2015 Amphia Ziekenhuis

Transcription

1 Amphia Wetenschapsboek 2014

2 Amphia Wetenschapsboek 2014

3 2015 Amphia Ziekenhuis Alle rechten voorbehouden. Niets uit deze uitgave mag worden verveelvoudigd, opgeslagen in een geautomatiseerd gegevensbestand, of openbaar gemaakt, in enige vorm of op enige wijze, hetzij elektronisch, mechanisch, door fotokopieën, opnamen, of enige andere manier, zonder voorafgaande toestemming van de uitgever. Voor zover het maken van kopieën uit deze uitgave is toegestaan op grond van artikel 16B Auteurswet 1912 j het Besluit van 20 juni 1974, St.b. 351, zoals gewijzigd bij Besluit van 23 augustus 1985, St.b. 471 en artikel 17 Auteurswet 1912, dient men de daarvoor wettelijk verschuldigde vergoedingen te voldoen aan de Stichting Reprorecht. Voor het overnemen van gedeelte(n) uit deze uitgave in bloem lezingen, readers en andere compilatie- of andere werken (artikel 16 Auteurswet 1912), in welke vorm dan ook, dient men zich tot de samenstellers/vormgever te wenden. De inzichten in de geneeskunde en wetenschap zijn voortdurend aan verandering onderhevig als gevolg van onderzoek en ervaring. De auteurs en uitgever zijn uiterst zorgvuldig te werk gegaan, om ervoor te zorgen dat de in dit boek verstrekte informatie, in overeenstemming is met de huidige kennis van zaken. Dit ontslaat de gebruiker van het boek echter niet van de verplichting om aan de hand van bestaande richtlijnen, protocollen en wetenschappelijke informatie te controleren of de daar verstrekte informatie afwijkt van de gegevens in dit boek en daarmee vast te stellen of de inhoud nog in overeenstemming is met de huidige stand van zaken ten aanzien van kennis en handelen. Ondanks alle aan de samenstelling van deze uitgave bestede zorg, zullen noch de samenstellers, noch de vormgever aansprakelijkheid aanvaarden voor eventuele schade die zou kunnen voortvloeien uit enige fout die in deze uitgave zou kunnen voorkomen. 2

4 Voorwoord Sinds vele jaren publiceert het Amphia Ziekenhuis een overzicht van alle wetenschappelijke publicaties van het afgelopen jaar. Zo ook dit jaar. Eerder was er alleen aandacht voor publicaties in het medisch domein, maar de recente ontwikkelingen maken duidelijk dat de wetenschappelijke ontwikkeling van de ziekenhuiszorg meer omvat dan de geneeskunde. Om die reden is in het nu voorliggende wetenschapsboek een brede variatie van onderzoeksresultaten te vinden. Verheugend is dat velen inmiddels de weg naar een promotietraject hebben gevonden. Amphia stimuleert dit nadrukkelijk. Dit past bij het zijn van een Top Klinisch Opleidingsziekenhuis en houdt de hele Amphiagemeenschap bij de les en gericht op het verrijken van kennis. Los van de wetenschappelijke productie in de vorm van publicaties, zoals in deze bundel weergegeven, werd in 2014 ook de eerste klinische Amphia-leerstoel gevestigd. Collega Joachim Aerts, longarts, werd benoemd tot hoogleraar Longoncologie (in het bijzonder mesothelioom) aan de Erasmus Universiteit te Rotterdam. Professor Aerts is een nationaal en internationaal erkend deskundige op dit bijzondere deel van de longgeneeskunde. Op 24 april 2015 heeft hij zijn oratie gehouden. Namens het Directiecomité wens ik u veel leesplezier bij dit zevende wetenschapsboek. Dr. J.J. (Hans) Meij MBA, lid Directiecomité 3

5 Inhoud Publicaties Medische Staf 6 Anesthesiologie 6 Cardiologie 14 Cardiothoracale Chirurgie 43 Chirurgie 46 Dermatologie 64 Gynaecologie / Verloskunde 65 Interne Geneeskunde en Maag-, Darm-, Levergeneeskunde 81 Keel-, Neus- en Oorheelkunde 102 Kindergeneeskunde 104 Klinisch Chemisch Hematologisch Laboratorium 108 Klinische Farmacie 112 Klinische Geriatrie 115 Laboratorium voor Microbiologie en Infectiepreventie 116 Longgeneeskunde 134 Mondziekten, Kaak- en Aangezichtschirurgie 144 Neurologie / Neurochirurgie 148 Oogheelkunde 150 Orthopedie 152 Pathologisch Anatomisch Laboratorium 168 Radiologie 169 Urologie 174 4

