Wetenschappelijk overzicht

Transcription

1 Wetenschappelijk overzicht

2 1 Deventer, maart 2014

3 Inhoud Voorwoord Voorwoord 3 Deventer Ziekenhuis 5 Anesthesiologie 6 Cardiologie 7 Dermatologie 24 Gynaecologie 29 Heelkunde 50 Interne Geneeskunde 71 Kaakchirurgie 86 Keel Neus Oorheelkunde 87 Kindergeneeskunde 88 Klinische Chemie 91 Klinische Pathologie 94 Klinische Psychologie 96 Longziekten 102 Maag Darm en Leverziekten 104 Microbiologie 113 Neurologie 120 Oogheelkunde 122 Opleidingsinstituut 125 Orthopedie 126 Radiologie 132 Spoedeisende Hulp 137 Ziekenhuisfarmacie 138 Ziekenhuishygiëne 154 Radiotherapeutisch Instituut Stedendriehoek en Omstreken (RISO) 155 Wetenschapsprijzen State of the Art Lectures Impact Factors 169 Auteurs index 171 Voor u ligt het wetenschappelijk jaaroverzicht van het Deventer Ziekenhuis en het Radiotherapeutisch Instituut Stedendriehoek en Omstreken (RISO). Het Deventer Ziekenhuis is onderdeel van de Samenwerkende Topklinische OpleidingsZiekenhuizen (STZ). Naast opleiden en topklinische functies, is wetenschappelijk onderzoek een belangrijk speerpunt van STZ-ziekenhuizen. Ook het RISO hecht waarde aan het opzetten van en deelnemen aan wetenschappelijk onderzoek. Om als zorginstelling mee te gaan in ontwikkelingen en om een aantrekkelijke werkomgeving te zijn voor professionals, is het uitvoeren van klinisch wetenschappelijk onderzoek van wezenlijk belang. De afgelopen jaren is er binnen het Deventer Ziekenhuis al geïnvesteerd in het bevorderen van onderzoek, wat ertoe bijgedragen heeft dat er een goede basis ligt voor het faciliteren van klinisch wetenschappelijk onderzoek. Dit uit zich in verscheidene wetenschappelijk activiteiten: van het begeleiden van co-assistenten bij hun wetenschappelijke stage, tot het deelnemen aan grootschalige multicenter onderzoeken. Deze verschillende activiteiten zijn weergegeven in dit boek, per vakgebied onderverdeeld in de onderdelen publicaties (als co-auteur in PubMed geïndexeerd), collaborations (als collaborator in PubMed geïndexeerd), voordrachten, posters en promoties. Van de ongeveer 30 specialismen in DZ, zijn er 22 specialismen waarbij in de jaren 2012 en 2013 wetenschappelijk activiteiten hebben plaatsgevonden. De top vier van specialismen met de meeste publicaties wordt gevormd door heelkunde, gynaecologie, ziekenhuisfarmacie en cardiologie. Publicaties geproduceerd vanuit de cardiologie, gynaecologie en MDL zijn gepubliceerd in de bladen met de hoogste impact factor. Het wetenschappelijk werk in het RISO in 2012 en 2013 vertaalt zich in 8 gepubliceerde artikelen met een gemiddelde impact factor score van 3,6, een promotie en een groot aantal posterpresentaties op internationale congressen. Al met al prachtige resultaten op het gebied van klinisch wetenschappelijk onderzoek in 2012 en 2013, die u nu niet had kunnen lezen als de inzet van Marian Boerstoel, informatiespecialist in het Deventer Ziekenhuis, niet zo tomeloos was geweest. Waarvoor onze grote dank! Wij wensen u veel leesplezier en hopen dat ook 2014 maar een jaar mag worden vol wetenschappelijke inspiratie! Esther van t Riet, wetenschapscoördinator Marjo van den Elsen, verplegingswetenschapper Wetenschapsbureau, Teaching Hospital DZ 2 3

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5 Anesthesiologie Cardiologie Posters Publicaties Single shot femoral nerve block offers superior postoperative mobilisation at an equal analgesia level after total. Knee arthroplasty compared to continuous nerve block using a catheter. Author(s): Heeremans E.H., Pape N., Koorevaar R.C.T., Cobben J.M.G. European Society of Anesthesiology Parijs 9-12 juni 2012 ECG changes after electroconvulsive therapy, cause or consequence? Tuininga YS. Neth Heart J Mar;20(3): Source Department of Cardiology, Deventer Hospital, Nico Bolkesteinlaan 75, 7416 SE, Deventer, the Netherlands. Anesthesiologie Wetenschappelijke Stages Low thoracic versus lumbar epidural anesthesia during the first phase of labor. Auteur: J. Gutteling Begeleider: J.M.G. Cobben Locatie: Anesthesiologie, Deventer Ziekenhuis Periode: oktober 2012 maart 2013 Coronary artery assessment by multidetector computed tomography in patients with prosthetic heart valves. Habets J, van den Brink RB, Uijlings R, Spijkerboer AM, Mali WP, Chamuleau SA, Budde RP. Eur Radiol Jun;22(6): OBJECTIVES: Patients with prosthetic heart valves may require assessment for coronary artery disease. We assessed whether valve artefacts hamper coronary artery assessment by multidetector CT. METHODS: ECG-gated or -triggered CT angiograms were selected from our PACS archive based on the presence of prosthetic heart valves. The best systolic and diastolic axial reconstructions were selected for coronary assessment. Each present coronary segment was scored for the presence of valve-related artefacts prohibiting coronary artery assessment. Scoring was performed in consensus by two observers. RESULTS: Eighty-two CT angiograms were performed on a 64-slice (n = 27) or 256-slice (n = 55) multidetector CT. Eighty-nine valves and five annuloplasty rings were present. Forty-three out of 1160 (3.7%) present coronary artery segments were non-diagnostic due to valve artefacts (14/82 patients). Valve artefacts were located in right coronary artery (15/43; 35%), left anterior descending artery (2/43; 5%), circumflex artery (14/43; 32%) and marginal obtuse (12/43; 28%) segments. All cobalt-chrome containing valves caused artefacts prohibiting coronary assessment. Biological and titanium-containing valves did not cause artefacts except for three specific valve types. CONCLUSIONS: Most commonly implanted prosthetic heart valves do not hamper coronary assessment on multidetector CT. Cobalt-chrome containing prosthetic heart valves preclude complete coronary artery assessment because of severe valve artefacts. KEY POINTS : Most commonly implanted prosthetic heart valves do not hamper coronary artery assessment Prosthetic heart valve composition determines the occurrence of prosthetic heart Cardiologie 6 7

