Vrolijk JM, Janssen HL. Neth J Med. 2012 Oct;70(8):381-5. In 2008, the Netherlands Association of Gastroenterologists and Hepatologists (Nederlands Vereniging van Maag-Darm-Leverartsen) published the Dutch national guidelines for the treatment of chronic hepatitis B virus infection. New insights into the treatment of chronic hepatitis B with relevance for clinical practice have been adopted in these concise, revised guidelines. The most important changes include the choice of initial antiviral therapy, licensing of tenofovir for the treatment of chronic hepatitis B and the management of antiviral resistance. PMID: 23065990 [PubMed - in process] 65

Maag, darm en lever

[Revision of the practical guideline ‘Treatment of chronic viral hepatitis B infection]. [Article in Dutch] Honkoop P, Tan AC. Ned Tijdschr Geneeskd. 2012;156(37):A5139. This article contains our comments on the practical guideline for treating chronic hepatitis B in the Netherlands, which was published in 2008. Revision of this guideline had already become necessary in 2011 due to rapidly changing therapeutic strategies. New secondgeneration drugs show minimal antiviral resistance and their use should be considered more frequently. In addition, certified multidisciplinary centres of expertise should contribute to the improvement of care for patients with chronic hepatitis B. Our opinion is that the revisions make the guideline for treating chronic hepatitis B more complete and up to date. PMID: 22971432 [PubMed - in process]

Yield of routine molecular analyses in colorectal cancer patients ≤70 years to detect underlying Lynch syndrome. van Lier MG, Leenen CH, Wagner A, Ramsoekh D, Dubbink HJ, van den Ouweland AM, Westenend PJ, de Graaf EJ, Wolters LM, Vrijland WW, Kuipers EJ, van Leerdam ME, Steyerberg EW, Dinjens WN; LIMO Study Group. J Pathol. 2012 Apr;226(5):764-74. doi: 10.1002/path.3963. Epub 2012 Jan 17.

Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients ≤70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged ≤50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients ≤70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (≤50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients. PMID: 22081473 [PubMed - indexed for MEDLINE]

66

Medische microbiologie

Pubmed collaborative authorship publicaties Decontamination of cephalosporin-resistant Enterobacteriaceae during selective digestive tract decontamination in intensive care units. Oostdijk EA, de Smet AM, Kesecioglu J, Bonten MJ; on behalf of the Dutch SOD-SDD Trialists Group. Collaborators: … Frénay IH, Maraha B … J Antimicrob Chemother. 2012 May 29. [Epub ahead of print] OBJECTIVES: Prevalences of cephalosporin-resistant Enterobacteriaceae are increasing globally, especially in intensive care units (ICUs). The effect of selective digestive tract decontamination (SDD) on the eradication of cephalosporin-resistant Enterobacteriaceae from the intestinal tract is unknown. We quantified eradication rates of cephalosporin-resistant and cephalosporin-susceptible Enterobacteriaceae during SDD in patients participating in a 13 centre cluster-randomized study and from a single-centre cohort. METHODS: All SDD patients colonized with Enterobacteriaceae in the intestinal tract at ICU admission were included. Cephalosporin resistance was defined as resistance to ceftazidime, cefotaxime or ceftriaxone and aminoglycoside resistance as resistance to tobramycin or gentamicin. Duration of rectal colonization was determined by screening twice weekly during ICU stay. Swabs were inoculated on selective medium supplemented with tobramycin or cefotaxime. RESULTS: Five hundred and seven (17%) of 2959 SDD patients with at least one rectal sample were colonized with Enterobacteriaceae at ICU admission: 77 (15%) with cephalosporin-resistant Enterobacteriaceae and 50 (10%) with aminoglycoside-resistant Enterobacteriaceae. Fifty-six (73%) patients colonized with cephalosporin-resistant Enterobacteriaceae were successfully decontaminated before ICU discharge, as were 343 (80%) patients colonized with cephalosporin-susceptible Enterobacteriaceae (P = 0.17). For aminoglycoside resistance, 31 (62%) patients were decontaminated, as were 368 patients (81%)colonized with aminoglycosidesusceptible Enterobacteriaceae (P < 0.01). On average, decolonization was demonstrated after 4 days if colonized with cephalosporin-susceptible Enterobacteriaceae and aminoglycoside-susceptible Enterobacteriaceae, and after 5 and 5.5 days if colonized with cephalosporinresistant Enterobacteriaceae and aminoglycoside-resistant Enterobacteriaceae, respectively (log-rank test P = 0.053 for cephalosporin resistance and P = 0.03 for aminoglycoside resistance). If eradication failed, no associations were found with increased resistance in time (P > 0.05 for all comparisons). CONCLUSIONS: SDD can successfully eradicate cephalosporin-resistant Enterobacteriaceae from the intestinal tract. PMID: 22643189 [PubMed - as supplied by publisher]

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Medische microbiologie

Invasive pneumococcal disease and 7-valent pneumococcal conjugate vaccine, the Netherlands. van Deursen AM, van Mens SP, Sanders EA, Vlaminckx BJ, de Melker HE, Schouls LM, de Greeff SC, van der Ende A; Invasive Pneumococcal Disease Sentinel Surveillance Laboratory Group. Colloborator: … Frénay IH… Emerg Infect Dis. 2012 Nov;18(11):1729-37. In the Netherlands, the national immunization program includes 7-valent pneumococcal conjugate vaccine (PCV7) for all newborns born after April 1, 2006. We compared the incidence of invasive pneumococcal disease (IPD) and patient and disease characteristics before PCV7 introduction (June 2004-June 2006) with those after PCV7 introduction (June 2008-June 2010). Culture-confirmed IPD cases were identified by 9 sentinel laboratories covering ≈25% of the Dutch population. Significant declines in overall IPD incidence were observed in children <2 (60%) and in persons >65 (13%) years of age. A trend toward gradual increases in non-PCV7 serotype IPD infections was observed in all age groups; the largest increases were among persons 50-64 (37%) and >65 (25%) years of age. In adults, the proportion of immunocompromised persons increased among IPD patients. Overall, deaths from IPD decreased from 16% to 12% because of a lower case-fatality rate for persons with non-PCV7 serotype IPD. PMCID: PMC3559145 PMID: 23092683 [PubMed - indexed for MEDLINE]

Voordrachten Emerging outbreaks of Clostridium difficile in regional long-term care facilities. Verspui-van der Eijk PA, Frénay IH, Kuijper EJ. European Congress for Clinical Microbiology and Infectious Diseases, 31 March 2012 – 3 April 2012, London England.

Infecties, antibiotica en resistentie bij micro-organismen in verpleeghuizen. Frénay IH. Regiobijeenkomst VERENSO, 23 april 2012, Rotterdam.

ISIS-AR (Infectious Disease Surveillance Information System for Antibiotic Resistance): Urineweginfecties en antibiotica resistentie ontwikkeling in verpleeghuizen. Frénay IH. Deelnemersdag SNIV (Surveillance Netwerk Infectieziekten Verpleeghuizen) RIVM, 28 september 2012, De Reehorst Driebergen.

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PubMed publicaties Interobserver agreement in case history evaluation in carpal tunnel syndrome. Westerman D, Kerkhoff H, Visser GH, Kleyweg RP. J Clin Neuromuscul Dis. 2012 Jun;13(4):196-200. OBJECTIVES: The case history is the cornerstone for the diagnosis of carpal tunnel syndrome (CTS). The value of neurological examination in CTS seems limited. In this study, we investigated the interobserver agreement in case history of CTS and the potential additional value of neurological examination. METHODS: Case history was taken and neurological examination was done in all patients referred for a possible CTS during a 6-month period. This was done independently by 2 senior neurologists. RESULTS: We studied 119 patients. The interobserver agreement for the conclusion of CTS after history was high (k = 0.79). Neurological examination rarely changed the diagnosis based on the case history. CONCLUSIONS: This study shows a high interobserver agreement in the diagnosis of CTS based on patient history alone. Neurological examination rarely changed this diagnosis, suggesting a prominent role for the case history and a limited role for neurological examination. This may have practical implications. PMID: 22622163 [PubMed - in process]

Asymmetric polymicrogyria and periventricular nodular heterotopia due to mutation in ARX. Oegema R, Maat-Kievit A, Lequin MH, Schot R, Nanninga-van den Neste VM, Doornbos ME, de Wit MC, Halley DJ, Mancini GM. Am J Med Genet A. 2012 Jun;158A(6):1472-6. Mutations in the ARX gene, at Xp22.3, cause several disorders, including infantile spasms, X-linked lissencephaly with abnormal genitalia (XLAG), callosal agenesis and isolated intellectual disability. Genotype/phenotype studies suggested that polyalanine tract expansion is associated with non-malformative phenotypes, while missense and nonsense mutations cause cerebral malformations, however, patients with structural normal brain and missense mutations have been reported. We report on a male patient born with cleft lip and palate who presented with infantile spasms and hemiplegia. MRI showed agenesis of corpus callosum (ACC), an interhemispheric cyst, periventricular nodular heterotopia (PVNH), and extensive left frontal polymicrogyria (PMG). Sequencing of the ARX gene in the patient identified a six basepair insertion (c.335ins6, exon 2). The insertion leads to a two-residue expansion of the first polyalanine tract and was described previously in a family with non-syndromic X-linked mental retardation. To our knowledge, ARX mutation causing PMG and PVNH is unique, but the spasms and ACC are common in ARX mutations. Clinicians should be aware of the broad

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clinical range of ARX mutations, and further studies are necessary to investigate the association with PMG and PVNH and to identify possible modifying factors. PMID: 22585566 [PubMed - in process]

[Initial reactions of patients after a stroke: more than half undertake no action]. [Article in Dutch] Zock E, Kerkhoff H, Kleyweg RP. Ned Tijdschr Geneeskd. 2012;156(25):A4336. OBJECTIVE: To gain insight into patient awareness of symptoms associated with a TIA or stroke and the speed at which medical help is sought. DESIGN: Observational study. METHODS: The study was conducted with patients admitted to our Stroke Care Unit after having experienced a TIA or stroke. A questionnaire was used to collect information on external factors such as the initial reaction of the patient, the presence of a bystander and knowledge about stroke. This questionnaire consisted of 18 closed questions and 2 open questions. RESULTS: We included 105 patients who had experienced a TIA or an ischemic or haemorrhagic stroke. Mean age was 71.6 years. Overall, 54% of these patients had undertaken no action within an hour of their first symptoms. The main reasons for this were a lack of insight into the symptoms associated with stroke or the expectation that the symptoms would disappear (73%). It appeared that 35% of these patients were not able to name one or more symptoms associated with a stroke. CONCLUSION: Patient knowledge of stroke and the awareness of the importance of urgent medical help are insufficient. These are important factors causing delay in rapid treatment with thrombolytics. National research is needed to explore whether our results are comparable to those in other regions of the Netherlands. PMID: 22748365 [PubMed - indexed for MEDLINE]

Pubmed collaborative authorship publicaties Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Zinkstok SM, Roos YB; ARTIS investigators. Collaborator:… Kerkhoff H … Lancet. 2012 Aug 25;380(9843):731-7. Epub 2012 Jun 28. BACKGROUND: Thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. After alteplase-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after alteplase could reduce the risk of reocclusion and improve outcome. We compared the effects of early addition of intravenous aspirin to alteplase with standard alteplase without aspirin. METHODS: In this multicentre, randomised, open-label trial with blind-endpoint assessment, patients with acute ischaemic stroke treated with alteplase were randomly assigned to 300 mg intravenous aspirin within 90 min after start of alteplase treatment or to no additional

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treatment. In both groups, oral antiplatelet therapy was started 24 h after alteplase treatment. The primary endpoint was favourable outcome, defined as a score of 0-2 on the modified Rankin scale at 3 months. This trial is registered with the Netherlands Trial Register (NTR822). FINDINGS: Between July 29, 2008, and April 20, 2011, 642 patients (322 patients aspirin, 320 patients standard treatment) of the targeted 800 patients were enrolled. At that time, the trial was terminated prematurely because of an excess of symptomatic intracranial haemorrhage (SICH) and no evidence of benefit in the aspirin group. At 3 months, 174 (54·0%) patients in the aspirin group versus 183 (57·2%) patients in the standard treatment group had a favourable outcome (absolute difference -3·2%, 95% CI -10·8 to 4·2; crude relative risk 0·94, 0·82 to 1·09, p=0·42). Adjusted odds ratio was 0·91 (95% CI 0·66-1·26, p=0·58). SICH occurred more often in the aspirin group (14 [4·3%] patients) than in the standard treatment group (five [1·6%]; absolute difference 2·8%, 95% CI 0·2-5·4; p=0·04). SICH was more often the cause of poor outcome in the aspirin group compared with the standard treatment group (11 vs 1, p=0·006). INTERPRETATION: Early administration of intravenous aspirin in patients with acute ischaemic stroke treated with alteplase does not improve outcome at 3 months and increases the risk of SICH. The results of this trial do not support a change of the current guidelines, which advise to start antiplatelet therapy 24 h after alteplase. FUNDING: The Dutch Heart Foundation. PMID: 22748820 [PubMed - indexed for MEDLINE]

Overige publicaties Eerste reactie van patiënten na het ontstaan van een beroerte. Zock E, Kerkhoff H, Kleyweg RP. Ned Tijdschr Geneeskd. 2012;156:A4336.