6 Publicaties arts-assistenten 176 Anesthesiologie 176 Chirurgie 176 Interne Geneeskunde en Maag-, Darm-, Levergeneeskunde 186 Klinisch Chemisch Hematologisch Laboratorium 187 Laboratorium voor Microbiologie en Infectiepreventie 188 Longgeneeskunde 194 Orthopedie 196 Publicaties medewerkers zorg- en kenniskernen en Directiecomité 198 Klinisch Chemisch Hematologisch Laboratorium 198 Laboratorium voor Microbiologie en Infectiepreventie 199 Amphia Academy Infectious Disease Foundation 208 Orthopedie 212 Directiecomité 213 Register Medische Staf 214 Register arts-assistenten 247 Register medewerkers zorg- en kenniskernen en Directiecomité 251 5

7 Publicaties Medische Staf Anesthesiologie Kerngegevens 29 anesthesiologen: A. (Anna) Besselink-Lobanova, S.F. (Sjoerd) de Boer, H.P. (Henk) van Driel, M.J.P.G. (Maarten) van Eerd, F.E.A. (Ferd) Geisler, G. (Gerhard) van Gelder, dr. B.M. (Bas) Gerritse, C. (Carla) van Gompel, P. (Pim) van der Heiden, dr. V.L.H. (Vincent) Hoffmann, L.H. (Lode) Jacobs, G.M.J. (Greg) Jansen, A. (Aad) van Keeken, J.D.L. (Johan) Konings, F. (Frank) de Loos, P.P.M. (Paul) Maas, dr. B.J.M. (Nardo) van der Meer, R.J. (Robert) Meulemans, F.X. (Frank) O Connor, P.M.J. (Peter) Rosseel, T.A. (Tom) Rijpstra, D.B. (David) Schockman, T.V. (Thierry) Scohy, G.C.H. (Gilbert) Tjiang, M.W.A. (Miriam) van der Velden, W.A. (Anton) Visser, M.A.J. (Michael) Voets, E. (Erik) Winters, S.I.M. (Simone) van Zijll Langhout-Kokke 1 SPIDMA: I. (Iris) Witsch Chef de clinique: S. (Sylvia) Kilwinger, S. (Stefan) Boeckx, H. (Hester) Boesjes Internist-intensivist: R.A.L. (Ruud) de Waal, F.J. (Frits) Schuitemaker Longarts-intensivist: K.M. (Merijn) Kant 1 CDC pijnanesthesioloog: P.A.V. (Peter) Frietman 8 arts-assistenten niet in opleiding op de ICU (5,5 fte) 6