6 Cardiologie valve-related artefacts Björk-Shiley and Sorin tilting disc valves preclude diagnostic coronary artery segment assessment. Warfarin and aspirin in patients with heart failure and sinus rhythm. Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R; WARCEF Investigators. N Engl J Med May 17;366(20): Collaborators (550) Source Columbia University Medical Center, New York, NY 10032, USA. BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT ). Design and methodology of the COACH-2 (Comparative study on guideline adherence and patient compliance in heart failure patients) study: HF clinics versus primary care in stable patients on optimal therapy. Luttik ML, Brons M, Jaarsma T, Hillege HL, Hoes A, de Jong R, Linssen G, Lok DJ, Berger M, van Veldhuisen DJ. Neth Heart J Aug;20(7-8): Source Department of Cardiology, University Medical Center Groningen, University of Groningen, PO BOX , 9700, RB, Groningen, the Netherlands. BACKGROUND: Since the number of heart failure (HF) patients is still growing and long-term treatment of HF patients is necessary, it is important to initiate effective ways for structural involvement of primary care services in HF management programs. However, evidence on whether and when patients can be referred back to be managed in primary care is lacking. AIM: To determine whether long-term patient management in primary care, after initial optimisation of pharmacological and non-pharmacological treatment in a specialised HF clinic, is equally effective as long-term management in a specialised HF clinic in terms of guideline adherence and patient compliance. METHOD: The study is designed as a randomised, controlled, non-inferiority trial. Two-hundred patients will be randomly assigned to be managed and followed in primary care or in a HFclinic. Patients are eligible to participate if they are (1) clinically stable, (2) optimally up-titrated on medication (according to ESC guidelines) and, (3) have received optimal education and counselling on pre-specified issues regarding HF and its treatment. Furthermore, close cooperation between secondary and primary care in terms of back referral to or consultation of the HF clinic will be provided.the primary outcome will be prescriber adherence and patient compliance with medication after 12 months. Secondary outcomes measures will be readmission rate, mortality, quality of life and patient compliance with other lifestyle changes. EXPECTED RESULTS: The results of the study will add to the understanding of the role of primary care and HF clinics in the long-term follow-up of HF patients. Social burden and lifestyle in adults with congenital heart disease. Zomer AC, Vaartjes I, Uiterwaal CS, van der Velde ET, Sieswerda GJ, Wajon Cardiologie 8 9

7 EM, Plomp K, van Bergen PF, Verheugt CL, Krivka E, de Vries CJ, Lok DJ, Grobbee DE, Mulder BJ. Am J Cardiol Jun 1;109(11): Source Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands. We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group. Charcoal or chocolate: what captures the heart? Bijvoet GP, Cramer MJ, Uijlings R, Kirkels JH, Schipper ME. J Clin Pathol Sep;65(9): Iron deficiency in chronic heart failure: an international pooled analysis. Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA. Am Heart J Apr;165(4): Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. BACKGROUND: Iron deficiency (ID) is an emerging problem in patients with chronic heart failure (HF) and can be a potential therapeutic target. However, not much is known about the prevalence, predictors, and prognosis of ID in patients with chronic HF. METHODS: In an international pooled cohort comprising 1,506 patients with chronic HF, we studied the clinical associates of ID and its prognostic consequences. RESULTS: Iron deficiency (defined as a ferritin level <100 μg/l or ferritin μg/l with a transferrin saturation <20%) was present in 753 patients (50%). Anemic patients were more often iron deficient than nonanemic patients (61.2% vs 45.6%, P <.001). Other independent predictors of ID were higher New York Heart Association class, higher N-terminal pro-brain-type natriuretic peptide levels, lower mean corpuscular volume levels, and female sex (all P <.05). During follow-up (median 1.92 years, interquartile range years), 440 patients died (29.2%). Kaplan-Meier survival analysis revealed ID as a strong predictor for mortality (log rank χ(2) 10.2, P =.001). In multivariable hazard models, ID (but not anemia) remained a strong and independent predictor of mortality (hazard ratio 1.42, 95% confidence interval , P =.002). Finally, the presence of ID significantly enhanced risk classification and integrated discrimination improvement when added to a prediction model with established risk factors. CONCLUSIONS: Iron deficiency is common in patients with chronic HF, relates to disease severity, and is a strong and independent predictor of outcome. In this study, ID appears to have greater predictive power than anemia. Cardiologie Cardiac sarcoidosis mimicking non-st-elevation myocardial infarction. Uijlings R, Balt JC, Boom P, Wever E. J Cardiovasc Med (Hagerstown) Apr;13(4): Department of Cardiology, University Medical Center, Utrecht, The Netherlands. Incremental prognostic power of novel biomarkers (growth-differentiation factor-15, high-sensitivity C-reactive protein, galectin-3, and highsensitivity troponin-t) in patients with advanced chronic heart failure. Lok DJ, Klip IT, Lok SI, Bruggink-André de la Porte PW, Badings E, van Wijngaarden J, Voors AA, de Boer RA, van Veldhuisen DJ, van der Meer P. Am J Cardiol Sep 15;112(6): Cardiologie 10 11