Hoofdpijn bij kinderen: een praktische aanpak. Carbaat PAT, Graafland OM. Praktische Pediatrie september 2012; 3: 152-157.

A 26-year old woman with a delayed , newly diagnosed myasthenia gravis during pregnancy. Pont de JJK, Kerkhoff H, Velde te LF. NVIC Nederlandse Intensivistendagen, Ede, februari 2012.

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Orthopedie

PubMed publicaties No positive bone healing after using platelet rich plasma in a skeletal defect. An observational prospective cohort study. Peerbooms JC, Colaris JW, Hakkert AA, Van Appeldorn M, Bruijn DJ, Den Oudsten BL, Gosens T. Int Orthop. 2012 Jun 26. [Epub ahead of print] PURPOSE: Platelet rich plasma (PRP) is derived from the patient’s own blood. The activated blood platelets release a cocktail of growth factors, some of which are thought to initiate and stimulate repair. We compared two groups to investigate whether the use of PRP mixed with bone chips improves bone healing in patients with a skeletal defect. METHODS: In total, 41 patients were observed. One group underwent a high tibial osteotomy with the addition of PRP and bone chips in the open wedge. The other group underwent the same procedure without the addition of PRP. Six patients had to be excluded because of insufficient data or they ere lost to follow-up. Bone healing was studied using computed tomography scanning. The blood was sequestered and PRP was produced using a blood cell separator with a PRP software program (Electa, Sorin Group, Mirandola, Italy). RESULTS: Analysis focused on the remaining 35 patients. At baseline, there were no differences between the two groups for age, sex and side of operation. At one week postoperatively, the bone density under (p = 0.02) and above the wedge was significantly lower in the PRP group than the control group (p = 0.24). At six weeks postoperatively, no significant differences between the treatment groups were found. At 12 weeks, the PRP group had significantly lower bone density under the wedge compared to the control group (p = 0.01). CONCLUSIONS: We found that patients with a skeletal defect did not benefit from the application of PRP mixed with an allograft regarding bone healing. PMID: 22733441 [PubMed - as supplied by publisher]

Overige publicaties Een hardloper met pijnlijke hielen. van Gool R, Pepels WRJ. Ned Tijdschr Geneeskd. 2012;156:A3346.

Voordrachten Ongoing positive effect of platelet rich plasma in lateral epicondylitis after 2 years: an RCT. Gosens T, Peerbooms JC, den Oudsten BL. AAOS, 7 – 11 february 2012, San Francisco USA.

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PubMed publicaties Bladder polyps following Avaulta anterior mesh vaginal wall repair. Auzin M, Teune TM, Hogewoning CJ. Int Urogynecol J. 2012 Apr 25. [Epub ahead of print] We present the case of a postmenopausal woman who developed bladder polyps leading to serious abdominal pain, dysuria with mucus and blood, and urinary incontinence after anterior vaginal wall repair using Avaulta anterior mesh(Bard®). All of these symptoms resolved after mesh removal. This case emphasizes that not all complications of mesh are known. PMID: 22531953 [PubMed - as supplied by publisher]

Regulation of steroidogenesis in a primary pigmented nodular adrenocortical disease-associated adenoma leading to virilization and subclinical Cushing’s syndrome. Hofland J, de Herder WW, Derks L, Hofland LJ, van Koetsveld PM, de Krijger RR, van Nederveen FH, Horvath A, Stratakis CA, de Jong FH, Feelders RA. Eur J Endocrinol. 2012 Dec 10;168(1):67-74. CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD) can lead to steroid hormone overproduction. Mutations in the cAMP protein kinase A regulatory subunit type 1A (PRKAR1A) are causative of PPNAD. Steroidogenesis in PPNAD can be modified through a local glucocorticoid feed-forward loop. OBJECTIVE: Investigation of regulation of steroidogenesis in a case of PPNAD with virilization. MATERIALS AND METHODS: A 33-year-old woman presented with primary infertility due to hyperandrogenism. Elevated levels of testosterone and subclinical ACTH-independent Cushing’s syndrome led to the discovery of an adrenal tumor, which was diagnosed as PPNAD. In vivo evaluation of aberrantly expressed hormone receptors showed no steroid response to known stimuli. Genetic analysis revealed a PRKAR1A protein-truncating Q28X mutation. After adrenalectomy, steroid levels normalized. Tumor cells were cultured and steroidogenic responses to ACTH and dexamethasone were measured and compared with those in normal adrenal and adrenocortical carcinoma cells. Expression levels of 17β-hydroxysteroid dehydrogenase (17β-HSD) types 3 and 5 and steroid receptors were quantified in PPNAD, normal adrenal, and adrenal adenoma tissues. RESULTS: Isolated PPNAD cells, analogous to normal adrenal cells, showed both increased steroidogenic enzyme expression and steroid secretion in response to ACTH. Dexamethasone did not affect steroid production in the investigated types of adrenal cells. 17β-HSD type 5 was expressed at a higher level in the PPNAD-associated adenoma compared with control adrenal tissue.

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CONCLUSION: PPNAD-associated adenomas can cause virilization and infertility by adrenal androgen overproduction. This may be due to steroidogenic control mechanisms that differ from those described for PPNAD without large adenomas. PMID: 23065993 [PubMed - indexed for MEDLINE]

Melanocortin 2 receptor-associated protein (MRAP) and MRAP2 in human adrenocortical tissues: regulation of expression and association with ACTH responsiveness. Hofland J, Delhanty PJ, Steenbergen J, Hofland LJ, van Koetsveld PM, van Nederveen FH, de Herder WW, Feelders RA, de Jong FH. J Clin Endocrinol Metab. 2012 May;97(5):E747-54. CONTEXT: ACTH stimulates adrenocortical steroid production through the melanocortin 2 receptor (MC2R). MC2R trafficking and signaling are dependent on the MC2R accessory protein (MRAP). The MRAP homolog MRAP2 also transports the MC2R to the cell surface but might prevent activation. OBJECTIVE: The objective of the investigation was to study the regulatory pathways of MRAP and MRAP2 and their contributions to ACTH responsiveness in human adrenal tissues. DESIGN AND SETTING: MRAP, MRAP2, and MC2R expression levels were studied in 32 human adrenocortical samples. Regulation of these mRNAs was investigated in 43 primary adrenal cultures, stimulated with ACTH, forskolin, angiotensin II (AngII), phorbol-12-myristate13-acetate (PMA), or dexamethasone. The induction of cortisol, cAMP, and ACTH-responsive genes after treatment with ACTH was related to MRAP, MRAP2, and MC2R expression levels. RESULTS: MRAP and MRAP2 levels were lower in adrenocortical carcinomas (ACC) than in other adrenal tissues (P < 0.001). Patient ACTH and cortisol levels were associated with adrenal levels of MRAP and MC2R in adrenal hyperplasia samples (P < 0.05) but not in tumors. ACTH induced the expression of MRAP 11 ± 2.1-fold and MC2R 20 ± 3.8-fold in all adrenal tissue types (mean ± SEM, both P < 0.0001),whereas AngII augmented these mRNAs 4.0 ± 1.2-fold and 12.6 ± 3.2-fold (P <0.0001) in all but the ACC. MRAP2 expression was suppressed by forskolin (-24 ± 15%, P = 0.013) and PMA (-22 ± 7%, P = 0.0007). MRAP, MRAP2, or MC2R levels were not associated with the induction of cortisol, cAMP, or gene expression by ACTH in vitro. CONCLUSION: MRAP and MC2R expression is induced by ACTH and AngII, which would facilitate cell surface receptor availability. Physiological expression levels of MRAP, MRAP2, and MC2R were not limiting for ACTH sensitivity. PMID: 22419722 [PubMed - indexed for MEDLINE]

Correlation of immunohistochemical staining p63 and TTF-1 with EGFR and K-ras mutational spectrum and diagnostic reproducibility in non small cell lung carcinoma. Thunnissen E, Boers E, Heideman DA, Grünberg K, Kuik DJ, Noorduin A, van Oosterhout M, Pronk D, Seldenrijk C, Sietsma H, Smit EF, van Suylen R, von der Thusen J, Vrugt B, Wiersma A, Witte BI, den Bakker M. Virchows Arch. 2012 Dec;461(6):629-38. For treatment purposes, distinction between squamous cell carcinoma and adenocarcinoma is important. The aim of this study is to examine the diagnostic accuracy on lung cancer small

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biopsies for the distinction between adenocarcinoma and squamous cell carcinoma and relate these to immunohistochemical and KRAS and EGFR mutation analysis. An interobserver study was performed on 110 prospectively collected biopsies obtained by bronchoscopy or transthoracic needle biopsy of patients with non-small cell lung cancer. The diagnosis was correlated with immunohistochemical (IHC) analysis for markers of adeno- (TTF1 and/or mucin positivity) and squamous cell differentiation (P63 and CK5/6) as well as KRAS and EGFR mutation analysis. Eleven observers independently read H&E-stained slides of 110 cases, resulting in a kappa value of 0.55 ± 0.10. The diagnosis non-small cell lung cancer not otherwise specified was given on average on 29.5 % of the biopsies. A high concordance was observed between hematoxylin-eosin-based consensus diagnosis (≥8/11 readings concordant) and IHC markers. In all cases with EGFR (n = 1) and KRAS (n = 20) mutations, adenodifferentiation as determined by IHC was present and p63 staining was absent. In 2 of 25 cases with a consensus diagnosis of squamous cell carcinoma, additional stainings favored adenodifferentation, and a KRAS mutation was present. P63 is most useful for distinction between EGFR/KRAS mutation positive and negative patients. In the diagnostic work-up of non-small cell lung carcinoma the limited reproducibility on small biopsies is optimized with immunohistochemical analysis, resulting in reliable delineation for predictive analysis. PMID: 23064619 [PubMed - indexed for MEDLINE]

Treatment of breast cancer during pregnancy: an observational study. Loibl S, Han SN, von Minckwitz G, Bontenbal M, Ring A, Giermek J, Fehm T, Van Calsteren K, Linn SC, Schlehe B, Gziri MM, Westenend PJ, Müller V, Heyns L, Rack B, Van Calster B, Harbeck N, Lenhard M, Halaska MJ, Kaufmann M, Nekljudova V, Amant F. Lancet Oncol. 2012 Sep;13(9):887-96. BACKGROUND: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child. METHODS: We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833. FINDINGS: From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045).