8 Samenvattingen gepubliceerde artikelen Tolsma M, Bentala M, Rosseel P, Gerritse BM, Dijkstra H, Mulder P, van der Meer N. The value of routine chest radiographs after minimally invasive cardiac surgery: an observational cohort study. J Cardiothorac Surg Nov 11;9(1):174. [Epub ahead of print]. BACKGROUND: Chest radiographs (CXRs) are obtained frequently in postoperative cardiac surgery patients. The diagnostic and therapeutic efficacy of routine CXRs is known to be low and the discussion regarding the safety of abandoning these CXRs after cardiac surgery is still ongoing. We investigated the value of routine CXRs directly after minimally invasive cardiac surgery. METHODS: We prospectively included all patients who underwent minimally invasive cardiac surgery by port access, ministernotomy or bilateral video-assisted thoracoscopy (VATS) in the year A direct postoperative CXR was performed on all patients at ICU arrival. All CXR findings were noted, including whether they led to an intervention or not. RESULTS: The results were compared to the postoperative CXR results in patients who underwent conventional cardiac surgery by full median sternotomy over the same period.main resultsa total of 249 consecutive patients were included. Most of these patients underwent valve surgery, rhythm surgery or a combination of both. The diagnostic efficacy for minor findings was highest in the port access and bilateral VATS groups (56% and 63% versus 28% and 45%) (p < 0.005). The diagnostic efficacy for major findings was also higher in these groups (8.9% and 11% versus 4.3% and 3.8%) (p = 0.010). The need for an intervention was most common after minimally invasive surgery by port access, although this difference was not statistically significant (p = 0.056). CONCLUSION: The diagnostic efficacy of routine CXRs performed after minimally invasive cardiac surgery by port access or bilateral VATS is higher than the efficacy of CXRs performed after conventional cardiac surgery. A routine CXR after these procedures should still be considered. PMID: PMCID: PMC Derikx HJ, Gerritse BM, Gans R, van der Meer NJ. A randomized trial comparing two intraosseous access devices in intrahospital healthcare providers with a focus on retention of knowledge, skill, and self-efficacy. Eur J Trauma Emerg Surg. 2014;40: INTRODUCTION: Intraosseous access is recommended in vitally compromised patients if an intravenous access cannot be easily obtained. Intraosseous infusion can be initiated by various healthcare providers. Currently, there are two mechanical intraosseous devices approved by the U.S. Food and Drug Administration (FDA) for use in adults and children. A comparison is made in this study of the theoretical and practical performance by anesthesiologists and registered nurses of anesthesia (RNAs) in the use of the battery-powered device (device A) versus the Anesthesiologie 7

9 spring-loaded needle device (device B). This study entailed a 12-month follow-up of knowledge, skill retention, and self-efficacy measured by standardized testing. METHODS: A prospective randomized trial was performed, initially comparing 15 anesthesiologists and 15 RNAs, both on using the two types of intraosseous devices. A structured lecture and skill station was given with the educational aids provided by the respective manufacturers. Individual knowledge and practical skills were tested at 0, 3, and 12 months after the initial course. RESULTS: There was no statistical significant difference in the retention of theoretical knowledge between RNAs and anesthesiologists on all testing occasions. However, the self-efficacy of the anesthesiologists is significantly higher (p < 0.01) than the self-efficacy of the RNAs for both devices, on any testing occasion. Insufficient skills were local disinfection (both groups, both devices) and attachment of the needle to the intravenous line (RNAs with both devices). In 33% of all device B handlings, unsafe practice occurred. CONCLUSION: The use of device A is safer in handling in comparison to device B at 12 months follow-up. The hypothesis that doctors are more qualified in obtaining intraosseous access has been disproven, as anesthesiologists were as successful as RNAs. However, the low self-efficacy of RNAs in the use of intraosseous devices could diminish the chance of them actually using one. Hogervorst E, Rosseel P, van der Bom J, Bentala M, Brand A, van der Meer N, van de Watering L. Tolerance of intraoperative hemoglobin decrease during cardiac surgery. Transfusion Oct;54(10 Pt 2): Epub 2014 Apr 14. BACKGROUND: It has been suggested that a decrease of at least 50% from the preoperative hemoglobin (Hb) level during cardiac surgery is associated with adverse outcomes even if the absolute Hb level remains above the commonly used transfusion threshold of 7.0 g/dl. In this study the relation between intraoperative Hb decline of at least 50% and a composite endpoint was analyzed. STUDY DESIGN AND METHODS: This single-center study comprised 11,508 patients who underwent cardiac surgery and had normal preoperative Hb levels ( g/dl in women, g/dl in men) between January 2001 and December Logistic regression modeling was used. The composite endpoint comprised in-hospital mortality, stroke, myocardial infarction, and renal failure. 8 Publicaties Medische Staf