8 Cardiologie Source Deventer Hospital, Deventer, the Netherlands. Elevated natriuretic peptides provide strong prognostic information in patients with heart failure (HF). The role of novel biomarkers in HF needs to be established. Our objective was to evaluate the prognostic power of novel biomarkers, incremental to the N-terminal portion of the natriuretic peptide (NT-proBNP) in chronic HF. Concentrations of circulating NT-proBNP, growth differentiation factor 15 (GDF-15), high-sensitivity C-reactive protein (hs-crp), galectin-3 (Gal-3), and high-sensitivity troponin T (hs-tnt) were measured and related to all-cause long-term mortality. Of 209 patients (age 71 ± 10 years, 73% male patients, 97% New York Heart Association class III), 151 (72%) died during a median follow-up of 8.7 ± 1 year. The calculated area under the curve for NT-proBNP was 0.63, GDF , hs-crp 0.66, Gal , and hs-tnt 0.68 (all p <0.01). Each marker was predictive for mortality in univariate analysis. In multivariate analysis, elevated concentrations of GDF-15 (hazard ratio [HR] 1.41, confidence interval [CI] 1.1 to 178, p = 0.005), hs-crp (HR 1.38, CI 1.15 to 1.67, p = 0.001), and hs-tnt (HR 1.27, CI 1.06 to 1.53, p = 0.008) were independently related to mortality. All novel markers had an incremental value to NT-proBNP, using the integrated discrimination improvement. In conclusion, in chronic HF, GDF-15, hs-crp, and hs-tnt are independent prognostic markers, incremental to NT-proBNP, in predicting long-term mortality. In this study, GDF-15 is the most predictive marker, even stronger than NT-proBNP. Optimale hartfalenzorg op lange termijn: vervolgonderzoek van het Deventer-Alkmaar hartfalenproject Pruijsers-Lamers PH Cordiaal 2013;33(5): Stroke in heart failure in sinus rhythm: the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Pullicino PM, Thompson JL, Sacco RL, Sanford AR, Qian M, Teerlink JR, Haddad H, Diek M, Freudenberger RS, Labovitz AJ, Di Tullio MR, Lok DJ, Ponikowski P, Anker SD, Graham S, Mann DL, Mohr JP, Homma S; WAR- CEF Investigators. Cerebrovasc Dis. 2013;36(1):74-8. University of Kent, Canterbury, UK. BACKGROUND: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. METHODS: We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran- Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mrs) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. RESULTS: Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mrs, mrs 90 days after IIS, and change from baseline to post-iis mrs. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mrs 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-iis mrs (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups. CONCLUSIONS: The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin. Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: a subgroup analysis of WARCEF, a randomized controlled trial. Homma S, Thompson JL, Sanford AR, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Massie BM, Labovitz AJ, Di Tullio MR, Gabriel AP, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Circ Heart Fail Sep 1;6(5): Cardiologie 12 13

9 Cardiologie the Division of Cardiology, Department of Medicine. BACKGROUND: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin. METHODS AND RESULTS: We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, ; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, ; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, ; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, ; P=0.03). CONCLUSIONS: In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients 60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included. Effect of a nurse-coordinated prevention programme on cardiovascular risk after an acute coronary syndrome: main results of the RESPONSE randomised trial. Jorstad HT, von Birgelen C, Alings AM, Liem A, van Dantzig JM, Jaarsma W, Lok DJ, Kragten HJ, de Vries K, de Milliano PA, Withagen AJ, Scholte Op Reimer WJ, Tijssen JG, Peters RJ. Heart Oct;99(19): Department of Cardiology, Academic Medical Center-University of Amsterdam, Amsterdam, Noord Holland, The Netherlands. OBJECTIVE: To quantify the impact of a practical, hospital-based nursecoordinated prevention programme on cardiovascular risk, integrated into the routine clinical care of patients discharged after an acute coronary syndrome, as compared with usual care only. DESIGN: RESPONSE (Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) was a randomised clinical trial. SETTING: Multicentre trial in secondary and tertiary healthcare settings. PARTICIPANTS: 754 patients admitted for acute coronary syndrome. INTERVENTION: A nurse-coordinated prevention programme, consisting of four outpatient nurse clinic visits, focusing on healthy lifestyles, biometric risk factors and medication adherence, in addition to usual care. MAIN OUTCOME MEASURES: The main outcome was 10-year cardiovascular mortality risk as estimated by Systematic Coronary Risk Evaluation at 12 months follow-up. Secondary outcomes included Framingham Coronary Risk Score at 12 months, in addition to changes in individual risk factors. Risk factor control was classified as poor if 0 to 3 factors were on target, fair if 4 to 6 factors were on target, and good if 7 to 9 were on target. RESULTS: The mean Systematic Coronary Risk Evaluation at 12 months was 4.4 per cent (SD 4.5) in the intervention group and 5.4 per cent (SD 6.2) in the control group (p=0.021), representing a 17.4% relative risk reduction. At 12 months, risk factor control classified as good was achieved in 35% of patients in the intervention group compared with 25% in the control group (p=0.003). Attendance to the nurse-coordinated prevention programme was 92%. In the intervention group, 86 rehospitalisations were observed against 132 in the control group (relative risk reduction 34.8%, p=0.023). CONCLUSIONS: The nurse-coordinated hospital-based prevention programme in addition to usual care is a practical, yet effective method for reduction of cardiovascular risk in patients with coronary disease. Our data suggest that the counselling component of the programme may lead to a reduction in hospital readmissions. TRIAL REGISTRATION TRIALREGISTERNL IDENTIFIER: TC1290. Early or late intervention in high-risk non-st-elevation acute coronary syndromes: results of the ELISA-3 trial. Badings EA, The SH, Dambrink JH, van Wijngaarden J, Tjeerdsma G, Rasoul S, Timmer JR, van der Wielen ML, Lok DJ, van t Hof AW. EuroIntervention May 20;9(1): Deventer Ziekenhuis, Deventer, The Netherlands. AIMS: To compare an early to a delayed invasive strategy in high-risk patients with NSTE-ACS. METHODS AND RESULTS: In this prospective multicentre trial, 542 patients hospitalised with NSTE-ACS were randomised to either an immediate (an- Cardiologie 14 15