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Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539). INTERPRETATION: Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance. FUNDING: BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium. PMID: 22902483 [PubMed - indexed for MEDLINE]

Prognostic value of estrogen receptor and progesterone receptor conversion in distant breast cancer metastases. Hoefnagel LD, Moelans CB, Meijer SL, van Slooten HJ, Wesseling P, Wesseling J, Westenend PJ, Bart J, Seldenrijk CA, Nagtegaal ID, Oudejans J, van der Valk P, van Gils CH, van der Wall E, van Diest PJ. Cancer. 2012 Oct 15;118(20):4929-35. BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor α (ERα) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ERα and PR on survival in a large group of distant non-bone breast cancer metastases. METHODS: Receptor conversion was studied by immunohistochemistry in a group of 233 metastatic breast cancer patients. Kaplan-Meier overall survival curves were plotted, and differences between the curves were analyzed by log-rank analysis. The additional prognostic value of conversion to established prognosticators was studied by Cox regression. RESULTS: Overall survival of patients showing conversion from positive to negative ERα or PR, or from negative to positive ERα or PR, or remaining receptor negative was comparable, and significantly worse than patients remaining receptor positive. ERα or PR receptor conversion from positive in the primary breast tumor to negative in distant metastases has independent negative prognostic value. CONCLUSIONS: ERα or PR receptor conversion from positive in the primary breast cancer to negative in distant metastases has negative prognostic value. PMID: 22415862 [PubMed - indexed for MEDLINE]

Yield of routine molecular analyses in colorectal cancer patients ≤70 years to detect underlying Lynch syndrome. van Lier MG, Leenen CH, Wagner A, Ramsoekh D, Dubbink HJ, van den Ouweland AM, Westenend PJ, de Graaf EJ, Wolters LM, Vrijland WW, Kuipers EJ, van Leerdam ME, Steyerberg EW, Dinjens WN; LIMO Study Group. Pathol. 2012 Apr;226(5):764-74.

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Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients ≤70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged ≤50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients ≤70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (≤50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients. PMID: 22081473 [PubMed - indexed for MEDLINE]

Overige publicaties Een man met schildklierafwijkingen. Ectopisch bijschildklieradenoom en multifocaal schildkliercarcinoom. Kwee HW, Marapin V, Verkeyn J, van Nederveen FH. Ned Tijdschr Geneeskd. 2012;156(41):A5146.

Longpathologie, een overzicht van interstitiële longafwijkingen. van Nederveen FH. VAP 2012 , no. 6 (december): 28-31.

Voordrachten Air crash investigation, hoe het begon: werkwijze NFI-pathologie bij luchtvaartongevallen, 1995-2007. van Ingen G. Symposium Werkgroep Forensische Medische Wetenschappen der Lage Landen, 23 november 2012, Antwerpen België.

Pheochromocytoma/paragangliomas: sporadic and inherited. van Nederveen FH. European Society of pathologie, september 2012, Praque Czech Republic.

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SDH immunohistochemistry in the diagnosis of hereditary or multiple endocrine neoplasias. van Nederveen FH. International working group on multiple endocrine neoplasia (IWMEN), september 2012, Liege België.

The differential diagnosis of retinal hemorraghes in shaken baby syndrome. Mooy CM. European Conference on child abuse and neglect 23-25 mei 2012, Amsterdam.

Mucinous eccrine carcinoma of the eyelid. Mooy CM. European Ophthalmic Pathology Society (EOPS),13-16 juni 2012, London, UK.

An update on Intraocular pathology: congenital malformations. Mooy CM. Int. Academy Pathology; 30 september-5 october 2012, Kaapstad, Zuid-Afrika.

Ophthalmic pathology: slide seminar session: Synophthalmia in holoprosencepahly. Mooy CM. Int. Academy Pathology; 30 september-5 october 2012, Kaapstad, Zuid-Afrika.

Promotiecommissie Drs. P. de Graaf : Diagnostic Imaging in Retinoblastoma 5 april 2012. Mooy CM.

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Voordrachten Zwangerschap en psychiatrie: een zorgprogramma. Derksen M. Nascholing “Licht en Donker” voor psychiaters, 26 januari 2012, Zermatt Zwitserland. Geaccrediteerd door de Nederlandse Vereniging voor psychiatrie.

EMDR: de angst voorbij in het ziekenhuis. Derksen M, Baeten B, Horst F. Voorjaarscongres van de Nederlandse Vereniging voor Psychiatrie, 5 april 2012. Geaccrediteerd door de Nederlandse Vereniging voor psychiatrie.

Posters Internal audit as a preparation for an external audit. van de Ridder JMM, Oostenbroek RJ, Derksen M. AMEE ( Association for medical Education in Europe) congres, 27-29 augustus 2012, Lyon France.

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Radiologie

Value of acute-phase reactants in monitoring disease activity and treatment response in idiopathic retroperitoneal fibrosis. Pelkmans LG, Aarnoudse AJ, Hendriksz TR, van Bommel EF. Nephrol Dial Transplant. 2012 Jul;27(7):2819-25. Epub 2012 Jan 23. Background: Prospective evaluation of the value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in monitoring disease activity and treatment response in patients with idiopathic retroperitoneal fibrosis (RPF). Methods: This study included 57 patients with idiopathic RPF receiving tamoxifen monotherapy with at least 8 months follow-up. Clinical, laboratory and radiological investigation was performed at presentation and at repeated follow-up. Remission was defined as significant clinical improvement within 6 weeks of treatment together with stable or decreasing mass size on follow-up computed tomography (CT) scanning at 4 months and definitive decrease in mass size on follow-up CT scanning at 8 months. Results: ESR and CRP levels at presentation and their respective decreases over time correlated strongly with each other (P < 0.001). Baseline ESR and CRP levels correlated with visual analogue scale (VAS) score for pain (ESR, P < 0.01; CRP, P < 0.001); baseline ESR levels also correlated with VAS score for discomfort (P < 0.001). Short-term decreases in ESR or CRP levels at 6 weeks follow-up did not correlate with subsequent mass regression but decrease in ESR at 4 months and decrease in CRP at 4 and 8 months follow-up correlated with mass regression. Kaplan-Meier analysis showed no difference in remission rate between patients with normal or elevated baseline ESR or CRP (log-rank P = 0.22/P = 0.88) or between patients with or without (near-)normalization of ESR or CRP in first 6 weeks of treatment (logrank P = 0.12/P = 0.32). Conclusions: Patients with idiopathic RPF who have elevated acute-phase reactant levels are more symptomatic. Neither acute-phase reactant levels or their initial changes can be taken as a major predictor for treatment success. PMID: 22273666 [PubMed - in process]

Long-term safety and efficacy of a tamoxifen-based treatment strategy for idiopathic retroperitoneal fibrosis. van Bommel EF, Pelkmans LG, van Damme H, Hendriksz TR. Eur J Intern Med. 2012 Dec 12.[Epub ahead of print]

A rare case of massive papillary fibroelastoma of the right ventricular free wall. Baks T, Galema TW, Bakker J, Kofflard MJ. Neth Heart J. 2012 Aug;20(7-8):330-1.

A fatal complication caused by occult pheochromocytoma after splenic artery embolization for malignant hypersplenism. Dinkelaar W, Elgersma O, Levin MD. Cardiovasc Intervent Radiol. 2012 Aug;35(4):971-4.

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PMCID: PMC3396346 PMID: 22190248 [PubMed - in precess]

Long-term safety and efficacy of a tamoxifen-based treatment strategy for idiopathic retroperitoneal fibrosis. van Bommel EFH, Pelkmans LG, van Damme H, Hendriksz TR Eur J Intern Med. 2012 Dec 12.[Epub ahead of print] BACKGROUND: Tamoxifen may be a viable treatment option for idiopathic retroperitoneal fibrosis (iRPF) but data are limited and its long-term safety and efficacy is unclear. We describe the long-term course and outcomes in a large group of patients with iRPF treated with tamoxifen monotherapy. METHODS: This is a single-center prospective, observational study of 55 patients with iRPF treated with tamoxifen for 2years from April 1998 through April 2011. Measurements included clinical improvement, laboratory parameters and follow-up computed tomographic (CT) scanning. Treatment success was the composite endpoint of clinical improvement, mass regression and definite resolution of ureteral obstruction. RESULTS: Forty-seven (85%) patients reported substantial resolution of symptoms after median treatment duration of 3.0weeks (IQR 1.4-4.8weeks). Repeated CT scanning showed mass regression in 39 (71%) patients at 4months and 47 (85%) patients at 8months of follow-up, respectively. Nineteen (34.5%) patients did not meet the composite endpoint of treatment success, 56% of whom responded satisfactorily to second-line immunosuppressive treatment. Recurrence-free survival in patients with treatment success after post-treatment follow-up of 21months (IQR 9.0-35.0months) was 68%. Tamoxifen was well tolerated. Pulmonary embolism occurred in 2 patients receiving tamoxifen and in one patient receiving second-line treatment. CONCLUSION: Tamoxifen is a safe and viable therapeutic option in the treatment of iRPF. PMID: 23246124 [PubMed - as supplied by publisher]

Voordrachten Technical and Clinical Image Quality Comparison of 3 MP and 6 MP LCD Monitors for Radiology. Dams FEM, Kock MCJM, van der Valk PHM, Leung KYE, Niehof SP, Bosman J. 17e Radiologendagen NVvR, 28 september 2012, ’s-Hertogenbosch.

Visceral fat volume and its association with mesenteric panniculitis. Meulman T, van Putte-Katier N, Elgersma O, Hendriksz TR. European Society of Gastrointestinal and Abdominal Radiology, 12-15 Juni 2012, Edinburgh Verenigd Koninkrijk.

Posters Assessment of prognostic LV parameters with CMR in hypertrophic cardiomyopathy: impact of the papillary muscles. Gommans F, Bakker J, Cramer EG, Kurvers MJ, Brouwer MA, Verheugt FW, Kofflard MJM. 15th Annual SCMR Scientific Sessions, Orlando Florida USA, 2-5 February 2012. 81

Radiologie

Technical and Clinical Image Quality Comparison of 3 MP and 6 MP LCD Monitors for Radiology. Dams FEM, Kock MCJM, van der Valk PHM, Leung KYE, Niehof SP, Bosman J. Wetenschapsdag Albert Schweitzer ziekenhuis, 21 juni 2012, Dordrecht.

Epipericardial fat necrosis: A rare cause of pleuritic pain. Luyendijk JM, ter Braak BPM, Schaefer-Prokop CM. European Society of Cardiac Radiology, 25–27 oktober 2012, Barcelona Spanje.

82

Reumatologie

PubMed publicaties Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. de Jong PH, Hazes JM, Barendregt PJ, Huisman M, van Zeben D, van der Lubbe PA, Gerards AH, de Jager MH, de Sonnaville PB, Grillet BA, Luime JJ, Weel AE. Ann Rheum Dis. 2012 Jun 7. [Epub ahead of print] OBJECTIVE: To determine the most effective induction disease-modifying antirheumatic drug (DMARD) strategy in early rheumatoid arthritis (RA), second to compare one single dose of intramuscular glucocorticoids (GCs) with daily oral GCs during the induction phase. METHODS: The 3-month data of a single-blinded clinical trial in patients with recent-onset arthritis (tREACH) were used. Patients were included who had a high probability (>70%) of progressing to persistent arthritis, based on the prediction model of Visser. Patients were randomised into three induction therapy strategies: (A) combination therapy (methotrexate (MTX) + sulfasalazine + hydroxychloroquine) with GCs intramuscularly; (B) combination therapy with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. A total of 281 patients were randomly assigned to strategy (A) (n=91), (B) (n=93) or (C) (n=97). RESULTS: The Disease Activity Score (DAS) after 3 months was lower in patients receiving initial combination therapy than in those receiving MTX monotherapy (0.39 (0.67 to 0.11, 95% CI)). DAS did not differ between the different GC bridging treatments. After 3 months 50% fewer biological agents were prescribed in the combination therapy groups. Although the proportion of patients with medication adjustments differed significantly between the treatment arms, no differences were seen in these adjustments due to adverse events after stratification for drug. CONCLUSION: Triple DMARD induction therapy is better than MTX monotherapy in early RA. Furthermore, no differences were seen in medication adjustments due to adverse events after stratification for drug. Intramuscular and oral GCs are equally effective as bridging treatments and both can be used. PMID: 22679301 [PubMed - as supplied by publisher]