10 RESULTS: Patients whose Hb did not decrease at least 50% and remained above 7 g/dl were used as reference (n = 9672). A total of 363 (3.2%) patients had an intraoperative Hb of less than 7 g/dl during surgery but a Hb decrease of less than 50%; 876 patients (7.4%) showed both a nadir Hb less than 7 g/dl and a Hb decrease of at least 50%, while 597 (5.2%) had a Hb decrease of at least 50% and a nadir Hb of at least 7 g/dl. In this last group the incidence of the composite endpoint was higher than in patients in the reference group (adjusted odds ratio, 1.27; 95% confidence interval, ).CONCLUSIONS: Our findings show that a decrease of at least 50% from baseline Hb during cardiac surgery is associated with adverse outcomes, even if the absolute Hb level remains higher than the commonly used transfusion threshold of 7.0 g/dl. PMID: Joosen AM, Boonen K, Hulsman N, Schuitemaker FJ, Thelen MH. Hypernatraemia in disguise. Clin Chem Lab Med Nov;52(11):e No abstract available. PMID: Bunge JJ, van Osch D, Dieleman JM, Jacob KA, Kluin J, van Dijk D, Nathoe HM; Dexamethasone for Cardiac Surgery (DECS) Study Group* [Van der Meer NJ, Rosseel PM et al...]. Dexamethasone for the prevention of postpericardiotomy syndrome: A DExamethasone for Cardiac Surgery substudy. Am Heart J Jul;168(1): e1. Epub 2014 Apr 5. BACKGROUND: The postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery. The pathophysiology remains unclear, although evidence exists that surgical trauma and the use of cardiopulmonary bypass provoke an immune response leading to PPS. We hypothesized that an intraoperative dose of dexamethasone decreases the risk of PPS, by reducing this inflammatory response. METHODS: We performed a subanalysis of the DECS study, which is a multicenter, double-blind, placebo-controlled, randomized trial of 4,494 patients undergoing cardiac surgery with use of cardiopulmonary bypass. The aim of the DECS study was to investigate whether a single intraoperative dose of 1 mg/kg dexamethasone reduced the incidence of a composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. In this substudy, we retrospectively analyzed the occurrence of PPS in 822 patients who were included in the DECS trial and underwent valvular surgery. Postpericardiotomy syndrome was diagnosed if 2 of 5 listed symptoms were present: unexplained fever, pleuritic chest pain, pericardial or pleural rub, new or worsening pericardial or pleural effusion. All medical charts, x-rays, and echocardiograms were reviewed. Secondary end point was the occurrence of complicated PPS, defined as PPS with need for evacuation of pleural effusion, pericardiocentesis, and tamponade requiring intervention or hospital readmission for PPS. This is a blinded, singlecenter, post hoc analysis. Anesthesiologie 9

11 RESULTS: Postpericardiotomy syndrome occurred in 119 patients (14.5%). The incidence of PPS after dexamethasone compared with placebo was 13.5% vs 15.5% (relative risk 0.88, 95% CI ). For complicated PPS, the incidence was 3.8% versus 3.2% (relative risk 1.17, 95% CI , P =.66), respectively. CONCLUSION: In patients undergoing valvular cardiac surgery, high-dose dexamethasone treatment had no protective effect on the occurrence of PPS or complicated PPS. Collaborators: Bredée JJ, Buhre WF, Dieleman JM, van Dijk D, van Herwerden LA, Kalkman CJ, van Klarenbosch J, Moons KG, Nathoe HM, Numan SC, Ottens TH, Roes KC, Sauer AM, Slooter AJ, Nierich AP, Ennema JJ, Rosseel PM, van der Meer NJ, van der Maaten JM, Cernak V, Hofland J, van Thiel RJ, Diephuis JC, Schepp RM, Haenen J, de Lange F, Boer C, de Jong JR, Tijssen JG. PMID: Van Eerd M, Patijn J, Sieben JM, Sommer M, Van Zundert J, van Kleef M, Lataster A. Ultrasonography of the cervical spine: an in vitro anatomical validation model. Anesthesiology Jan;120(1): BACKGROUND: Anatomical validation studies of cervical ultrasound images are sparse. Validation is crucial to ensure accurate interpretation of cervical ultrasound images and to develop standardized reliable ultrasound procedures to identify cervical anatomical structures. The aim of this study was to acquire validated ultrasound images of cervical bony structures and to develop a reliable method to detect and count the cervical segmental levels. METHODS: An anatomical model of a cervical spine, embedded in gelatin, was inserted in a specially developed measurement device. This provided ultrasound images of cervical bony structures. Anatomical validation was achieved by laser light beams projecting the center of the ultrasound image on the cervical bony structures through a transparent gelatin. RESULTS: Anatomically validated ultrasound images of different cervical bony structures were taken from dorsal, ventral, and lateral perspectives. Potentially relevant anatomical landmarks were defined and validated. Test/retest analysis for positioning showed a reproducibility with an intraclass correlation coefficient for single measures of Besides providing validated ultrasound images of bony structures, this model helped to develop a method to detect and count the cervical segmental levels in vivo at long-axis position, in a dorsolateral (paramedian) view at the level of the laminae, starting from the base of the skull and sliding the ultrasound probe caudally. 10 Publicaties Medische Staf