10 Cardiologie giography and revascularisation if appropriate <12 hr) or a delayed invasive strategy (>48 hr after randomisation). Patients were eligible if they had two of the following three high-risk characteristics: evidence of extensive myocardial ischaemia on ECG, elevated biomarkers for myocardial necrosis (TropT >0.10 μg/l), and an age above 65 years. Primary endpoint of the study was the combined incidence of death, reinfarction and/or recurrent ischaemia at 30-day follow-up. Secondary endpoints were enzymatic infarct size as assessed by a single cardiac troponin T, at hours after admission or at discharge, and the percentage of patients without a rise in CKMB during admission. Median age was 71.9 (interquartile range [IQR] ) years. Median time between randomisation and start of angiography was 2.6 (IQR ) hours in the immediate and 54.9 ( ) hours in the delayed intervention group. The composite of death, reinfarction and/or recurrent ischaemia at 30 days occurred in 12% of patients and was not significantly different between the two groups (9.9% and 14.2%, respectively, p=0.135). All secondary endpoints and bleeding complications were comparable. Hospital duration was two days shorter in the immediate intervention group (4 days [IQR 2-10] vs. 6 days [IQR 4-12]). CONCLUSIONS: Although no definitive conclusion can be drawn due to a lower than expected prevalence of the primary endpoint, an immediate invasive strategy was safe and feasible but not superior to a delayed invasive strategy in terms of the combined primary endpoint of death, reinfarction and/or recurrent ischaemia at 30 days. These results are consistent with previous randomised trials which studied the effect of timing of angiography in patients with NSTE-ACS. Trial Registration: ISRCTN Register Galectin-3 is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure. Lok DJ, Lok SI, Bruggink-André de la Porte PW, Badings E, Lipsic E, van Wijngaarden J, de Boer RA, van Veldhuisen DJ, van der Meer P. Clin Res Cardiol Feb;102(2): Deventer Hospital, Nico Bolkesteinlaan 75, 7415 CM, Deventer, The Netherlands. BACKGROUND: Galectin-3 (Gal-3) is a recently discovered marker for myocardial fibrosis and elevated levels are associated with an impaired outcome after short-term follow-up in heart failure (HF) patients. However, whether Gal-3 is related to cardiac remodeling and outcome after long-term follow-up is unknown. Therefore, we determined the utility of Gal-3 as a novel biomarker for left ventricular remodeling and long-term outcome in patients with severe chronic HF. METHODS AND RESULTS: A total of 240 HF patients with New York Heart Association (NYHA) Class III and IV were included. Patients were followed for 8.7 ± 1 years, had a mean age of 71 ± 0.6 years and 73 % of the study population was male. Circulating levels of NT-proBNP and Gal-3 were measured. Serial echocardiography was performed at baseline and at 3 months. At baseline median left ventricular end-diastolic volume (LVEDV) was 267 ml [interquartile range ]. Patients were divided into three groups according to the change in LVEDV. Patients in whom the LVEDV decreased over time had significant lower levels of Gal-3 at entry compared to patients in whom the LVEDV was stable or increased (14.7 vs vs ng/ml; p = for trend), whereas no significant differences were seen in levels of NT-proBNP (p = 0.33). Multivariate linear regression analyses revealed that Gal-3 levels were positively correlated to change in LVEDV (p = 0.007). In addition, Gal-3 was a significant predictor of mortality after long-term followup (p = 0.001). CONCLUSION: Gal-3 is associated with left ventricular remodeling determined by serial echocardiography and predicts long-term mortality in patients with severe chronic HF. Rate control in atrial fibrillation, insight into the RACE II study. Groenveld HF, Crijns HJ, Tijssen JG, Alings M, Hillege HL, Tuininga YS, Van den Berg MP, Van Veldhuisen DJ, Van Gelder IC. Neth Heart J Apr;21(4): Department of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, P.O. Box , 9700 RB, Groningen, the Netherlands. Collaborations 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. N Engl J Med Jul 26;367(4): Collaborators (2737) Van der Sluis A, Lok D 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. Cardiologie 16 17

11 Cardiologie 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 insulinglargine 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, NCT ). 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. N Engl J Med Jul 26;367(4): Collaborators (2737) Van der Sluis A, Lok D 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 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, NCT ). Effects of dalcetrapib in patients with a recent acute coronary syndrome. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Holme IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJ, Mundl H, Nicholls SJ, Shah PK, Tardif JC, Wright RS; dal-outcomes Investigators. N Engl J Med Nov 29;367(22): Collaborators (1041) Lok DJ Cardiology Section, Veterans Affairs Medical Center and University of Colorado School of Medicine, Denver, 80220, USA. gregory.schwartz@va.gov BACKGROUND: In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and Cardiologie 18 19

12 Cardiologie might therefore improve cardiovascular outcomes. METHODS: We randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidencebased care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. RESULTS: At the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons). CONCLUSIONS: In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-outcomes ClinicalTrials.gov number, NCT ). Cardiorenal end points in a trial of aliskiren for type 2 diabetes. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. N Engl J Med Dec 6;367(23): Collaborators (817) Lok D Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. hhparving@dadlnet.dk BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensinconverting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renalreplacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (betweengroup difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with reninangiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT ). Subclinical atrial fibrillation and the risk of stroke. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, Lau CP, Fain E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH; ASSERT Investigators. N Engl J Med Jan 12;366(2): Collaborators (328) Tuininga YS Population Health Research Institute, McMaster University, Hamilton, ON, Canada. BACKGROUND: One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can Cardiologie 20 21

13 detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. METHODS: We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. RESULTS: By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. CONCLUSIONS: Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT ). Voordrachten Resultaten van DEAL-HF studie op lange termijn. Pruijsers-Lamers PH Najaarscongres NVVC Arnhem, 1 november 2013 Early or late intervention in high-risk NSTE-ACS patients: results of the ELISA-3 trial. Badings AE, The SH, Dambrink JH, Van Wijngaarden J, Tjeerdsma G, Rasoul S, Timmer JR, Van der Wielen ML, Lok DJ, Van t Hof AW Euro PCR Parijs, 23 mei 2013 Posters Delayed enhancement versus first-pass perfusion imaging at rest Swart LE, Koster K, Jaspers MMJJR, Van Wijngaarden J, Uijlings R, Badings E, Martens FMAC 99th Scientific Assembly and Annual Meeting of the Radiological Society of North America Chicago USA, 5 dec 2013 Long term results of the DEAL-HF (Deventer-Alkmaar Heart Failure study) after 7-11 year. Pruijsers-Lamers PH, Van Wijngaarden J, Badings E Euro Heart Care 2013 Glasgow, 22 maart 2013 Promotie Novel markers in chronic heart failure / Dirk Jan Arend Lok Rijksuniversiteit Groningen, 22 mei 2013 Cardiologie Cardiologie 22 23