Treatment decisions and related costs differ significantly depending on the choice of a disease activity index in RA, according to 1987 and 2010 classification criteria. de Jong PH, Hazes JM, van Zeben D, van der Lubbe PA, de Jager MH, de Sonnaville PB, Luime JJ, Weel AE. Rheumatology (Oxford). 2012 Jul;51(7):1269-77. Epub 2012 Feb 29. Objective: To evaluate the therapeutic and economic consequences of various disease activity indices (DAIs) in RA according to 1987 and 2010 criteria. Methods: Data on disease activity states from all sustained visits were assessed from all patients who participate in the treatment in the Rotterdam Early Arthritis Cohort (tREACH)

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study, a stratified randomized trial to evaluate different treatment strategies in patients with a symptom duration of <1 year. Frequencies of treatment adaptations, based upon exclusive thresholds of various DAIs, were visualized in reclassification tables. The Stuart-Maxwell test was applied to analyse any significant differences between treatment decisions according to the different DAIs. Simulated annual median medication costs were estimated using the tREACH medication protocol with standard national costs. Results: DAIs perform similar in RA according to 1987 and 2010 criteria. A total of 1104 DASs per DAI were available from 296 patients. DAIs differ significantly, compared with DASs, in classifying a patient’s disease state. Consequently, treatment intensifications occur more frequently with SDAI, CDAI and DAS-28 usage, compared with DAS. Tapering treatment occurs less frequently with SDAI and CDAI and more frequently with DAS-28 usage. Simulated annual median medication costs are significantly higher if DAS-28, SDAI and CDAI are used compared with DAS usage. Conclusion: Usage of various DAIs in a single patient leads to inconsistent disease state categorizations. Consequently, these inconsistencies significantly influence therapeutic decisions and accompanying costs. As DAI usage is imperative to uphold current European League Against Rheumatology (EULAR) treatment recommendations, physicians should consider these therapeutic and economic consequences before choosing a particular DAI. PMID: 22378716 [PubMed - in process]

84

Spoedeisende geneeskunde

Voordrachten The HEART score for chest pain patients at the emergency department validated in a multicentre Asia-Pacific population. Backus BE, Six AJ, Cullen L, Greenslade J, Than M. 6th Dutch North Sea EM Conference, NVSHA Egmond aan Zee Nederland, 30 mei-1 juni 2012 / ICEM, Dublin Ireland, 27-30 juni 2012 / ESC Congres, Munchen Germany, 25-29 augustus 2012.

Posters Hyperextension injury of the cervical spine: no need for imaging? van der Velden AM, Bink MHC, Tempelaars L. 6th Dutch North Sea EM Conference NVSHA, Egmond aan Zee Nederland, 30 mei-1 juni 2012.

Does tracheal intubation with the C-MAC® or Glidescope® videolaryngoscope improve glottic view and successful intubation compared with the Macintosh laryngoscope? van Hooft M. 6th Dutch North Sea EM Conference NVSHA, Egmond aan Zee Nederland, 30 mei-1 juni 2012.

Reduction of medical consumption in low risk chest pain patients. Backus BE, Six AJ, Kingma AEC, Cramer MJM, de Wit GA, Mosterd A, Senden PJ, Mast TP, Doevendans PA. 6th Dutch North Sea EM Conference NVSHA, Egmond aan Zee Nederland 30 mei-1 juni 2012 / Wetenschapsdag ASz 21 juni 2012 / ESC Congres, Munchen Germany, 25-29 augustus 2012.

Is the exercise test valuable for risk evaluation for chest pain after presentation at the emergency department? Backus BE, Six AJ, Poldervaart J, de Beaufort HWL, Cramer MJM, Veldkamp RF, Mast EG, Buys EM, Tietge WJ, Groenemeijer BE, Cozijnsen L, Wardeh AJ, den Ruiter HM, Doevendans PA. 6th Dutch North Sea EM Conference NVSHA, Egmond aan Zee Nederland, 30 mei-1 juni 2012.

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Prognostic factors factors in chest pain patients: a quantative analysis of the HEART score. Backus BE, Six AJ, Doevendans PA, Kelder JC, Steyerberg EW, Vergouwe Y. 6th Dutch North Sea EM Conference NVSHA, Egmond aan Zee Nederland, 30 mei-1 juni 2012 / ESC Congres, Munchen Germany, 25-29 augustus 2012.

The value of clinical and laboratory diagnostics for chest pain patients at the emergency department. Backus BE, Jellema LC, Six AJ, Braam R, Groenemeijer B, van der Zaag H, Tio R, van Suijlen JDE. 6th Dutch North Sea EM Conference NVSHA, Egmond aan Zee Nederland, 30 mei-1 juni 2012.

Emergency physicians as role models - without having had a role model themselves, is that possible? Spruyt C, Dautzenberg B, van de Ridder M. AMEE 2012, Lyon France.

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Urologie

PubMed publicaties Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study. Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, Bjartell A, van der Schoot DK, Cornel EB, Conti GN, Boevé ER, Staerman F, Vis-Maters JJ, Vergunst H, Jaspars JJ, Strölin P, van Muilekom E, Schröder FH, Bangma CH, Roobol MJ. Eur Urol. 2012 Nov 12. [Epub ahead of print] BACKGROUND: Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. OBJECTIVE: To update our experience in the largest worldwide prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS: Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3-6 mo, and volumebased repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. RESULTS AND LIMITATIONS: In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. CONCLUSIONS: Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. TRIAL REGISTRATION: The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718). PMID: 23159452 [PubMed - as supplied by publisher]

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Ziekenhuisapotheek

Overige publicaties De ervaring: Ileostoma en medicijnen; medicijnen bij een stoma vraagt om behandeling op maat. Hiel DCW en Tijssen T (Inhoudelijke bijdrage aan artikel). Vooruitgang 2012, Nederlandse stomavereniging. Juni 2012

Voordrachten Een vergelijkend cohort onderzoek naar de PREValentie van Iatrogene Ziekenhuisopnames op de afdelingen interne geneeskunde / cardiologie / longziekten in een topklinisch opleidingsziekenhuis tussen 2007 en 2011. Hiel DCW. Registratie voordracht CWZO 19 juni 2012. Geaccrediteerd door: Nederlandse Vereniging van Ziekenhuisapothekers.

Weg met de look-alikes. Veenbaas T. Achmea Zorgveiligheid- en Goede Praktijkendag, 23 mei 2012. Geaccrediteerd door: Nederlandsche vereniging van Ziekenhuisapothekers.

Farmacotherapeutische rationale van apotheekbereidingen. Veenbaas T. GMP 3 daagse van Pharmatech, 2 april 2012. Geaccrediteerd door: Nederlandsche vereniging van Ziekenhuisapothekers

Huisflora. Veenbaas T. Cursus organisatie en coördinatie GMP-z Update 2012, 30 oktober 2012. Geaccrediteerd door: Nederlandsche vereniging van Ziekenhuisapothekers.

88

Promoties ASz 2012

Anaesthesie Promotie Cynthia So-Osman op 31 oktober 2012 te Leiden Onderwerp: “Patient Blood Management in Orthopedic Surgery”. Co-promotor: Koopman-van Gemert AWMM.

Chirurgie The Pathogenesis of Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia: A continuing quest. De pathogenese van pulmonale hypoplasie in congenitale hernia diafragmatica: Een voortdurende strijd. Van Loenhout RB. Erasmus Universiteit Rotterdam 30 mei 2012 ISBN: 978-94-6169-256-6

Towards safer liver resections. Leverresecties veiliger uitvoeren. Hoekstra LT. Universiteit van Amsterdam 22 juni 2012 ISBN: 978-90-9026-791-3

Interne geneeskunde Budd-Chiari Syndrome and Portal Vein Trombosis. Etiology and treatment. Etiologie en behandeling van het Budd-Chiari syndroom en vena portae trombose. Smalberg JH. Erasmus Universiteit Rotterdam 12 januari 2012 ISBN: 978-94-6191-144-5

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Promoties ASz 2012

The Influence of Genetic Variation on Van Willebrand Factor Levels and the Risk of Stroke. Van Schie MC. Erasmus Universiteit Rotterdam 9 mei 2012

CIRCULATING TUMOR CELLS counts and characteristics. Circulerende tumorcellen, tellen en typeren. Mostert B. Erasmus Universiteit Rotterdam 21 september 2012 ISBN/EAN: 978-90-9026816-3

Management of Chronic Gastrointestinal Ischemia. De diagnostiek en behandeling van chronische gastrointestinale ischemie. Sana A. Erasmus Universiteit Rotterdam 26 september 2012 ISBN: 978-94-6169-294-8

Longgeneeskunde Promotie Miep van der Drift 12 april 2012 te Nijmegen. Onderwerp: “Epidemiologic and molecular aspects of lung cancer”. Co-promotor: Hol BEA. ISBN: 978-94-6191-205-3

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Wetenschapsdag ASz 2012

91

Wetenschapsdag ASz 2012

Wetenschapsdag ASz 2012

Prijswinnaars In navolging van de call for abstracts zijn er in totaal 22 abstracts ingediend; acht hiervan zijn geselecteerd voor een mondelinge presentatie. Tijdens de Wetenschapsdag heeft de uitgenodigde externe spreker mw. dr. M.A.J. de Ridder van de afdeling biostatistiek van het Erasmus MC, een boeiende presentatie gehouden over “het gevaar van multiple testing”. Na stemming (een publieksstemming) zijn door de voorzitter Wetenschapscommissie de volgende Wetenschapsdagprijzen uitgereikt: De prijs voor de beste voordracht ging na publieksstemming naar Esther Leung (Klinische Fysica) over geluiden van apparaten op de IC. Het publiek verkoos de poster van Ashvin Boeddha (Orthopaedie) over het schrappen van preoperatieve bloedgroepbepalingen ten aanzien van mogelijke bloedtransfusie na totale knieprothese in het Albert Schweitzer ziekenhuis tot beste poster. Prijs voor de beste publicatie 2011 ging naar Ewout-Jan van den Bos (Cardiologie) voor onderzoek naar de betekenis van troponine I stijging bij patiënten met atriumfibrilleren.

92

Mondelinge presentaties

Apotheek Frequency and determinants of correct handling of prescription errors in Dutch hospital pharmacies  M.M. Beex-Oosterhuis¹, E.M. de Vogel¹, P.M.L.A. van den Bemt², I.H. van der Sijs², H.G. Dieleman¹                 ¹Ziekenhuisapotheek Albert Schweitzer Ziekenhuis, Dordrecht ²Ziekenhuisapotheeek Erasmus MC, Rotterdam      Submitted: American Journal of Health System Pharmacy      Publication: PW Wetenschappelijk Platform 2011;33:117-22 Background / Achtergrond Hospital pharmacies combine different strategies for medication surveillance. These strategies are likely to contribute to correct handling of prescription errors, but the exact frequency of correct handling is unknown, as is the contribution of the different strategies to correct handling.  Objective / Doel  To examine the frequency and determinants of correct handling of prescription errors by hospital pharmacies. Methods / Methoden  Prospective observational study with test patients conducted in Dutch hospital pharmacies, using a case-control design to identify determinants of correct handling.       Results / Resultaten 57% Of the prescription errors were handled correctly by the hospital pharmacies (range 7-80%). The use of a computer system was independently associated with correct handling (OR 15.4 (CI95% 3.6-65.5) for computerized physician order entry; OR 15.4 (CI95% 3.6-65.7) for order entry by pharmacy technicians). Furthermore, manual screening of dosages in children with or without computerized surveillance (OR 2.0 (CI95% 1.1-3.8)), qualified pharmacy technicians (OR 1.3 (CI95% 1.0-1.7)) and pharmacy technicians using protocols (OR 1.3 (CI95% 1.0 – 1.6)) were independently associated with correct handling.      Conclusion / Conclusie Handling of prescription errors can be subject to further improvement and the identified determinants can give direction to such improvements.  