12 CONCLUSIONS: Ultrasound bony images of the cervical vertebrae were validated with an in vitro model. Anatomical bony landmarks are the mastoid process, the transverse process of C1, the tubercles of C6 and C7, and the cervical laminae. Especially, the cervical dorsal laminae serve best as anatomical bony landmarks to reliably detect the cervical segmental levels in vivo. Comment in: On the fabric of the human body and modern ultrasound imaging. [Anesthesiology. 2014] PMID: Spoelstra-de Man AM, van der Heiden P, Spijkstra JJ, Verheijen AT, Kooter AJ. Treatment of hyperglycaemia in diabetic ketoacidosis: natura non facit saltus. Neth J Med Jan;72(1):54-8. In the treatment of severe diabetic ketoacidosis the gradual correction of glucose, electrolyte and fluid derangements is of utmost importance. In this paper the authors provide practical recommendations for these corrections based on novel pathophysiological insights. PMID: Hulsman N, Hiddema PA, Veen EJ, van der Meer NJ. Traumatic cardiac injury by gun nails. Int J Crit Illn Inj Sci Apr;4(2): No abstract available. Ottens TH, Dieleman JM, Sauër AM, Peelen LM, Nierich AP, de Groot WJ, Nathoe HM, Buijsrogge MP, Kalkman CJ, van Dijk D; Dexamethasone for Cardiac Surgery (DECS) Study Group [Van der Meer NJ et al...]. Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial. Anesthesiology Sep;121(3): BACKGROUND: Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characterized by impaired memory function and intellectual ability. The systemic inflammatory response that is induced by major surgery and cardiopulmonary bypass may play an important role in the etiology of POCD. Prophylactic corticosteroids to attenuate the inflammatory response may therefore reduce the risk of POCD. The authors investigated the effect of intraoperative high-dose dexamethasone on the incidence of POCD at 1 month and 12 months after cardiac surgery. Anesthesiologie 11

13 METHODS: This multicenter, randomized, double-blind, placebo-controlled trial is a preplanned substudy of the DExamethasone for Cardiac Surgery trial. A total of 291 adult patients undergoing cardiac surgery with cardiopulmonary bypass were recruited in three hospitals and randomized to receive dexamethasone 1 mg/kg (n = 145) or placebo (n = 146). The main outcome measures were incidence of POCD at 1- and 12-month follow-up, defined as a decline in neuropsychological test performance beyond natural variability, as measured in a control group. RESULTS: At 1-month follow-up, 19 of 140 patients in the dexamethasone group (13.6%) and 10 of 138 patients in the placebo group (7.2%) fulfilled the diagnostic criteria for POCD (relative risk, 1.87; 95% CI, 0.90 to 3.88; P = 0.09). At 12-month follow-up, 8 of 115 patients in the dexamethasone group (7.0%) and 4 of 114 patients (3.5%) in the placebo group had POCD (relative risk, 1.98; 95% CI, 0.61 to 6.40; P = 0.24). CONCLUSION: Intraoperative high-dose dexamethasone did not reduce the risk of POCD after cardiac surgery. PMID: Tolsma M, Rijpstra TA, Schultz MJ, Mulder PG, van der Meer NJ. Significant changes in the practice of chest radiography in Dutch intensive care units: a web-based survey. Ann Intensive Care Apr 4;4(1):10. BACKGROUND: ICU patients frequently undergo chest radiographs (CXRs). The diagnostic and therapeutic efficacy of routine CXRs are now known to be low, but the discussion regarding specific indications for CXRs in critically ill patients and the safety of abandoning routine CXRs is still ongoing. We performed a survey of Dutch intensivists on the current practice of chest radiography in their departments. METHODS: Web-based questionnaires, containing questions regarding ICU characteristics, ICU patients, daily CXR strategies, indications for routine CXRs and the practice of radiologic evaluation, were sent to the medical directors of all adult ICUs in the Netherlands. CXR strategies were compared between all academic and non-academic hospitals and between ICUs of different sizes. A comparison was made between the survey results obtained in 2006 and RESULTS: Of the 83 ICUs that were contacted, 69 (83%) responded to the survey. Only 7% of responding ICUs were currently performing daily routine CXRs for all patients, and 61% of the responding ICUs were said never to perform CXRs on a routine basis. A daily meeting with a radiologist is an established practice in 72% of the responding ICUs and is judged to be important or even essential by those ICUs. 12 Publicaties Medische Staf