14 Dermatologie Dermatologie Publicaties The first case record of a female patient with buboniclymphogranuloma venereum (LGV), serovariant L2b Stephan P Verweij, Sander Ouburg, Harry de Vries, Servaas A Morre, Cees J W van Ginkel, Hanna Bos, Fré W Sebens Sex Transm Infect 2012;88(5): Since 2003, a lymphogranuloma venereum epidemic has been reported in The Netherlands and other European countries. This epidemic is caused by Chlamydia trachomatis serovariant L2b and has only been seen in men having sex with men. The authors investigated a woman presenting with a bubo in her right groin. The authors showed by real-time PCR that the woman was infected with C trachomatis, serovariant L2b. This is the first reported case study of a female patient with bubonic lymphogranuloma venereum caused by serovariant L2b, which was probably contracted via her bisexual male partner. A case of occupational airborne allergic contact dermatitis caused by faveira amargosa, a tropical timber. Kop EN, van Ginkel CJ, Röckmann H, van der Valk PG. Contact Dermatitis Jun;66(6): Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. [A newborn with an acute itchy skin rash]. [Article in Dutch] Hartmans E, Houwing RH. Ned Tijdschr Geneeskd. 2012;156(48):A4519. Source Deventer Ziekenhuis, afd. Dermatologie, Deventer, the Netherlands. A 36-week-old girl presented with an itching papulous skin eruption symmetrically on her cheeks, buttocks and limbs. Based on the specific clinical presentation she was diagnosed with Gianotti-Crosti-syndrome. This is a self-limiting cutaneous response to a viral infection. [A contractor with damaged knees]. [Article in Dutch] van Laarhoven S, Roerdink WH, van Ginkel CJ. Ned Tijdschr Geneeskd. 2012;156(47):A4561. Source Deventer Ziekenhuis, Deventer, Afd. Heelkunde, the Netherlands. Zie Heelkunde A randomised trial of honey barrier cream versus zinc oxide ointment. Nijhuis WA, Houwing RH, Van der Zwet WC, Jansman FG. Br J Nurs Nov 8-21;21(20):9-10, Ziekenhis Gelderse Vallei Ede, University Groningen, Department of Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands. In this single-blind multicentre, intervention study, 31 patients with symmetrical intertrigo in large skin folds were included to study the clinical effect of two topical treatments, i.e. standard therapy with zinc oxide ointment versus honey barrier cream. Patients were treated twice daily for 21 days, and the severity of intertrigo was scored in an observation period of 21 days. Patients were used as their own controls by treating symmetrical skin folds, on the left and right side. There was no significant difference in treatment effect between intervention groups. For the majority of patients, both treatments were effective. However, the use of honey barrier cream showed lower pruritus complaints (12.9% versus 29.0%). Honey barrier cream is a suitable alternative in the treatment of intertrigo, and promotes patient comfort. Opbrengst van een drempelloze check-je-vlekje dag. Jongeneel E, Van Ginkel CJW Ned T Derm Ven. 2012;22: SCEN-arts en dermatoloog: Een verrijkende combinatie. Houwing RH Ned T Derm Ven. 2013;23(4): Een acneiforme dermatitis door vitamine B12. Van Jarwaarde JA, Houwing RH Ned T Derm Ven. 2013;23(7): Een peuter met één dik oor. Mandigers LCJM, Bom SJH, Dassel ACM, Houwing RH, Van Ginkel CJW Dermatologie 24 25

15 Ned Tijdschr KNO-heelkunde 2013;19:115-6 Zout op je huid, ach wat zou t! Sillevis Smitt JH, Boer J, Van Everdingen JJE Ned T Derm Ven. 2013;23(6):335. Samenvatting Zout is door de eeuwen heen een belangrijke stof geweest. De rol van zout is voor de dermatoloog langzaam maar zeker van minder groot belang geworden. Momenteel lijkt zout met name zinnig in de dermatologie door het bescheiden additieve effect bij de behandeling van atopisch eczeem en psoriasis met UV-therapie. Ook kan intralesionale injectie met een zoutoplossing mogelijk soelaas bieden bij de behandeling van corticosteroïdatrofie. serve as an outcome measure in future studies and a relevant point of intervention for individual patients. Myeloid marker S100A8/A9 and lymphocyte marker, soluble interleukin 2 receptor: biomarkers of hidradenitis suppurativa disease activity? Wieland CW, Vogl T, Ordelman A, Vloedgraven HG, Verwoolde LH, Rensen JM, Roth J, Boer J, Hessels J. Br J Dermatol Jun;168(6): Laboratory for Clinical Chemistry, Deventer Hospital, PO box 5001, 7400 GC Deventer, The Netherlands. : zie Klinische Chemie Dermatologie Depression in patients with hidradenitis suppurativa. Onderdijk AJ, van der Zee HH, Esmann S, Lophaven S, Dufour DN, Jemec GB, Boer J. J Eur Acad Dermatol Venereol Apr;27(4): Source Department of Dermatology, Deventer Hospital, Rotterdam, Netherlands. BACKGROUND: Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory skin disease with abscess formation and scarring predominantly in the inverse areas. The disease is often difficult to treat and patients experience a decreased quality of life (QoL). It is hypothesized that depression is more common in HS patients than among other dermatological patients. OBJECTIVES: To evaluate the prevalence of depression in patients with HS. METHODS: In total 211 HS patients were included in the study and 233 were dermatological control patients. Their QoL and depression scores were assessed using the Dermatology Life Quality Index (DLQI) and the Major Depression Inventory (MDI) questionnaires. HS severity was recorded with a questionnaire and Hurley stages were extracted from the case records. RESULTS: The DLQI was significantly higher for HS patients than for the control patients, 8.4 ± 7.5 vs. 4.3 ± 5.6 (P < ) and correlated with Hurley stage severity scores. Mean MDI scores were significantly higher for HS patients, 11.0 vs. 7.2 (P < ). However, clinically defined depression rates according to the International Classification of Diseases, 10th edition (ICD-10) criteria were not significantly higher in HS patients compared to controls (9% vs. 6%). CONCLUSIONS: HS is a chronic skin disease with major impact on QoL even when compared to other dermatological diseases. MDI scores in HS patients correlate with disease severity. This correlation could indicate that the MDI represents a valid measure of disease related morbidity that may Results of a cosmetovigilance survey in The Netherlands. Salverda JG, Bragt PJ, de Wit-Bos L, Rustemeyer T, Coenraads PJ, Tupker RA, Kunkeler LC, Laheij-de Boer AM, Stenveld HJ, van Ginkel CJ, Kooi MW, Bourgeois FC, van Gorcum TF, van Engelen JG, van Dijk R, de Graaf J, Donker GA, de Heer C, Bruynzeel D. Contact Dermatitis Mar;68(3): Centre for Substances and Integrated Risk Assessment (SIR), National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands. BACKGROUND: Cosmetic products contribute considerably to the incidence of contact dermatitis. In response to a resolution of the Council of Europe, the National Institute for Public Health and the Environment (RIVM) in The Netherlands set up a pilot project to report undesirable effects attributed to cosmetic products. OBJECTIVES: To provide an overview of undesirable effects attributed to cosmetic products and to identify the ingredients involved. The information could contribute to the assessment of whether current EU legislation on cosmetics provides adequate protection. PATIENTS/METHODS: General practitioners, dermatologists and consumers in The Netherlands completed questionnaires on reported undesirable effects of cosmetics. Dermatologists also carried out patch tests and, where necessary, tests with specific batch ingredients of the associated cosmetic product. A website and a public awareness campaign were launched to encourage consumers to report undesirable effects. RESULTS: Between July 2009 and May 2011, the RIVM received more than 1600 reports. Severe undesirable effects were claimed in 1-4% of the cases. The most frequently reported cosmetic products were make-up and moisturi- Dermatologie 26 27