93

Mondelinge presentaties

Cardiologie Potential Damage to Early Endothelial Progenitor Cell Mobilization after Percutaneous Coronary Intervention Because of Amplified Mitochondrial Production of Reactive Oxygen Species in White Blood Cells (Preliminary Results) J. van Waardenburg¹, A.J.J. IJsselmuiden¹, J.A. Riedl², M.J.M. Kofflard¹, ¹Afdeling Cardiologie, Albert Schweitzer ziekenhuis ² Afdeling Klinische Chemie, Albert Schweitzer ziekenhuis Background / Achtergrond Studies have shown a role for endothelial progenitor cells (EPCs) in repairing vascular injury post percutaneous coronary intervention (PCI), accelerating re-endothelialization and reducing neointimal hyperplasia. Increased levels of reactive oxygen species (ROS) could impair this EPC function. Objective / Doel To determine the effects of a PCI on mitochondrial and cytosolic ROS and its relation to circulating EPCs in a unselected population of patients admitted for PCI. Methods / Methoden In approximately 25 patients bloodsamples are taken before and within 24h after PCI. After labeling with mito-ROS, CM-DCF, CD33, CD134, CD45 and Anexin the samples are analysed by flowcytometry and in a subpopulation with live-cell microscopy. Results / Resultaten The first 3 patients were used to validate the flowcytometric evaluation of ROS in our center and determine the optimal setting of the fluorescence-activated cell sorter. After these first 3 another group of 3 patients have been evaluated for circulating ROS showing increased preprocedural values when compared to the simultaneously evaluated healthy volunteers, average mean CM-DCF signal intensity of 14,07 vs 6,12 in controls and average mean mito-ROS signal intensity of 18,79 vs 10,31. Following PCI there seems to be a trend towards normalisation of ROS signal intensity, CM-DCF 6,48 and mito-ROS 11,68. This is of course limited by the small sample size of both the patient and the control group. As the EPCprobes had not yet arrived when these first groups were evaluated no data is available of EPC counts around PCI for these first two groups. We expect to have these probes available and validated with the upcoming group of 3 patients. Conclusion / Conclusie Thus far we validated a novel method to determine ROS production after PCI and started to establish a reference base for these values. The first results show a trend towards normalization of previously elevated ROS signal intensity after PCI.

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Interne geneeskunde The implementation of a protocol ‘Weanscreen’ will lead to lower sedation levels, more frequent sedation stops and proper positioning in the ICU H.M. le Grand - den Boer¹, C. Theunisse¹, H.H. Ponssen¹, A.G. van Driel² ¹Department of Intensive Care, Albert Schweitzer hospital ²Department of Quality, Albert Schweitzer hospital Submitted: Programma boek NVIC Intensivistendagen 2012 Background / Achtergrond Literature shows that daily sedation stops and proper use of sedating medication will lead to a reduction of ventilator days, 30 degrees upright position shows in some studies a reduction of the incidence of Ventilated Associated Pneumonia. Objective / Doel The implementation was coordinated by 2 ventilation practitioners and an intensivist. 299 measurements (N= 103) showed that the patient group before and after the implementation were compatible. The ‘after group’ did have a higher APACHE 2 score. Methods / Methoden In the past year every patient was screened in the morning as described in a protocol “weanscreen” : this bundle consisted sedation stops, monitoring delirium CAM-score, 30 degrees upright position, Rapid Shallow Breathing Index ( RSBI ) en spontaneous weaning trials. Results / Resultaten Before implementation 41% of the patients received a sedation stop, this was 70% after implementation.Before implementation 50% of our patients had a 30 degrees upright position, this was 78% after implementation. The depth of sedation (RASS) was significantly reduced: see table 1. Table 1: RASS-score (gem ± s.d.)

Before After -2,9 ± 1,9

-1,2± 1,6

P-value <0,01

Conclusion / Conclusie Implementing a ventilation bundle ‘Weanscreen’ leads to an increase of sedation stops, a reduction of the RASS score and more patients in a 30 degrees upright position.

95

Mondelinge presentaties

Kindergeneeskunde A multidisciplinary training program reduces day and nighttime urinary incontinence in children R.J. Kuppens, G.G.M. van Heesch, T.C.J. Sas, E.D. de Kleijn Afdeling Kindergeneeskunde, Albert Schweitzer Ziekenhuis Background / Achtergrond Urinary incontinence and voiding dysfunction have an incidence up to 20% in 4 to 6 years old children. These symptoms can have a major impact on daily functioning and affect the selfesteem of these children. Objective / Doel To assess the effect of a multidisciplinary therapy program on daytime and nighttime incontinence, according to the terminology of the International Children’s Continence Society. Methods / Methode A baseline controlled, retrospectively study was performed in a one-year cohort of 164 children with voiding dysfunction and urinary incontinence, that underwent an individually adapted training program. The primary outcome was a change in symptom frequency measured by a questionnaire. Results / Resultaten Ninety out of 164 children returned the questionnaire. After treatment, the symptom frequency of daytime incontinence was reduced with 81.1% (95%CI 72.4-89.7%) and 64.8% of the children becomes completely dry during the day. The average decrease of frequency of bedwetting was 74.0% (95%CI 63.7-84.4%) and full response was found in 60.3%. Older children had a significantly better treatment outcome for daytime wetting, compared to the younger. The subgroup with an overactive bladder became less often completely dry. Patients and their parents were satisfied with the results after therapy and treatment process. Conclusion / Conclusie We demonstrate that our multidisciplinary therapy program gives a substantial improvement in symptom frequency and more than 60% of the children becomes completely dry.

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Klinische chemie Een goede bepaling van LDL is cruciaal voor de juiste beslissing in de kliniek L. van der Heul-Nieuwenhuijsen¹, S. Stek¹, G.H.M. Tax², F. Verheijen¹, H.J. Vermeer¹ ¹Geintegreerd Klinisch Chemisch Laboratorium, Albert Schweitzer Ziekenhuis ²Reinier de Graaf Groep, Delft Submitted: In preparation for Clinical Chemistry Background / Achtergrond Hoge levels van LDL cholesterol zijn geassocieerd met verhoogde kans op hart en vaatziekten en familiaire hyperlipemie.Therapie is oa afgestemd op het verlagen van LDL met een streefwaarde van LDL < 2,5 mmol/L. LDL wordt in de meeste Nederlandse laboratoria mbv de Friedewald formule berekend. Objective / Doel Echter de max toelaatbare triglycerideconcentratie voor een betrouwbare LDL varieert aanzienlijk tussen alle laboratoria in NL, namelijk van 2,0 - 9,0 mmol/l. Wij onderzoeken de afkapgrens van triglyceriden waarbij de berekende LDL analytisch te correleren is met een direct gemeten LDL. Methods / Methoden Totaal cholesterol, HDL, LDL en triglyceriden werden gemeten op een Olympus 2700 analyser (Beckman Coulter). We onderzochten 100 patienten met triglyceriden concentratie < 2 mmol/l en 234 patienten met triglyceriden > 2 mmol/l. Direct gemeten LDL werd vergeleken met berekende LDL (Friedewald). Results / Resultaten Wij vonden in onze studie dat LDL berekend door de Friedewald formule al wordt onderschat bij triglyceriden > 2 mmol/l t.o.v. directe gemeten LDL met enzymatisch methode. Het gemiddelde LDL bij een triglyceridewaarde van 2 mmol/l was bij berekening (2,19 mmol/l) al 28% lager dan de directe gemeten LDL (3,06 mmol/l). Bij een triglyceridewaarde van 4 mmol/l was de berekende waarde al 64% lager. Hoe hoger de concentratie van triglyceriden hoe groter de negatieve bias van de Friedewaldformule. Het bepalen van een betrouwbare LDL waarde is van groot belang voor de kliniek, omdat de cardiovasculaire NHG/CBO richtlijn een LDL<2,5 mmol/L aanhoudt als klinische beslisgrens voor het voorschrijven van statines. Opvallend is dat de verscheidene studies waarop deze richtlijn gebaseerd is gebruik hebben gemaakt van verschillende methoden om LDL te bepalen. Wij zijn momenteel bezig om een multicentre studie uit te voeren, waarin we de kwaliteit en vergelijkbaarheid van de LDL bepaling op meerdere platformen willen onderzoeken. Conclusion / Conclusie Bij gebruik van de Friedewaldformule in NL, verschilt de afkapgrens van triglyceriden dusdanig, dat de therapeutische afkapgrens van LDL<2,5 daarmee ook sterk zal variëren. Overduidelijk is, dat discrepanties grote klinische en therapeutische consequenties hebben voor cardiovasculaire patiënten.

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Mondelinge presentaties

Klinische fysica Is the intensive care unit as noisy as it seems to be? K.Y.E. Leung¹, B.I. van den Berg - de Bakker¹, K.A.J.M. Kuenen¹, S.P. Niehof¹, H. Ponssen² ¹Klinische Fysica-Medische Techniek ² Intensive Care Background / Achtergrond Delirium in the intensive care unit (ICU) leads to a longer stay and increased mortality. Patients are exposed to various delirium provoking factors such as medication, illness, pain, light exposure and noise. Reduction of noise could lead to less sleep deprivation and thus better patient outcome. Objective / Doel To map the noise surrounding a patient in the ICU, we have developed a method to measure noise levels and frequencies (high or low tone). In this study, we measured noise of typical medical devices in the ICU (such as infusion pumps, ventilators, and vital signs monitors). Methods / Methoden Noise levels of medical devices and their alarms were recorded for 30 seconds using a microphone in an empty ICU room without external noise interference. The results were analyzed using software and displayed in a noise level-frequency graph. We compared the results to international standards. Results / Resultaten By analyzing the noise level-frequency graph, we were able identify each individual medical device and its alarm. The measured devices without alarms produced noise levels from 40 to 45 dBA. The alarms produced noise levels from 45 to 57dBA.The frequencies of most alarms were between 2 and 8 kHz and could be distinguished from each other in the noise levelfrequency graph. International standards recommend sound level limits from 20 dBA at night to 45 dBA during the day. Conclusion / Conclusie The noise levels of medical devices surrounding the ICU patient are around the international limits during daytime. The noise levels of alarms exceed the limits during day and night. Regarding the adverse effects of noise for patient outcome, the results indicate that sound reduction is recommended.

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Longgeneeskunde Doodsbenauwd leven…. N. de Graaf Verpleegkundig Specialist, poli Longgeneeskunde Background / Achtergrond Dit praktijkonderzoek heeft plaatsgevonden in het kader van de masterthese van de opleiding MANP. Het richt zich op de dagelijkse praktijk van longverpleegkundigen die onvoldoende kennis en instrumenten hebben om angst/depressie bij ernstig COPD te signaleren, behandelen en begeleiden. Objective / Doel Patiënten met ernstig Chronic Obstructive Pulmonary Disease (COPD) hebben vaak een zware ziektelast door hun jarenlange longlijden. Comorbiditeit als angst/depressie heeft enorm invloed op de kwaliteit van leven. Er bestaat onderdiagnostiek, - behandeling en -begeleiding van deze problematiek. Methods / Methoden Er heeft literatuuronderzoek plaatsgevonden naar angst/depressie bij COPD; naar gevalideerde vragenlijsten om dit te signaleren; en naar (niet-) medicamenteuze interventies. Tevens is er middels een vragenlijst analyse gedaan onder 70 patiënten naar de prevalentie en relatie met risicofactoren. Results / Resultaten Onderzoek liet zien dat 44,4% van de doelgroep een verhoogde kans heeft op een vermoedelijke depressieve stoornis; 58,7% op een vermoedelijke angststoornis. Vanuit patiëntenperspectief worden als oorzaken van angstklachten genoemd: continue benauwd zijn; angst om te stikken; angst om te sterven; angst voor de toekomst; in paniek raken; zuurstofafhankelijkheid; alleen zijn. Oorzaken voor depressieve klachten: zuurstofafhankelijkheid; afhankelijk zijn van anderen; niets meer kunnen plannen; alleenstaand; invloed partner; onzekere toekomst. Een landelijke netwerkanalyse liet zien dat longverpleegkundigen onvoldoende kennis/ inzicht hebben in angst/depressieve klachten. Zij geven aan behoefte te hebben aan een hulpmiddel om deze klachten te meten; aan kennis over deze klachten en interventies; en verantwoordelijkheidsafspraken binnen deze zorg. Het resultaat is een zakkaart waarin alle praktische informatie rondom angst/depressieve klachten bij ernstig COPD staat. Oorzaken en risicofactoren zijn beschreven waar longverpleegkundigen op dienen te letten. Tevens wordt uitleg gegeven over de HADS vragenlijst; en wordt een overzicht gegeven van alle (niet)-medicamenteuze interventies. Conclusion / Conclusie De ontwikkelde zakkaart stelt longverpleegkundigen in staat tot het signaleren van angsten depressieve klachten bij patiënten met ernstig COPD en het initiëren van interventies bij deze problematiek, waardoor er een gerichte behandeling en begeleiding van deze patiënten ingezet kan worden.