14 The therapeutic efficacy of routine CXRs was assumed by intensivists to be lower than 10% or to be between 10 and 20%. The efficacy of on-demand CXRs was assumed to be between 10 and 60%. There is a consensus between intensivists to perform a routine CXR after endotracheal intubation, chest tube placement or central venous catheterization. CONCLUSION: The strategy of daily routine CXRs for critically ill and mechanically ventilated patients has turned from being a common practice in 2006 to a rare current practice. Other routine strategies and an on-demand only strategy have become more popular. Intensivists still assume the value of CXRs to be higher than the efficacy that is reported in the literature. PMID: PMCID: PMC Dietrich W, Faraoni D, von Heymann C, Bolliger D, Ranucci M, Sander M, Rosseel P. ESA guidelines on the management of severe perioperative bleeding: comments on behalf of the Subcommittee on Transfusion and Haemostasis of the European Association of Cardiothoracic Anaesthesiologists. Eur J Anaesthesiol Apr;31(4): Comment in: Reply to: ESA guidelines on the management of severe perioperative bleeding. [Eur J Anaesthesiol. 2014] Comment on: Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. [Eur J Anaesthesiol. 2013] PMID: Anesthesiologie 13

15 Cardiologie Kerngegevens 15 cardiologen: dr. A.M.W. (Marco) Alings, dr. B.J.L. (Ben) van den Branden, W.A.J. (Wim) Bruggeling, dr. P.H.J.M. (Peter) Dunselman, H.P.J. (Henry) de Haan, dr. P. (Peter) den Heijer, dr. B. (Bart) Hooft van Huysduynen, dr. M. (Martijn) Meuwissen, S.G (Sander) Molhoek, dr. J. (Jeroen) Schaap, dr. B. (Bas) Schölzel, dr. S. (Sipke) Strikwerda, dr. J. (Jeroen) Vos, dr. R.P. (Rob) Wielenga, dr. W.J.M. Dewilde Chef de clinique: dr. D.P.W. (Driek) Beelen 3 assistenten in opleiding (gemiddeld 1,16 fte) 10 assistenten niet in opleiding (11 fte) 4 verpleegkundig specialisten (3,35 fte) Subspecialismen: algemene cardiologie (hart- en vaatziekten in brede zin), beeldvorming (echocardiografie, cardiale CT en MRI), interventiecardiologie (stent- en dotterbehandelingen, vervanging hartklep), elektrofysiologie (behandeling van hartritmestoornissen) 14 Publicaties Medische Staf

16 Samenvattingen gepubliceerde artikelen Held C, Hylek EM, Alexander JH, Hanna M, Lopes RD, Wojdyla DM, Thomas L, Al-Khalidi H, Alings M, Xavier D, Ansell J, Goto S, Ruzyllo W, Rosenqvist M, Verheugt FW, Zhu J, Granger CB, Wallentin L. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J Dec 12. [Epub ahead of print]. AIM: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. METHODS AND RESULTS: Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of 2 g/dl or transfusion of 2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ich, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ich bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR (95% CI ) as was stroke or MI with HR (95% CI ), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. CONCLUSION: Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. CLINICAL TRIALSGOV IDENTIFIER: NCT PMID: Cardiologie 15