16 Dermatologie sers, and the most frequently identified allergens were isothiazolinones and fragrance ingredients. Three patients tested positive for co-polymers/crosspolymers. CONCLUSIONS: Further investigations are recommended on the prevalence of isothiazolinone-induced allergic contact dermatitis and the allergenic potential of co-polymers/cross-polymers. Voordrachten Therapy for moderate hidradenitis suppurativa with deroofing and topical resorcinol. Boer J Société Bruxelloise de Dermatologie Brussel, België, 7 februari 2013 Boek(bijdrage) Het Geriatrie Formularium 3e ed. Redactie: P.A.F. Jansen, J. van der Laan, J. Schols Hoofdstuk: Decubitus R.H. Houwing Bohn Stafleu Van Loghum, 2012 ISBN: Wetenschappelijke stage A retrospective study on the clinical course of hidradenitis suppurativa. Auteur : I. Deckers Begeleider : J. Boer E.P. Prens Periode : maart augustus 2013 Gynaecologie Publicaties Prediction of recurrence of hypertensive disorders of pregnancy between 34 and 37 weeks of gestation: a retrospective cohort study. van Oostwaard M, Langenveld J, Bijloo R, Wong K, Scholten I, Loix S, Hukkelhoven C, Vergouwe Y, Papatsonis D, Mol B, Ganzevoort W. BJOG Jun;119(7): Source Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, the Netherlands Department of Obstetrics and Gynaecology Deventer Hospital, Deventer, the Netherlands Department of Obstetrics and Gynaecology, Kennemer Gasthuis, Haarlem, the Netherlands Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, the Netherlands The Netherlands Perinatal Registry, Utrecht, the Netherlands Department of Public Health, Erasmus Medical Centre, Rotterdam, the Netherlands Department of Obstetrics and Gynaecology, Amphia Hospital, Breda, the Netherlands. OBJECTIVE: To assess the recurrence risk of late-preterm hypertensive disease of pregnancy, and to determine whether potential risk factors are predictive. Design Retrospective cohort study. Setting Three secondary and three tertiary care hospitals in the Netherlands. Population We identified women with a hypertensive disorder in the index pregnancy and delivery at weeks of gestation, between January 2000 and December METHODS: Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. An adverse outcome was defined as the recurrence of a hypertensive disorder in the next subsequent pregnancy. Main outcome measures Absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive for adverse outcome. RESULTS: We identified 425 women who matched the criteria, of whom 351 could be contacted. Of these women, 189 (54%) had had a subsequent pregnancy. Hypertensive disorders recurred in 96 (51%, 95% CI 43-58%) women, of whom 17 (9%, 95% CI 5-14%) delivered again before 37 weeks of gestation. Chronic hypertension and maternal age were the strongest predictors for recurrence. Women undergoing recurrence had a nine-fold chance of developing chronic hypertension (37% versus 6%, OR 8.7, 95% CI ). Gynaecologie 28 29

17 Gynaecologie CONCLUSIONS: Women with hypertensive disorders and late-preterm delivery have a 50% chance of recurrence, but only a 9% chance of recurrence resulting in delivery before 37 weeks of gestation. Women with chronic hypertension are prone to develop recurrence, and women with a recurrence more often developed chronic hypertension. Size and volume charts of fetal kidney, renal pelvis and adrenal gland. van Vuuren SH, Damen-Elias HA, Stigter RH, van der Doef R, Goldschmeding R, de Jong TP, Westers P, Visser GH, Pistorius LR. Ultrasound Obstet Gynecol Dec;40(6): Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands. OBJECTIVE: To establish reference curves for size and volume of the fetal kidney, renal pelvis and adrenal gland, as measured using ultrasound from the 15(th) week of gestation. METHODS: This was a prospective, longitudinal study of 96 fetuses in low-risk singleton pregnancies, in which we performed serial ultrasound examinations at 4-week intervals. The length and anteroposterior and transverse diameters of both kidneys, the anteroposterior and transverse diameters of the renal pelvises and the length of the adrenal glands were measured three times at each examination, with the average being used for further analysis. Reference charts were constructed using multilevel statistical analysis and comparisons were made with previously published charts derived from cross-sectional data. RESULTS: We present nomograms for fetal kidney dimensions and volume, renal pelvis dimensions and adrenal gland length. The new charts show differences in shape and have narrower percentile bands in comparison to previously published reference ranges. CONCLUSIONS: These new charts of measurements of the fetal kidney, renal pelvis and adrenal gland, from a prospective, longitudinal study, may be useful in the diagnosis and assessment of pathology of the kidney and adrenal gland. Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial. Tajik P, van der Tuuk K, Koopmans CM, Groen H, van Pampus MG, van der Berg PP, van der Post JA, van Loon AJ, de Groot CJ, Kwee A, Huisjes AJ, van Beek E, Papatsonis DN, Bloemenkamp KW, van Unnik GA, Porath M, Rijnders RJ, Stigter RH, de Boer K, Scheepers HC, Zwinderman AH, Bossuyt PM, Mol BW. BJOG Aug;119(9): Academic Medical Centre, Amsterdam, the Netherlands. OBJECTIVE: To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term. DESIGN: A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). SETTING: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. POPULATION: A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between and weeks of gestation randomly allocated to induction of labour or expectant management. METHODS: Data were analysed using logistic regression modelling. MAIN OUTCOME MEASURES: The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes. RESULTS: The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix. CONCLUSION: Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women. TRIAL REGISTRATION: The trial has been registered in the clinical trial register as ISRCTN Integration of patient characteristics and the results of Chlamydia antibody testing and hysterosalpingography in the diagnosis of tubal pathology: an individual patient data meta-analysis. Broeze KA, Opmeer BC, Coppus SF, Van Geloven N, Den Hartog JE, Land JA, Van der Linden PJ, Ng EH, Van der Steeg JW, Steures P, Van der Veen F, Mol BW. Hum Reprod Oct;27(10): Gynaecologie 30 31