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Mondelinge presentaties

Radiologie Comparison of CT coronary calcium scores using high-pitch and sequential prospective ECG-triggered computed tomography P. Visser, M.C.J.M. Kock Radiologie Afdeling, Albert Schweitzer ziekenhuis Background / Achtergrond High-pitch ECG-triggered cardiac computed tomography (CT) allows cardiac CT imaging with relatively low radiation dose due to fast scanning. CT coronary calcium score (CTCS) is currently performed by using sequential prospectiveECG-triggered CT at relatively higher radiation dose. Objective / Doel In literature high-pitch CTCS is not validated yet. The aim of this study is to assess the diagnostic performance of high-pitch CTCS for coronary calcifications compared to the currently used technique. Methods / Methoden 29 consecutive patients, with suspected coronary artery disease, underwent ECG-triggered CT using a high-pitch mode and a sequential prospective mode. Both CTCS scans of 27 patients were analysed by using the Agatston calcium scoring for coronary calcifications. Results / Resultaten 27 patients, mean age of 54,3 year, had a mean CT calcium score of 65,30±29,60 and 67,68±27,24 high-pitch CTCS and prospective CTCS, respectively. The mean dose length product was 91 and 133 mgy.cm for high-pitch mode and sequential prospective mode, respectively. There was no significant difference between the CTCS (p=0.716, 95% confidence interval (-15.71;10.94)). Perfect correlation of 0.98 was found between the two protocols. The mean heart rate was 58 bpm. There was no correlation between the difference of high-pitch CTCS and prospective CTCS with heart rate (Pearson correlation -0.074, p=0.714). Conclusion / Conclusie High-pitch CTCS allows good performance of CTCS at significantly lower patient dose.     

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Anesthesiologie Bloedtransfusiebeleid 2004-2009: TOMaat- vs niet -TOMaat-patiënten A.W.M.M. Koopman-van Gemert¹, G. Kuijpers¹, E.W. Mandl² ¹Afdeling Anesthesiologie Albert Schweitzer ziekenhuis ²Afdeling Orthopedie Albert Schweitzer ziekenhuis Background / Achtergrond Van 2004-2009 participeerde het ASz in de TOMaat-studie, een 9-armige MCT die in een RTC het BT- besparende effect van Epo en autotransfusie van opgevangen bloed onderzocht. Niet alle orthopeden deden mee. Dit onderzoek vergelijkt het transfusiebeleid in TOmaat-versus niet-Tomaatpatiënten. Objective / Doel Doel van de studie is te onderzoeken of er een verschil in transfusiebeleid is bij orthopeden die participeerden in de studie versus niet-participerende orthopeden. Methods / Methoden Parallel aan de studie is een database bijgehouden van alle patënten die in de jaren 20042009 een THP- danwel een TPK-operatie ondergingen. Onderzocht is onder andere het transfusiebeleid. In de parallelgroep kreeg iedereen met een Hb< 8,2 mmol/l Epo itt tot de RCT. Results / Resultaten In totaal ondergingen 3059 patiënten een THP- danwel TKP-operatie. Van hen participeerde 957 patiënten in de TOMaat-studie. Bij de niet-TOMaat-patiënten werd geen drain geplaatst. In de TOMaatstudie ontvingen 103 patiënten een bloedtransfusie (10,8%) met gemiddeld 10,9 eenheid EC per persoon. In de niet-TOMaatstudiegroep ontvingen 235 patiënten een bloedtransfusie (11,2%), met gemiddeld 2,1 eenheid EC per persoon. In de Studiegroep werden 96 patiënten ingeloot voor EPO. Een deel van de patiënten met een laag Hb viel in de controlegroep. In de niet-studiegroep kregen alle patiënten met een Hb > 8,2 mmol/l Epo. Dit geeft een vertekend beeld. De invloed hiervan op het BT-beleid wordt tijdens de wetenschapsdag gepresenteerd. Conclusion / Conclusie Er is geen verschil aangetoond in bloedtransfusiebeleid tussen orthopeden die wel of niet aan de TOMaatstudie deelnamen. Echter er is wel een verschil in Epo-beleid. Mogelijk dat dit de resultaten beïnvloedt.

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Poster presentaties

Cardiologie Assessment of a Fast Semi-Quantitative Method of Visual Estimation of Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy D.H.F. Gommans¹, J. Bakker², G.E. Cramer¹, M. Kurvers³, F.W.A. Verheugt¹, M.A. Brouwer¹, M.J.M. Kofflard³ ¹Afdeling Cardiologie, UMC St. Radboud Nijmegen ²Afdeling Radiologie, Albert Schweitzer Ziekenhuis ³ Afdeling Cardiologie, Albert Schweitzer Ziekenhuis Background / Achtergrond In hypertrophic cardiomyopathy (HCM) assessment of late gadolinium enhancement (LGE) with MRI is increasingly important as LGE has been demonstrated to be an adverse prognosticator. A faster method of quantification of LGE is needed. Objective / Doel To assess inter-individual agreement of a previously published fast semi-quantitative method for quantification of LGE for multi-centre studies. Methods / Methoden MRI with LGE was performed. Each segment of the AHA-17-segment model was scored to determine extent of LGE (0=no enhancement, 1=1-25%, 2=26-50%, 3=51-75%, 4=76-100%) by two observers. The score was summed to estimate the extent of LGE. Agreement was assessed by comparison of LGE results. Results / Resultaten 60 HCM patients and 28 HCM mutation carriers were included (mean age: 48.9±15.0 years, 42 males). Agreement on presence and extent of LGE was good (kappa=0.768 and r=0.861, p<.001, respectively). In 10 of 88 subjects (11%) there was disagreement on the presence or absence of LGE: in 8 of these 10 subjects the proportion of LV mass with LGE was scored between 1/68 and 3/68 by the other observer (i.e. <5%). In case LGE was present, a difference in extent was reported in 42/43 patients. However, the difference between observers with respect to extent of LGE was less than 3 points (i.e. <5%) in 75% of subjects (32/43). A difference of >6 points (i.e. >10%) was only seen in 4/43 patients (10%). Conclusion / Conclusie There is good agreement on the presence of LGE. With regard to extent of LGE, only 10% differed substantially. We suggest that in multi-centre studies LGE is analyzed by two observers according to this method with a supervising expert to decide on discrepant readings to speed up the analysis.

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The First Reported Use and Evaluation of a Self-Expanding Stent for the Treatment of a Chronic Total Occlusion of a Coronary Artery J. van Waardenburg¹, A.J.J. IJsselmuiden¹, K. Kulekci² ¹Afdeling Cardiologie, Albert Schweitzer ziekenhuis ²Afdeling Cardiologie, Rivas Zorggroep, Beatrixziekenhuis Background / Achtergrond Studies have shown that treatment of a chronic total occlusion (CTO) improves clinical outcome. The optimal treatment of this type of lesion however remains unclear. It is hypothesized that the vessel after revascularization adapts to the restoration of coronary flow and can increase in diameter. Objective / Doel To evaluate the use of a self-expanding stent (STENTYS) for the treatment of a CTO and investigate the adaptive capacity of the coronary vessel to the restoration of coronary flow in a preliminary explorative study. Methods / Methode After the succesfull treatment of a CTO with a STENTYS stent the vessel was evaluated by optical coherence tomography (OCT) both distal of the treated segment as well as the stented segment. This evaluation was repeated 7 days after the initial procedure. Results / Resultaten OCT at baseline and after 7 days showed an increase in mean lumen diameter (MLD) of approximately 4% and an increase of approximately 8% in mean lumen area (MLA) distal of the stented segment. In the stented part of the vessel an increase was shown of 6.8% for the MLD and of 14.0% for the MLA. The stent itself increased 17.9% in mean stent diameter (MSD) and 38.7% in mean stent area (MSA). The difference between lumen and stent diameter values was caused by the intimal covering of the stent and possibly some (temporary) intimal thickening. Conclusion / Conclusie This is the first reported evidence of a 14% increase in MLD in the treated segment of a CTO, this growth is followed by the adaptive capacities of the STENTYS stent. A further study evaluating the treatment of this type of lesions with a self-expandable stent is being developed in our center.

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Poster presentaties

Chirurgie “The “I-aid”: a new care pathway to improve quality of care and quality of life in ileostomy and colostomy patients” M.F. Sier¹, D.T. Ubbink², J.G. Huis in het Veld², G.J. Veldink³, R.J. Oostenbroek¹, W.A. Bemelman4 ¹Afdeling Heelkunde, Albert Schweitzer ziekenhuis ²Afdeling kwaliteit en proces innovatie, AMC ³Afdeling stomapoli, AMC 4Afdeling heelkunde, AMC Background / Achtergrond Three quarters of the Dutch patients with an ostomy report serious limitations at social, sexual, and physical levels. About half of these patients have had a stoma-related complication. 25% of them complain about a lack of knowledge, skills, and education by the caregivers. Objective / Doel To provide evidence whether a different perioperative care pathway, including home visits, for patients requiring an ileo- or colostomy reduces complication rates and improves quality of life against acceptable costs. Methods / Methoden Fifteen-centre cluster randomised clinical study (“I-aid” study) with a stepped wedge design (Brown 2006). We plan to compare the costs and effectiveness of a different, uniform ostomy care pathway vs. the current pathway to improve the quality of care and quality of life of patients. Results / Resultaten The new stoma care pathway will offer a more elaborate instruction and closer monitoring programme in the perioperative and outpatient phases, mainly performed by the stoma care nurses. Our recent pilot study indicated that additional postoperative home visits by stoma care nurses help improve stoma care and avoid complications. After the 24-month “I-aid” trial, we hope this new care pathway leads to a reduction in the number of stoma-related complications and a better quality of life at acceptable costs, as compared with the standard perioperative care for ostomate patients. Conclusion / Conclusie Because the incidence of stoma-related complications is high, there is room for improvement. The upcoming trial is an attempt to reduce such complications and to improve the quality of care for ostomy patients.

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Interne geneeskunde Value of acute-phase reactants in monitoring disease activity and treatment response in idiopathic retroperitoneal fibrosis L.G. Pelkmans¹, A.L.H.J. Aarnoudse¹, T.R. Hendriksz², E.F.H. Van Bommel¹ ¹Afdeling Interne geneeskunde, Albert Schweitzer ziekenhuis ²Afdeling Radiologie, Albert Schweitzer ziekenhuis Submitted: Nephrology Dialysis Transplantation Reference: Nephrol Dial Transplant. 2012 Jan 23 Background / Achtergrond Retroperitoneal fibrosis (RPF) is a rare inflammatory collagen vascular disease, typically surrounding abdominal aorta and iliac arteries. Elevated acute-phase reactant levels are thought to represent active inflammation and hence, indicative of a potential response to medical treatment. Objective / Doel Prospective evaluation of the value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in monitoring disease activity and treatment response in patients with idiopathic retroperitoneal fibrosis (RPF). Methods / Methoden 57 patients with iRPF receiving tamoxifen monotherapy with at least 8 months follow-up. Clinical, laboratory and radiological investigation was performed at presentation and at repeated follow-up.   Results / Resultaten ESR and CRP levels at presentation and their respective decreases over time correlated strongly with each other (P <0.001). Baseline ESR and CRP levels correlated with visual analogue scale (VAS) score for pain (ESR, P < 0.01; CRP, P < 0.001); baseline ESR levels also correlated with VAS score for discomfort (P < 0.001). Short-term decreases in ESR or CRP levels at 6 weeks follow-up did not correlate with subsequent mass regression but decrease in ESR at 4 months and decrease in CRP at 4 and 8 months follow-up correlated with mass regression. Kaplan-Meier analysis showed no difference in remission rate between patients with normal or elevated baseline ESR or CRP (log-rank P = 0.22/P = 0.88) or between patients with or without (near-)normalization of ESR or CRP in first 6 weeks of treatment (log-rank P = 0.12/ P = 0.32). Conclusion / Conclusie Patients with iRPF who have elevated acute-phase reactant levels are more symptomatic. Acute-phase reactant levels nor their initial changes can be taken as a major predictor for treatment success.