17 Habibovi M, Denollet J, Cuijpers P, Spek VR, van den Broek KC, Warmerdam L, van der Voort PH, Herrman JP, Bouwels L, Valk SS, Alings M, Theuns DA, Pedersen SS. E-health to manage distress in patients with an implantable cardioverter-defibrillator: primary results of the WEBCARE trial. Psychosom Med Oct;76(8): The Web-based distress management program for patients with an implantable cardioverterdefibrillator (ICD; WEBCARE) was developed to mitigate distress and enhance health-related quality of life in ICD patients. This study investigated the treatment effectiveness at 3-month follow-up for generic and disease-specific outcome measures. METHODS: Consecutive patients implanted with a first-time ICD from six hospitals in the Netherlands were randomized to either the WEBCARE or the usual care group. Patients in the WEBCARE group received a 12-week fixed, six-lesson behavioral treatment based on the problemsolving principles of cognitive behavioral therapy. RESULTS: Two hundred eighty-nine patients (85% response rate) were randomized. The prevalence of anxiety and depression ranged between 11% and 30% and 13% and 21%, respectively. No significant intervention effects were observed for anxiety (ß = 0.35; p =.32), depression (ß = -0.01; p =.98) or health-related quality of life (Mental Component Scale: ß = 0.19; p =.86; Physical Component Scale: ß = 0.58; p =.60) at 3 months, with effect sizes (Cohen d) being small (range, ). There were also no significant group differences as measured with the disease-specific measures device acceptance (ß = -0.37; p =.82), shock anxiety (ß = 0.21; p =.70), and ICD-related concerns (ß = -0.08; p =.90). No differences between treatment completers and noncompleters were observed on any of the measures. CONCLUSIONS: In this Web-based intervention trial, no significant intervention effects on anxiety, depression, health-related quality of life, device acceptance, shock anxiety, or ICD-related concerns were observed. A more patient tailored approach targeting the needs of different subsets of ICD patients may be warranted. TRIAL REGISTRATION: clinicaltrials.gov. Identifier: NCT Comment in: Distance therapy to improve symptoms and quality of life: complementing office-based care with telehealth. [Psychosom Med. 2014] PMID: Vanassche T, Lauw MN, Eikelboom JW, Healey JS, Hart RG, Alings M, Avezum A, Díaz R, Hohnloser SH, Lewis BS, Shestakovska O, Wang J, Connolly SJ. Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur Heart J Feb 1;36(5): Epub 2014 Sep Publicaties Medische Staf

18 AIMS: The pattern of atrial fibrillation (AF) occurrence-paroxysmal, persistent, or permanentis associated with progressive stages of atrial dysfunction and structural changes and may therefore be associated with progressively higher stroke risk. However, previous studies have not consistently shown AF pattern to predict stroke but have been hampered by methodological shortcomings of low power, variable event ascertainment, and variable anticoagulant use. METHODS AND RESULTS: We analysed the rates of stroke and systemic embolism in 6563 aspirin-treated patients with AF from the ACTIVE-A/AVERROES databases. There was thorough searching for events and adjudication. Multivariable analyses were performed with the adjustment for known risk factors for stroke. Mean age of patients with paroxysmal, persistent, and permanent AF was 69.0 ± 9.9, 68.6 ± 10.2, and 71.9 ± 9.8 years (P < 0.001). The CHA2DS2-VASc score was similar in patients with paroxysmal and persistent AF (3.1 ± 1.4), but was higher in patients with permanent AF (3.6 ± 1.5, P < 0.001). Yearly ischaemic stroke rates were 2.1, 3.0, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjusted hazard ratio of 1.83 (P < 0.001) for permanent vs. paroxysmal and 1.44 (P = 0.02) for persistent vs. paroxysmal. Multivariable analysis identified age 75 year, sex, history of stroke or TIA, and AF pattern as independent predictors of stroke, with AF pattern being the second strongest predictor after prior stroke or TIA. CONCLUSION: In a large population of non-anticoagulated AF patients, pattern of AF was a strong independent predictor of stroke risk and may be helpful to assess the risk/benefit for anticoagulant therapy, especially in lower risk patients. Published on behalf of the European Society of Cardiology. All rights reserved. The Author For permissions please journals.permissions@oup.com. PMID: Mulder BA, Van Veldhuisen DJ, Crijns HJ, Tijssen JG, Hillege HL, Alings M, Rienstra M, Van den Berg MP, Van Gelder IC; RACE II Investigators. Digoxin in patients with permanent atrial fibrillation: data from the RACE II study. Heart Rhythm Sep;11(9): Epub 2014 Jun 9. BACKGROUND: The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation. OBJECTIVES: To assess the association of digoxin with cardiovascular (CV) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets. METHODS: The primary outcome was a composite of CV morbidity and mortality. Secondary outcomes included CV hospitalization and all-cause mortality or heart failure (HF) hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment phase. Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up. The median follow-up period was 2.9 years (interquartile range years). Cardiologie 17