18 Gynaecologie Center for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. BACKGROUND: Tubal patency tests are routinely performed in the diagnostic work-up of subfertile patients, but it is unknown whether these diagnostic tests add value beyond the information obtained by medical history taking and findings at physical examination. We used individual patient data metaanalysis to assess this question. METHODS: We approached authors of primary studies for data sets containing information on patient characteristics and results from tubal patency tests, such as Chlamydia antibody test (CAT), hysterosalpingography (HSG) and laparoscopy. We used logistic regression to create models that predict tubal pathology from medical history and physical examination alone, as well as models in which the results of tubal patency tests are integrated in the patient characteristics model. Laparoscopy was considered to be the reference test. RESULTS: We obtained data from four studies reporting on 4883 women. The duration of subfertility, number of previous pregnancies and a history of previous pelvic inflammatory disease (PID), pelvic surgery or Chlamydia infection qualified for the patient characteristics model. This model showed an area under the receiver operating characteristic curve (AUC) of 0.63 [95% confidence interval (CI) ]. For any tubal pathology, the addition of HSG significantly improved the predictive performance to an AUC of 0.74 (95% CI ) (P < 0.001). For bilateral tubal pathology, the addition of both CAT and HSG increased the predictive performance to an AUC of 0.76 (95% CI ). CONCLUSIONS: In the work-up for subfertile couples, the combination of patient characteristics with CAT and HSG results gives the best diagnostic performance for the diagnosis of bilateral tubal pathology. Fatal meningitis during pregnancy in the Netherlands: a nationwide confidential enquiry. Schaap TP, Schutte JM, Zwart JJ, Schuitemaker NW, van Roosmalen J; Dutch Maternal Mortality Committee. BJOG Dec;119(13): Department of Obstetrics and Gynaecology, University Medical Centre Utrecht, the Netherlands. OBJECTIVE: To determine the incidence of maternal deaths attributable to meningitis in the Netherlands, and to assess clinical features and risk factors. DESIGN: Confidential enquiry into the causes of maternal deaths. SETTING: Nationwide in the Netherlands. POPULATION: A total of live births. METHODS: Analysis of all maternal deaths due to meningitis in pregnancy and puerperium from 1983 up to and including 2007 reported to the Maternal Mortality Committee of the Dutch Society of Obstetrics and Gynaecology. MAIN OUTCOME MEASURES: Incidence, clinical features and risk factors. RESULTS: Fifteen maternal deaths occurred due to meningitis, representing 4.4% of all maternal deaths. Twelve women (80%) presented with meningitis during pregnancy, 8 (66%) of them in the third trimester. Presenting symptoms were altered mental status (11; 73%), fever (9; 60%), nuchal rigidity (5; 33%) and headache (13; 87%). Nine women (60%) had otolaryngological infection at presentation or in the previous days or weeks. Twelve women (80%) underwent radiological examination, of which 5 (33%) showed distinct abnormalities. Cerebrospinal fluid (CSF) examination showed infected CSF in 8 (53%) women. In ten women (67%) Streptococcus pneumoniae was isolated. Substandard care was identified in 4 (27%) women. CONCLUSION: Pregnant or puerperal women presenting with classical symptoms of meningitis, particularly those with a history of otolaryngological infection or headache, should undergo thorough investigation and radiological and CSF examinations. Early diagnosis and immediate antibiotic treatment are imperative because of rapid deterioration in pregnant women. In case of doubt, the threshold for antibiotic treatment should be low and close monitoring is warranted. Amniotic fluid embolism incidence, risk factors and outcomes: a review and recommendations. Knight M, Berg C, Brocklehurst P, Kramer M, Lewis G, Oats J, Roberts CL, Spong C, Sullivan E, van Roosmalen J, Zwart J. BMC Pregnancy Childbirth Feb 10;12:7. National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK. BACKGROUND: Amniotic fluid embolism (AFE) is a rare but severe complication of pregnancy. A recent systematic review highlighted apparent differences in the incidence, with studies estimating the incidence of AFE to be more than three times higher in North America than Europe. The aim of this study was to examine population-based regional or national data from five high-resource countries in order to investigate incidence, risk factors and outcomes of AFE and to investigate whether any variation identified could be Gynaecologie 32 33