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Poster presentaties

Kindergeneeskunde Maternaal SSRI gebruik in de zwangerschap, postpartum beleid in Nederland bij de pasgeborene J.E. Wakker – Deelen, A.V.N. Schmetz, A.C. de Mol Afdeling kindergeneeskunde, Albert Schweitzer ziekenhuis Background / Achtergrond Pasgeborenen na maternaal Selective Serotonine Re-uptake Inhibitor SSRI gebruik in de zwangerschap vormen een grote groep kinderen. De juiste zorg voor deze kinderen is onduidelijk en (inter)nationaal is het postnatale beleid waarschijnlijk sterk verschillend, maar nooit goed in kaart gebracht. Objective / Doel Inzichtelijk maken van de verschillen in beleid in de Nederlandse ziekenhuizen met betrekking tot a terme neonaten die geboren zijn na maternaal SSRI-gebruik tijdens de zwangerschap. Tevens bevindingen beschrijven van 48 uur standaard monitoring en glucosecontroles van een 1-jaars pilotcohort. Methods / Methode Enquete onderzoek onder Nederlandse ziekenhuizen (n=96) om inzicht te krijgen in het gevoerde beleid. Tevens werd het nut van standaard 48 uur monitor bewaking en glucosecontroles onderzocht in een prospectieve cohort studie bij a terme neonaten na maternaal SSRI gebruik. Results / Resultaten Responspercentage van de enquête bedraagt 79% (n=76). In 96% van de responderende ziekenhuizen vindt standaard observatie plaats. In 77% betreft dit de kraamafdeling, in 23% de afdeling neonatologie icm monitorbewaking. De opnameduur varieert, waarbij een meerderheid van de centra 48 uur aanhoudt. Glucosecontroles worden in 12% van de ziekenhuizen standaard verricht. Een derde van de ziekenhuizen ziet de kinderen poliklinisch terug. Meerdere klinieken zijn van plan dit in de toekomst te gaan doen. Controle wordt in een aantal ziekenhuizen samen met de psychiater verricht. Tijdens de observaties binnen het cohort blijkt dat indien er in de eerste 24 uur geen incidenten plaatsvinden, deze ook niet voorkomen in het volgende etmaal. Glucosecontroles laten geen afwijkingen zien. Conclusion / Conclusie Evidente verschillen in beleid in Nederland zijn inzichtelijk gemaakt. Monitorbewaking langer dan 24 uur lijkt niet zinvol indien in deze periode geen incidenten hebben plaatsgevonden. Standaard glucosecontroles lijken niet noodzakelijk. Deze data dienen bevestigd te worden in een groter cohort.

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Klinische fysica Dosisreductie door directe dosis feedback bij interventies   J. Bosman, E. van Schrojenstein Lantman, E. Leung Afdeling klinische fysica - medische techniek Background / Achtergrond Personeel ontvangt tijdens radiologisch geleide procedures een hoeveelheid stralingsdosis. Met behulp van een nieuwe dosimeter kan d.m.v directe feedback de specialist inzicht krijgen in de dosis die hij ontvangt en direct maatregelen nemen om zijn/haar dosis omlaag te brengen.   Objective / Doel Presentatie van de eerste resultaten van de metingen zoals die zijn uitgevoerd in de cathkamer. Methods / Methoden De eerste metingen van persoonsdosis zijn op de cathkamer zonder en met feedback uitgevoerd. Een vergelijking is gemaakt met de standaard badge die het personeel draagt. Results / Resultaten De metingen zijn nog gaande. De eerste resultaten worden in april verwacht Conclusion / Conclusie De metingen zijn nog gaande. De resultaten worden in april verwacht

Kwaliteit, veiligheid & innovatie Het Albert Schweitzer ziekenhuis: een aantrekkelijke werkplek voor verpleegkundigen? C.J. Figaroa-Fingal Afdeling Kwaliteit, Veiligheid & Innovatie Background / Achtergrond Door grote tekorten aan verpleegkundig personeel is sinds de jaren ‘80 in de V.S. wetenschapelijk onderzoek verricht naar ziekenhuizen die erg aantrekkelijk zijn voor verpleegkundigen om in te werken, de zogenaamde Magneet Ziekenhuizen. De kwaliteit van zorg en de arbeidstevredenheid is er beter. Objective / Doel Deze case-study geeft inzicht over de mate van aanwezigheid van de 8 essentiele kenmerken voor een aantrekkelijke werkomgeving onder de verpleegkundigen binnen het ASz, vergeleken met de SANTEON ziekenhuizen in Nederland (participanten pilot Excellente Zorg vanuit de V&VN).

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Poster presentaties

Methods / Methoden In maart 2012 hebben alle gediplomeerde verpleegkundigen binnen het ASz een digitale enquete ontvangen met de Nederlandse “Essentials of Magnetism II” vragenlijst. Afdelingen met een respons groter dan 30% en/of 5 respondenten en meer werden geincludeerd: 20 afdelingen en 259 verpleegkundigen. Results / Resultaten Van de 259 respondenten is het gemiddelde voor het gehele ASz genomen. Bij de volgende essentiele kenmerken van professionele verpleegkundige werkomgeving was er geen significant verschil te zien, vergeleken met de SANTEON ziekenhuizen: (1) Autonomie binnen verpleegkundige werkomgeving (p=0,290), (2) werken met vakbekwame collega’s (p=0,158), (3) opleidingsmogelijkheden (p=0,070) en (4) voldoende gekwalificeerd personeel (p=0,631). Wel is er een significant verschil (p<0,001) te zien bij (5) de professionele relatie tussen de verpleegkundigen en artsen, (6) de ondersteuning vanuit de leidinggevende en (7) de patientgerichte zorgcultuur. Het ASz scoorde op deze essentiele kenmerken voor een aantrekkelijk werkomgeving voor de verpleegkundigen lager dan de SANTEON ziekenhuizen. In (8) zeggenschap over de verpleegkundige werkomgeving scoort het ASz juist significant beter dan de SANTEON ziekenhuizen. Aan het eind van de streep scoorde het ASz significant lager op de totale professionele arbeidstevredenheid bij de verpleegkundigen, als resultaat variabele, vergeleken met de SANTEON ziekenhuizen. Conclusion / Conclusie Verwacht wordt dat zorginstellingen, waarin de 8 kenmerken van een aantrekkelijke werkomgeving aanwezig zijn, beter in staat zijn om hun verpleegkundigen te werven en behouden en dat zij betere kwaliteit van zorg leveren. Deze studie laat de juiste focus voor verbetering zien binnen het ASz.      * Met dank aan B. de Brouwer, MSc, van de V&VN.

Leerhuis Residents’ perceptions of assessment and feedback in a Surgical Department: supervisors must do better! RJ Oostenbroek¹, PW Plaisier², JMM van de Ridder¹ ¹Department of Education, Albert Schweitzer hospital ²Department of Surgery, Albert Schweitzer hospital Background / Achtergrond Assessment of and feedback on performance are very important in the residents´ learning process. However, little is known about how residents perceive their supervisor’s assessment and feedback skills. Objective / Doel We studied how supervisors’ skills and the learning climate were perceived by surgical residents.The Dutch Residents Educational Climate Test (D-RECT) and Systematic Evaluation of Teaching Qualities (SET-Q) are currently used to answer these questions.

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Methods / Methoden Surgical residents filled out the D-RECT in 2009 (n=19), and both the D-RECT and SET-Q in 2010 (n=13) and 2011 (n= 14). Scales scores (Likert 1-5) were determined. In October we will receive the results of 2011. Results / Resultaten In 2009 and 2010 the quality of coaching and assessment (M=3.1 and M=2.9) and feedback (M=3.2 and M=3.0) were the lowest rated aspects of learning climate. However, residents valued supervisors feedback skills (M=3.8) and their assessment skills (M=3.5) as reasonable high. Setting goals together with residents based on assessment needs attention (M=2.8). Conclusion / Conclusie Although residents perceive supervisors’ feedback and assessment skills as reasonably good, actual feedback and assessment are perceived as the weakest part of the learning climate. The perceived discrepancy between supervisors´ feedback and assessment skills and actual feedback needs more attention.

Longgeneeskunde Luchtbevochtiging bij zuurstoftoediening W. Minderhoud Longverpleegkundige, poli Longgeneeskunde en verpleegafdeling C1 Background / Achtergrond Onderzoek is gedaan in het kader van de opleiding tot longverpleegkundige. Als eerste is literatuuronderzoek gedaan. Omdat beschikbare onderzoeksresultaten niet recent zijn, zijn de effecten van het wel en niet bevochtigen in de praktijk onderzocht onder patiënten, opgenomen op de longafdeling. Objective / Doel Er is landelijk geen eenduidig beleid voor luchtbevochtiging bij zuurstoftoediening. In het protocol van ons ziekenhuis staat dat het gebruik van een bevochtiger noodzakelijk is vanaf 5 liter per minuut. In de praktijk wordt de zuurstof echter ook bevochtigd bij minder dan 5 liter per minuut. Methods / Methoden Literatuuronderzoek heeft plaatsgevonden in verschillende Databases. Het praktijkonderzoek heeft plaatsgevonden onder 40 patiënten op afd. C1. Aan de hand van een vragenlijst werden patiënten gericht bevraagd over de effecten van de zuurstoftoediening, eerst 20 met en daarna 20 zonder bevochtiger. Results / Resultaten De literatuurstudie biedt voldoende gronden om zuurstofbevochtiging niet in alle situaties toe te passen. Het bevochtigen van de zuurstof met behulp van een aquapack lijkt nauwelijks tot geen toegevoegde waarde te hebben bij het verlichten van symptomen of klachten die,

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Poster presentaties

meestal tijdelijk, gepaard gaan met het toedienen van zuurstof. Daarnaast heeft het bevochtigen geen invloed op het beoogde effect bij zuurstoftoediening. Volgens de richtlijn van het CBO (2000) leidt het bevochtigen van zuurstof tot een verhoging van de kosten, kan het leiden tot zuurstofverlies en een bron van infecties vormen. Op basis van het praktijkonderzoek kan worden vastgesteld dat het wel of niet bevochtigen van de zuurstof door middel van een aquapack weinig invloed lijkt te hebben op het ervaren van discomfort door patiënt. Conclusion / Conclusie Aanbevelingen: - Zuurstof slechts bevochtigen met behulp van een aquapack vanaf 5 liter per minuut. - Eventueel een uitgebreider onderzoek doen onder een grotere groep patiënten om de effecten op langere termijn te onderzoeken.