19 RESULTS: In total, 284 patients (46.7%) used digoxin after the dose-adjustment phase (median dosage mg; interquartile range mg). These patients were more often women, previously admitted for HF, had an increased left ventricular end-systolic diameter, and more often randomized to strict rate control. By using Cox proportional hazards regression analysis, the use of digoxin was not associated with an increased risk for the primary and secondary outcomes. For the primary outcome, the 3-year estimated cumulative incidence was 12.9% vs 13.4% in the digoxin group vs the no-digoxin group (unadjusted hazard ratio [HR] 0.97; 95% confidence interval [CI] ). Incidence was 19.4% vs. 19.5% for CV hospitalization (unadjusted HR 1.00; 95% CI ) and 6.6% vs. 9.9% for all-cause mortality or HF hospitalization (unadjusted HR 0.62; 95% CI ) in the digoxin group vs the no-digoxin group. CONCLUSION: The use of digoxin was not associated with increased morbidity and mortality. PMID: Blankestijn PJ, Alings M, Voskuil M, Grobbee DE. The complexity after simplicity: How to proceed with renal denervation in hypertension? Eur J Prev Cardiol Jun 9. pii: [Epub ahead of print] PubMed PMID: No abstract available. PMID: Habibovi M, Cuijpers P, Alings M, van der Voort P, Theuns D, Bouwels L, Herrman JP, Valk S, Pedersen S. Attrition and adherence in a WEB-Based Distress Management Program for Implantable Cardioverter defibrillator Patients (WEBCARE): randomized controlled trial. J Med Internet Res Feb 28;16(2):e52. BACKGROUND: WEB-Based Distress Management Program for Implantable CARdioverter defibrillator Patients (WEBCARE) is a Web-based randomized controlled trial, designed to improve psychological well-being in patients with an implantable cardioverter defibrillator (ICD). As in other Web-based trials, we encountered problems with attrition and adherence. OBJECTIVE: In the current study, we focus on the patient characteristics, reasons, and motivation of (1) completers, (2) those who quit the intervention, and (3) those who quit the intervention and the study in the treatment arm of WEBCARE. METHODS: Consecutive first-time ICD patients from six Dutch referral hospitals were approached for participation. After signing consent and filling in baseline measures, patients were randomized to either the WEBCARE group or the Usual Care group. 18 Publicaties Medische Staf

20 RESULTS: The treatment arm of WEBCARE contained 146 patients. Of these 146, 34 (23.3%) completed the treatment, 88 (60.3%) dropped out of treatment but completed follow-up, and 24 (16.4%) dropped out of treatment and study. Results show no systematic differences in baseline demographic, clinical, or psychological characteristics between groups. A gradual increase in dropout was observed with 83.5% (122/146) completing the first lesson, while only 23.3% (34/146) eventually completed the whole treatment. Reasons most often given by patients for dropout were technical problems with the computer, time constraints, feeling fine, and not needing additional support. CONCLUSIONS: Current findings underline the importance of focusing on adherence and dropout, as this remains a significant problem in behavioral Web-based trials. Examining possibilities to address barriers indicated by patients might enhance treatment engagement and improve patient outcomes. TRIAL REGISTRATION: Clinicaltrials.gov: NCT ; NCT (Archived by WebCite at PMID: PMCID: PMC Wallentin L, Lopes RD, Hanna M, Thomas L, Hellkamp A, Nepal S, Hylek EM, Al-Khatib SM, Alexander JH, Alings M, Amerena J, Ansell J, Aylward P, Bartunek J, Commerford P, De Caterina R, Erol C, Harjola VP, Held C, Horowitz J, Huber K, Husted S, Keltai M, Lanas F, Lisheng L, McMurray JJ, Oh BH, Rosenqvist M, Ruzyllo W, Steg PG, Vinereanu D, Xavier D, Granger CB. Response to letter regarding article, Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation Jan 14;129(2):e21-2. Letter by Replogle and Moore regarding article, Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. [Circulation. 2013]. Dello SA, Alings M. Reply to letter from J. Finsterer and S. Zarrouk-Mahjoub. Neth Heart J Jun;22(6):306. No abstract available. PMID: PMC Cardiologie 19