19 Gynaecologie ascribed to methodological differences between the studies. METHODS: We reviewed available data sources on the incidence of AFE in Australia, Canada, the Netherlands, the United Kingdom and the USA. Where information was available, the risk factors and outcomes of AFE were examined. RESULTS: The reported incidence of AFE ranged from 1.9 cases per maternities (UK) to 6.1 per maternities (Australia). There was a clear distinction between rates estimated using different methodologies. The lowest estimated incidence rates were obtained through validated case identification (range cases per maternities); rates obtained from retrospective analysis of population discharge databases were significantly higher (range per admissions with delivery diagnosis). Older maternal age and induction of labour were consistently associated with AFE. CONCLUSIONS: Recommendation 1: Comparisons of AFE incidence estimates should be restricted to studies using similar methodology. The recommended approaches would be either population-based database studies using additional criteria to exclude false positive cases, or tailored data collection using existing specific population-based systems.recommendation 2: Comparisons of AFE incidence between and within countries would be facilitated by development of an agreed case definition and an agreed set of criteria to minimise inclusion of false positive cases for database studies. Recommendation 3: Groups conducting detailed population-based studies on AFE should develop an agreed strategy to allow combined analysis of data obtained using consistent methodologies in order to identify potentially modifiable risk factors.recommendation 4: Future specific studies on AFE should aim to collect information on management and longer-term outcomes for both mothers and infants in order to guide best practice, counselling and service planning. Severe maternal morbidity and mortality from amniotic fluid embolism in the Netherlands. Stolk KH, Zwart JJ, Schutte J, VAN Roosmalen J. Acta Obstet Gynecol Scand Aug;91(8): Leiden University Medical Centre, Department of Obstetrics, Leiden, the Netherlands. We have assessed the incidence, symptoms and risk factors of amniotic fluid embolism in the Netherlands. Data were retrieved from two nationwide registration systems. From 1983 to 2005 the maternal mortality ratio of amniotic fluid embolism increased from 0.11 to 0.63 (odds ratio (OR) 5.8, 95% confidence interval (CI) ). The most common signs and symptoms of amniotic fluid embolism were dyspnea and massive obstetric hemorrhage. In the majority of women, onset of symptoms was intrapartum or immediately postpartum. Potential risk factors of developing amniotic fluid embolism were maternal age >30, multiparity (OR 3.3, 95% CI ), cesarean section (OR 1.3, 95% CI ) and induction of labor (OR 2.1, 95% CI ). Perinatal mortality was increased to 38.1% compared with 0.98% in the general pregnant population (p < 0.001) High maternal age and multiparity are the most important risk factors for developing amniotic fluid embolism. Severe maternal morbidity in ectopic pregnancy is not associated with maternal factors but may be associated with quality of care. van Mello NM, Zietse CS, Mol F, Zwart JJ, van Roosmalen J, Bloemenkamp KW, Ankum WM, van der Veen F, Mol BW, Hajenius PJ. Fertil Steril Mar;97(3): Department of Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. OBJECTIVE: To study the association between patient-related risk factors and severe maternal morbidity in women with tubal ectopic pregnancy (EP). Furthermore, to identify substandard care factors in clinical care management of EP. DESIGN: Case-control study. SETTING: Not applicable. PATIENT(S): Case subjects were from the LEMMoN study, a prospective nationwide cohort study. Control subjects were from the ESEP study, an international multicenter randomized controlled trial. INTERVENTION(S): Case subjects were women with tubal EP complicated by severe intra-abdominal hemorrhage necessitating blood transfusion of 4 units of packed red blood cells peri- or postoperatively. Control subjects were women with tubal EP who were hemodynamically stable and surgically treated. MAIN OUTCOME MEASURE(S): Patient-related risk factors as: maternal age, gestational age, previous EP, Chlamydia infection, pelvic inflammatory disease, assisted reproductive techniques, and serum hcg level. Substandard care categories classified as unawareness of the clinician, misdiagnosis, and nonadherence to the guideline on EP. RESULT(S): Twenty-nine case subjects and 99 control subjects were included. The mean serum hcg level was significantly higher in case subjects compared with control subjects, but we found no reliable cutoff level of serum hcg to rule out maternal morbidity. Other risk factors did not differ significantly. Substandard care was scored more often in case subjects Gynaecologie 34 35

20 Gynaecologie (43%) than in control subjects (14%), mainly concerning misdiagnosis. CONCLUSION(S): No patient-related risk factors for severe intra-abdominal hemorrhage in women with tubal EP were identified. Our findings underpin the importance of awareness of EP among young fertile women and care providers and clinical care management according to the guidelines to prevent severe maternal morbidity. Tissue composition of the vaginal wall in women with pelvic organ prolapse. Meijerink AM, van Rijssel RH, van der Linden PJ. Gynecol Obstet Invest. 2013;75(1):21-7. Source Department of Gynecology and Obstetrics, Deventer Hospital, Deventer, The Netherlands. BACKGROUND/AIMS: To determine the composition of the vaginal wall and to explore the connective tissue layer, muscularis and basement membrane in relation to the pathogenesis of pelvic organ prolapse (POP). METHODS: We performed a histopathological study with respect to the composition of the vaginal wall of 33 patients and 9 controls. Tissue samples from the vaginal wall were analysed for collagens II and IV, desmin, elastin, fibronectin, smooth muscle actin (SMA) and transforming growth factor (TGF)-β1 using (immuno)histochemistry. Morphometric analyses were also performed. RESULTS: Morphometric characteristics and expression of SMA, TGF-β1, elastin and collagen II were significantly altered in women with POP. CONCLUSION: Our results suggest that there could be an altered tissue composition of the vaginal wall in women with POP. SMA expression could play a role in the pathogenesis of POP. The alterations in elastin and TGF-β1 expression are likely a result of POP. Overweight and severe acute maternal morbidity in a low-risk pregnant population in the Netherlands. Witteveen T, Zwart JJ, Gast KB, Bloemenkamp KW, van Roosmalen J. PLoS One Sep 12;8(9):e Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands. OBJECTIVE: To investigate the association between overweight and severe acute maternal morbidity (SAMM) in a low-risk pregnant population. DESIGN: Nationwide case-control study. SETTING: The Netherlands, august 2004 to august POPULATION: 1567 cases from initially primary care and 2994 women from primary care practices as controls, out of women delivering in the Netherlands during the study period. METHODS: Cases were women with SAMM obtained from a nationwide prospective study. All women in this cohort who initially had low-risk pregnancies were compared with low-risk women without SAMM to calculate odd ratios (ORs) to develop SAMM by body mass index (BMI) category. We divided body mass index in three overweight categories and calculated the ORs (95% CI) of total SAMM and per specific endpoint by logistic regression, with normal weight as reference. We adjusted for age, parity and socio-economic status. MAIN OUTCOME MEASURES: SAMM, defined as Intensive Care Unit (ICU)-admission, Uterine Rupture, Eclampsia or Major Obstetric Haemorrhage (MOH). RESULTS: SAMM was reported in 1567 cases which started as low-risk pregnancies. BMI was available in 1097 (70.0%) cases and 2994 control subjects were included. Analysis showed a dose response relation for overweight (aor, 1.3; 95% CI, ), obese (aor, 1.4; 95% CI, ) and morbidly obese (aor, 2.1; 95% CI, ) women to develop SAMM compared to normal weight. Sub analysis showed the same dose response relation for ICU-admission, Uterine Rupture and Eclampsia. We found no association for MOH. CONCLUSION: Overweight without pre-existent co-morbidity is an important risk-indicator for developing SAMM. This risk increases with an increasing body mass index. The clinical benefit of blood transfusion: a hypothetical experiment based on a nationwide survey of severe maternal morbidity. Hendriks J, Zwart JJ, Briët E, Brand A, van Roosmalen J. Vox Sang Apr;104(3): Department of Obstetrics, Leiden University Medical Centre, Leiden, The Netherlands. BACKGROUND: It is beyond doubt that blood transfusion services have added to the decline in maternal mortality in high-resource countries. To quantify the clinical benefit of red blood cell (RBC) transfusion in obstetric care, we performed a hypothetical experimental study using data from a prospective nationwide cohort of women giving birth in the Netherlands. STUDY DESIGN AND METHODS: Data were abstracted from a nationwide cohort study on severe maternal morbidity, including obstetric haemorrhage Gynaecologie 36 37