Een uitweg uit de neerwaartse spiraal: Ontwikkeling en implementatie van een actieplan ter bevordering van het herkennen en behandelen van een exacerbatie COPD P.S.M. Jordens-Olislagers Background / Achtergrond Dit ontwerpproject is geschreven in het kader van het afstuderen aan de opleiding Master Advanced Nursing Practice aan de Hoge School Utrecht. Het ontwerpproject is een praktijkonderzoek, gericht op het ontwikkelen van interventie om de gevolgen van exacerbaties van patienten met copd te beperken. Objective / Doel Patiënten met Chronische Obstructive Pulmonary Disease maken gemiddeld twee maal per jaar een excerbatie door. Ten gevolge van deze exacerbaties gaat de longfunctie, conditie en de kwaliteit van leven achteruit. Methods / Methoden Voor het praktijkonderzoek is dossier onderzoek gedaan en zijn interviews met patiënten en zorgverleners afgenomen om de probleemstelling goed in beeld te krijgen. Vervolgens is literatuur onderzoek en benchmark onderzoek verricht om de best mogelijk interventie voor de probleemstelling te vinden. Results / Resultaten De uitkomsten van dit onderzoek zijn dat zowel een actieplan als telemonitoring en het gebruik van de CCQ-lijst bijdraagt aan het vroegtijdig herkennen van symptomen van een exacerbatie. In het literatuuronderzoek is een trend zichtbaar dat een actieplan de achteruitgang van kwaliteit van leven beperkt. De resultaten zijn echter niet significant. De respondenten van het benchmarkonderzoek bevestigen deze trend en geven aan wel degelijk de indruk te hebben dat een actieplan positief effect heeft op de kwaliteit van leven van patiënten. Naar effecten van de interventie telemonitoring bij COPD is nog geen gerandomiseerd onderzoek met een controle groep gedaan. Het bewijs van de uitkomsten is van een lager niveau dan van het actieplan.De ervaringen uit het benchmarkonderzoek over telezorg zijn positief. Het vergroot de kennis omtrent ziekte inzicht en het vergroot het vertrouwen van de patiënt.

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De CCQ-vragenlijst is een lijst die ingezet kan worden om zicht te krijgen niet gerapporteerde exacerbaties. Conclusion / Conclusie Gekozen is voor het gebruik van een actieplan met begeleiding van een longverpleegkundige. De infrastructuur voor zelfmanagement, contacten tussen eerste en tweede lijn zijn aanwezig. Dit zijn belangrijke voorwaarden zijn om de interventie succesvol te laten zijn.

Orthopaedie Schrappen van preoperatieve bloedgroepbepalingen ten aanzien van mogelijke bloedtransfusie na totale knieprothese in het Albert Schweitzer Ziekenhuis. AV Boeddha¹, AJ van Koeveringe¹, W van Gelder², LTM Breimer³ ¹Afdeling orthopaedie, Albert Schweitzer ziekenhuis ²Klinisch chemicus, Albert Schweitzer ziekenhuis ³Anesthesiologe, Albert Schweitzer ziekenhuis Background / Achtergrond Een veel toegepaste chirurgische behandeling van invaliderende knieartrose is de plaatsing van een totale knieprothese (TKA). Op dit moment worden er In het ASz bij elke patiënt vooraf aan deze operatie op 2 momenten type&screen (T&S) bloedbepalingen gedaan, in het kader van mogelijke bloedtransfusie per- of postoperatief. Objective / Doel Doel van deze studie was na te gaan of de preoperatieve T&S bepalingen daadwerkelijk noodzakelijk zijn bij patiënten die electief een primaire TKA ondergaan, op basis van het voorkomen van per- en postoperatieve transfusiebehoefte. Methods / Methoden Er werd een retrospectief cohortonderzoek uitgevoerd. Alle patiënten die tussen 1 januari 2010 en 31 december 2011 in het ASz electief een TKA ondergingen, werden geïncludeerd. De patiënten die een bloedtransfusie hebben ondergaan, werden nader geanalyseerd. Results / Resultaten In totaal vonden er 769 TKA’s plaats in bovenstaande periode die allen werden geïncludeerd. Hiervan hebben er 34 patiënten per- of postoperatief een bloedtransfusie ondergaan (4,4%). In onze onderzoekspopulatie vond bij 32 van de 34 patiënten de transfusie minimaal één dag na de operatie plaats; dit was nooit in een acute spoedsituatie. De resterende 2 patiënten werden peroperatief getransfundeerd met een preoperatief Hb van 5.0 en 6.3. Opvallend was dat er bij 8 patiënten asymptomatische anemieën zijn behandeld met een bloedtransfusie. Er hebben bij 24 patiënten (3,1%) symptomatische postoperatieve transfusies plaatsgevonden. Van alle 34 patiënten bleek er steeds sprake van een milde anemie met Hb-waarden schommelend tussen 4.3 en 5.8 waarop er is getransfundeerd. Het preoperatieve Hb was bij 2 patiënten lager dan 6.5 en bij de resterende 32 patiënten hoger dan 6.5. Er is in onze onderzoekspopulatie aan 35 patiënten met een preoperatief laag

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Hb Eprex of Binocrit toegediend; 3 van deze 35 patiënten bleken ondanks Eprex of Binocrit toch postoperatief transfusiebehoeftig te zijn. Conclusion / Conclusie Op basis van het voorkomen van per- en postoperatieve bloedtransfusies blijkt het niet noodzakelijk om de T&S bepalingen al preoperatief te hebben gedaan bij een primaire TKA. Indien er toch een transfusie dient plaats te vinden, is er genoeg tijd om de bepalingen alsnog te doen. Dit is patiëntvriendelijker, kostenbesparend en geheel passend in de ideologie van het Rapid Recovery Programme.

Radiologie Technical and clinical image quality comparison of 3-megapixel and 6-megapixel liquid crystal display (LCD) monitors for radiology F.E.M. Dams¹, K.Y.E. Leung²², S.P. Niehof, P.H.M. van der Valk¹, J. Bosman² ¹Afdeling Radiologie, Albert Schweitzer ziekenhuis ²Afdeling Klinische fysica - Medische techniek, Albert Schweitzer ziekenhuis Background / Achtergrond Since costs of liquid crystal display (LCD) monitors vary considerably among different manufacturers, we performed an objective comparison between displays of three major manufacturers to make a cost-effective decision in replacing all diagnostic displays at our Radiology department. Objective / Doel We performed a technical and clinical comparison between three 3-megapixel (3 MP) displays, Barco, Eizo and NEC, and a Barco 6-megapixel (6 MP) display to establish if there is a significant difference in image quality. Methods / Methoden The names of the manufactures were shielded. Technical and clinical assessment was performed using criteria proposed by the American Association for Physicists in Medicine (AAPM). For clinical assessment statistical analysis was performed using repeated measures analysis of variance (ANOVA). Results /Resultaten The Barco 3 MP display passed all acceptance criteria. The Eizo and NEC displays passed the acceptance criteria, except for the darkest pixel-value in the grayscale display function. The Barco 6 MP failed criteria for maximum luminance response and veiling glare. Clinical assessment outcomes were 7.8 ± 1.1 (Barco 3 MP), 7.8 ± 1.2 (Eizo), 8.1 ± 1.0 (NEC) and 8.1 ± 1.0 (Barco 6 MP) using an scale from 0 to 10. No statistically significant differences were found. Conclusion / Conclusie According to the tested criteria the displays have comparable technical and clinical image

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quality, if calibrated properly. In the purchase of new displays financial aspects should also be taken into consideration.

Spoedeisende hulp Reduction of medical consumption in low risk chest pain patients BE Backus1, AJ Six2, AEC Kingma1, MJM Cramer1, GA de Wit3, A Mosterd4, PJ Senden4, TP Mast1, PA Doevendans1 University Medical Center, Utrecht, The Netherlands

1

Zuwe Hofpoort Hospital, Woerden, The Netherlands

2

Julius Center, Utrecht, The Netherlands

3

Meander medical Center, Amersfoort, The Netherlands

4

Background / Achtergrond Patients with chest pain are often admitted for clinical observation, and treated as ACS awaiting final diagnosis. Consequently, unnecessary diagnostics and treatment are common. The HEART score serves the making of a quick diagnosis and consists of five elements: History, ECG, Age, Risk factors and Troponin. Accurate risk stratification of chest pain patients in the emergency department (ED) by means of the HEART score may help to identify low risk patients, defined by HEART score ≤3, who do not need additional work-up or hospitalization. Methods / Methoden This study was performed in 280 patients in three hospitals in the Netherlands. These patients were participants of a prospective validation study of the HEART score in 2388 chest pain patients in the ED of ten hospitals. Numbers of hospitalization days, exercise tests, echocardiography and various other cardiology examinations were counted. Results / Resultaten Chest pain patients visiting the ED were classified as low-risk, based on the HEART score, in 102/280 (36.5%) of the cases. MACE did not occur in these 102 patients; the risk of MACE was 15/870 (1.7%) in the low HEART score group of the entire prospective study. Eighteen patients (17.6%) were hospitalized for a total of 28 days and additional cardiology work-up was done in 52 patients (51%). Numbers of examinations were: 27 (26.5%) exercise tests, 16 (15.7%) echocardiograms, 5 (5%) CT scans and 6 (5.9%) SPECT. Conclusion / Conclusie When a policy would be made to withhold redundant medicine in low-risk chest pain patients, with a HEART score ≤3, hospitalizations would be saved in one fifth and various examinations in half of the patients. Improved risk stratification in chest pain patients may result in a reduction of medical consumption.

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Verantwoording

De data ten behoeve van het wetenschappelijk jaaroverzicht 2012 zijn verzameld via de leden van de Wetenschapscommissie en via de vakgroepen. Daarnaast is er door het DB Wetenschapscommissie actief gezocht in Google Scholar en PubMed. In het wetenschappelijk jaaroverzicht zijn de publicaties opgenomen die zijn terug te vinden op PubMed. PubMed Publications die al “collaborative authorship” gepubliceerd staan, zijn apart onder PubMed publicaties vermeld onder “PubMed collaborative authorship publicaties. Onder ‘overige publicaties’ zijn internationale/nationale publicaties opgenomen die niet in PubMed zijn terug te vinden en verschenen zijn in tijdschriften die geen impactfactor hebben. Naast PubMed publicaties zijn wetenschappelijke bijdrages in de vorm van een ‘boek of hoofdstuk van een boek’ opgenomen. Voor de genoemde publicaties geldt dat de (co) auteur en tijde van dataverzameling, dataverwerking of opschrijven van de resultaten een aanzienlijk deel van de werkzaamheden moet hebben verricht in het Albert Schweitzer ziekenhuis en daar werkzaam moet zijn (geweest). Het ASz dient dan ook bij de affiliatie vermeld te staan. Indien het artikel van de (co) auteur gepubliceerd wordt tijdens de aanstellingsperiode in het Albert Schweitzer ziekenhuis, maar de feitelijke werkzaamheden reeds onder een andere aanstelling zijn verricht, kunnen de artikelen niet in het Wetenschappelijk Jaaroverzicht van het Albert Schweitzer ziekenhuis worden opgenomen. De digitale publicaties voorafgaand aan de geprinte versie (Epub ahead of print) van 2012 zijn zoveel als mogelijk meegenomen in het jaaroverzicht 2012. Voor ‘voordrachten’ en ‘posters’ geldt dat deze in het wetenschappelijk jaaroverzicht opgenomen worden indien het geaccrediteerde wetenschappelijke symposia, congressen nationaal of internationaal betreft waar een abstract is gepubliceerd. Hierbij geldt dat de (co) auteur ten tijde van de voordracht werkzaam moet zijn (geweest) in het Albert Schweitzer ziekenhuis. Het wetenschappelijk jaaroverzicht is opgesteld volgens de regels voor biomedische tijdschriften, de Vancouverregels. De auteursnamen zijn alfabetisch gerangschikt op naam van de eerste betrokken auteur werkzaam in het Albert Schweitzer ziekenhuis en zijn vet gedrukt. Bij meerdere ASz auteurs is de referentie bij de betreffende vakgroepen opgenomen. De gehele lijst wordt zoveel mogelijk met links naar full text te zijner tijd geplaatst op de intranet - en internetsite van het Leerhuis/ Wetenschapscommissie.

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Dit boek is een uitgave van het Albert Schweitzer ziekenhuis (ASz). Redactie: Claudia C.N. van Waardhuizen, MSc Esther de Kruyf, Secretariaat Leerhuis Dit boek is een initiatief van Albert Schweitzer ziekenhuis Afdeling Leerhuis Postbus 444 3300 AK Dordrecht www.asz.nl Concept en ontwerp: Elan Strategie en Creatie, Rijswijk De redactie aanvaardt geen enkele aansprakelijkheid uit welke hoofde dan ook voor het gebruik van de in de publicatie vermelde resultaten en het toepassen van de daarin beschreven informatie. Een ieder is en blijft hiervoor zelf aansprakelijk, evenals voor de aanlevering van gegevens om het Wetenschappelijk Jaaroverzicht tot stand te brengen. juni 2013

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